CN1298723C - Amorphous cephalosporin - Google Patents
Amorphous cephalosporin Download PDFInfo
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- CN1298723C CN1298723C CNB2004100276959A CN200410027695A CN1298723C CN 1298723 C CN1298723 C CN 1298723C CN B2004100276959 A CNB2004100276959 A CN B2004100276959A CN 200410027695 A CN200410027695 A CN 200410027695A CN 1298723 C CN1298723 C CN 1298723C
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- cefathiamidine
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- 229930186147 Cephalosporin Natural products 0.000 title claims description 4
- 229940124587 cephalosporin Drugs 0.000 title claims description 4
- 150000001780 cephalosporins Chemical class 0.000 title claims description 4
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- 229950005040 cefathiamidine Drugs 0.000 claims abstract description 88
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- 238000004108 freeze drying Methods 0.000 claims abstract description 22
- 239000007787 solid Substances 0.000 claims abstract description 22
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- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
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- 206010061695 Biliary tract infection Diseases 0.000 description 1
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- JFPVXVDWJQMJEE-QMTHXVAHSA-N Cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)C(=NOC)C1=CC=CO1 JFPVXVDWJQMJEE-QMTHXVAHSA-N 0.000 description 1
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- 206010040047 Sepsis Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241001312524 Streptococcus viridans Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
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- GCFBRXLSHGKWDP-XCGNWRKASA-N cefoperazone Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 GCFBRXLSHGKWDP-XCGNWRKASA-N 0.000 description 1
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- 229960002682 cefoxitin Drugs 0.000 description 1
- YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses an amorphous cefathiamidine solid expressed by an X-ray diffraction spectra, differential scanning (DSC) and infrared spectrum data. The solid can be prepared by a freeze-drying method, a spray-drying method and a precipitation method. The dissolving rate of the amorphous cefathiamidine is faster 4 to 5 times than that of crystallized products, and solvent residue of the amorphous cefathiamidine is greatly reduced. The present invention also relates to medical compositions containing the amorphous cefathiamidine and the application thereof.
Description
Technical field:
The present invention relates to a kind of non-crystalline state cynnematin, relate to the non-crystalline state solid substance of cefathiamidine specifically, and preparation method thereof and the application in pharmacy field.
Background technology:
Cynnematin is type of thermosensitive and bibulous beta-lactam antibiotics.Cephalosporin for injections is normally under aseptic condition, by the method preparation of solvent crystal.The cephalo product of crystal habit be it is generally acknowledged comparatively stable, and the physical aspect of product also has certain relation with its bioavailability, about the research of crystalline state and non-crystalline state aspect can be with reference to " solid state chemistry of drug ", 1982, PP10-11 and int, J, pharm, VO124, pp1-17.But the dissolution rate of crystalline state product in water is more amorphous usually slow, and solubleness is also relatively poor, and the non-crystalline state product shows better operability because its dissolution rate is fast in the clinical injection treatment.
More priorly be: the solvent crystal method because with an organic solvent generally can be residual in finished product.In the drug standard organic solvent residual there is strict requirement.One, two class organic solvents are to be subjected to strict restriction as methylene dichloride, DMF etc. in the pharmaceutical production; Even three kind solvents such as acetone, ethanol etc. also have strict controlling index.And the non-crystalline state product prepares owing to not passing through the solvent crystal method, so its dissolvent residual reduces greatly.
The method of the production non-crystalline state product that pharmaceutical industry is commonly used has freeze-drying, spray-drying process.Lyophilize is under low-temp low-pressure, a kind of drying means that the moisture in the material is directly distilled.Generally be that feed liquid is cooled to below the eutectic point (eutectic point), through elementary drying, secondary drying is removed residual moisture then, reclaims product at last.Usually in needs refrigerated feed liquid, add water miscible caffolding agent, as N.F,USP MANNITOL; Conditioning agent such as sodium-chlor, polyvalent alcohol (sorbic alcohol, lactose) etc. its objective is that to make freeze dried non-crystalline state powder mode of appearance good.Decomposition point is melted in this congruent melting that contains the solution of multiple composition, and might to melt decomposition point than the congruent melting of one-component low, and it is freezing, also corresponding prolongation time of drying, thereby increases cryodesiccated cost.
Spraying drying is to utilize nozzle that concentrated solution or suspension are sprayed into droplet, makes it be dried to the method for fine powder rapidly in warm air.
Lyophilize is specially adapted to the antibiotic preparation of thermo-sensitivity, and as cynnematin, and freeze dried Kefzol and cefoperazone are comparatively sophisticated cephalo products.
Cefathiamidine chemistry 7-N by name, N diisopropyl amidino groups sulfur acetyl Cephalosporanic acid inner salt.Its structure is as follows:
Be first-generation injection cephalo, antimicrobial spectrum is similar to cefoxitin, and is stronger to golden Portugal bacterium, Streptococcus viridans, pneumococcal effect, and faecalis is had unique anti-microbial activity.Be distributed widely in after the absorption in each organ, not metabolism in the body is mainly discharged by urine.Cefathiamidine is mainly used in respiratory tract infection due to golden Portugal bacterium, streptococcus pneumoniae and the suis, infection such as biliary tract infection, urinary tract infections, gynecological infection, septicemia, pneumonia, meningitis.Use crystallinity cefathiamidine sterilized powder clinically.
Summary of the invention:
The purpose of this invention is to provide a kind of non-crystalline state cefathiamidine solid substance.
Another object of the present invention provides the preparation method of non-crystalline state cefathiamidine solid substance, and comprising provides freeze-drying, spray-drying process and the precipitator method.
A further object of the present invention provides pharmaceutical composition and the application in treatment is anti-infective thereof that comprises this non-crystalline state cefathiamidine solid substance.
Non-crystalline state cefathiamidine solid substance is characterized in that it is to exist with the non-crystalline state solid substance that X-ray diffraction detects at least 90%.This solid substance can be characterized by:
1, characterizes with dsc (DSC), show that it is 146 ± 2 ℃ of obvious heat releases;
2, characteristic group's characteristic group's infrared absorption spectrum (KBr, cm
-1) data are 1231.8 ± 0.6,1339.3 ± 0.8,1392.1 ± 0.5,1608.5 ± 0.5,1774.5 ± 0.5.
3, fusion and decomposition point:＜128 ℃.
Non-crystalline state powder of the present invention records it 146 ± 2 ℃ of heat releases with DSC-1700 under nitrogen gas stream, thermal distortion occurs, and 157 ± 2 ℃ maximum peak occurs; Its enthalpy of phase change is about 240j/g.And crystal form cefathiamidine I shape is about 168 ℃, and heat release appears in crystal form II shape about 156 ℃, show their difference.
Described non-crystalline state cefathiamidine solid substance is characterized in that containing crystallite.
Another characterization parameter of non-crystalline state powder of the present invention is X-light powder diffraction spectrum, and is opposite with the crystallinity cefathiamidine, and X-light powdery diffractometry peak does not appear in the non-crystalline state cefathiamidine fully.
Described solid substance, the dissolution rate in the deionized water improves greatly than crystalline powder at normal temperatures.Under the same conditions, as 28 ℃ of room temperatures, accurately weighing non-crystalline state powder and crystallization shape powder are used the equivalent deionized water dissolving, measure the fast 4-5 of non-crystalline state powder dissolution speed ratio crystallization shape powder doubly.
The non-crystalline state cefathiamidine has identical physiological characteristics with the crystallinity cefathiamidine, and its every index meets standards of pharmacopoeia, and its dissolvent residual is significantly less than crystallinity product dissolvent residual.
Non-crystalline state cefathiamidine of the present invention is characterized in that being made by the freeze-drying method that contains the cefathiamidine one-component aqueous solution.This method comprises cefathiamidine is dissolved in the deionized water that cefathiamidine freeze-drying curve heating sublimation drying is pressed in sterile filtration behind the bleaching agent bleaching in freeze drier.
Described cefathiamidine can be a crystallization shape powder, also can be non-crystalline state, as the powder of the applicant at the disclosed two kinds of crystal habits of CN1462751A, CN1495187A, or its miscellany.
Because the low consolute temperature that the various ingredients of freezing feed liquid can make solution system changes when freezing with the characteristic of additive, particularly add the inorganic salt thing and can obviously reduce eutectic point (＜freezing and drying study association meeting〉22 phase 48-55 pages or leaves).If the low plait point of the main medicine aqueous solution is lower, add additive its fusing point is further reduced, this will cause lower freezing temp and longer time of drying, will directly influence its cryodesiccated economy.
Therefore the characteristics of freeze-drying of the present invention are to need not additive, adopt the single cefathiamidine aqueous solution, obtain lyophilized powder appearance effect preferably, and in freezing temp, have economy on time of drying.
The cryodesiccated characteristics of the present invention are that the proportioning of cefathiamidine and water is 5～60%, and are preferred 10～25%, and used discoloring agent is the activated carbon of activated processing, and its consumption is selected in 0～1% scope, and freezing temp is following 10～15 ℃ an of eutectic point.
Replenish as one of the present invention, in freezing feed liquid, add oxidation inhibitor such as phenylformic acid, halfcystine, sodium bisulfite etc. and obtain freeze-drying cefathiamidine composition.
Non-crystalline state cefathiamidine of the present invention is characterized in that the spray drying process that contains the cefathiamidine one-component aqueous solution makes.Cefathiamidine is configured to pharmaceutically required medicinal concentration, and decolouring is filtered, and degerming removes thermal source and makes according to the drying process with atomizing method.
The present invention is outside normal freeze-drying and spray drying process, discovery is passed through its deposition condition of control with the precipitator method, also can obtain the non-crystalline state powder, therefore, non-crystalline state cefathiamidine of the present invention, so its feature is also being made by intermediate processing, be about to cefathiamidine solution and in organic solvent, precipitate rapidly, separate dry and get.
Above-mentioned intermediate processing is characterised in that cefathiamidine is dissolved in preparation cefathiamidine solution in the mixed solvent of water or alcohol or water and alcohol that described alcohol is methyl alcohol, ethanol.Wherein organic solvent is for to dissolve each other with water or alcohol, and insoluble with cefathiamidine or sl. sol. solvent comprises C
1-4Alkyl ketone such as methylethylketone, acetone, butanone, isobutyl ketone etc., THF, acetonitrile.
Fast cefathiamidine solution is distributed in the precipitation agent, separates dry.Wherein stirring velocity is in 600～1000 rev/mins of scopes; The ratio of cefathiamidine and water and organic solvent is 1: 2～3: 40～100.
The present invention comprises that also the non-crystalline state cefathiamidine is preparing treatment by the application in the medicine of the infection due to the Gram-positive sensitive organism.
The invention provides a kind of composition of cephalosporin, it is characterized in that comprising the non-crystalline state cefathiamidine and the pharmaceutically acceptable carrier for the treatment of significant quantity.
Above-mentioned carrier can be various conditioning agents such as sodium-chlor, polyvalent alcohol such as lactose, sorbic alcohol, caffolding agent such as N.F,USP MANNITOL, oxidation inhibitor such as phenylformic acid, halfcystine, sodium bisulfite etc.These carriers can be formulated in the feed liquid before lyophilize or spraying drying, also can mix powder according to a certain ratio with the non-crystalline state cefathiamidine under aseptic condition, were distributed into each specification powder injection.
Described pharmaceutical composition is characterized in that injection.
Therefore the present invention also comprises a kind of injection powder pin that the non-crystalline state cefathiamidine is an activeconstituents that contains, and its specification has 0.5g, 1g, 2g or 5g, adds injection water dissolved dilution during clinical use and gets final product.
Non-crystalline state cefathiamidine of the present invention and crystallization shape cefathiamidine are except that physical aspect is different, have identical physiological characteristics, and very easily dissolving in water, under the same conditions, measure the fast 4-5 of non-crystalline state powder dissolution speed ratio crystallization shape powder doubly, this just brings convenience for clinical pharmacy.Take lyophilize and spray drying process owing to need not organic solvent, thereby this non-crystalline state product dissolvent residual is low, the finished product clarity is good, its dissolvent residual methylene dichloride is 0.01%, standards of pharmacopoeia is formulated by the crystal form powder, the residual index of its methylene dichloride is less than 0.06%, and therefore dissolvent residual index of the present invention is higher than standards of pharmacopoeia.Also can make the non-crystalline state powder with the precipitator method, this has just enriched prior art.The freeze-drying method of taking one-component helps energy efficient guaranteeing preferably can to finish freeze-drying process at comparatively high temps with in the short period under the dried frozen aquatic products outward appearance, shortens the operating time, has the industrialization cost advantage.
Figure of description
Accompanying drawing 1: non-crystalline state cefathiamidine dsc (DSC) curve, non-crystalline state powder record it 146 ± 2 ℃ of heat releases with DSC-1700 under nitrogen gas stream, thermal transition occurs.
Accompanying drawing 2: non-crystalline state cefathiamidine characteristic group infrared absorpting light spectra.
Accompanying drawing 3: non-crystalline state cefathiamidine x-ray diffraction collection of illustrative plates proves the non-crystalline state powder.
Accompanying drawing 4: the freeze-drying curve of cefathiamidine.
Specific embodiment:
Below the present invention is specifically described, but the present invention is not limited thereto.
Example 1: the preparation of lyophilization cefathiamidine.
Take by weighing 120 gram cefathiamidines, add 600ml precooling water for injection, the dissolving back claims 0.6g activated active C, sterile filtration behind the decolouring 10min in ice bath, bacteria-free filtrate places Freeze Drying Equipment (medical LGJ-LC shape Freeze Drying Equipment), presses that the cefathiamidine freeze-drying curve is freezing, heating, distillation, drying.Get white cefathiamidine powder, content 95.8%, related substance 1.08%, moisture 1.8%, residual 0.01% (standards of pharmacopoeia is less than 0.06%) of dichloromethane solvent, other index meets standards of pharmacopoeia.
Dsc (DSC) curve records it 147.74 ℃ of heat releases, and its fusion and decomposition point that the fusing point instrument is surveyed is 127 ℃,
Characteristic group's infrared absorption spectrum (KBr, cm
-1) be: 1231.8,1339.0,1392.2,1608.0,1774.6.
The x-ray diffraction collection of illustrative plates proves the non-crystalline state powder.
Dissolution rate is measured: 28 ℃, take by weighing 0.5g lyophilized powder and crystal powder respectively, and add 5ml water for injection, measure dissolution rate, lyophilized powder is molten clear at the 4.5th second, and crystal powder is molten clear at the 21st second.Lyophilized powder speed is 4.66 times of crystal powder.
The preparation of example 2, lyophilization cefathiamidine
Configuration concentration is 60% the cefathiamidine aqueous solution, adds 0.4gC decolouring, and other condition is with example 1, off-white powder, its content 96.02%, related substance 1.10%, moisture 1.7%, dichloromethane solvent is residual 0.01%, other index meets standards of pharmacopoeia.
Dsc (DSC) curve records it 147.20 ℃ of obvious heat releases, and it is 127 ℃ that the fusing point instrument records its fusion and decomposition point,
Characteristic group's infrared absorption spectrum (KBr, cm
-1) be: 1231.2,1338.6,1392.1,1607.9,1774.7.
The x-ray diffraction collection of illustrative plates proves the non-crystalline state powder.
Dissolution rate is measured as example 1, and lyophilized powder is molten clear at 4.3 seconds.
The preparation of example 3, lyophilization cefathiamidine
Configuration concentration is 10% the cefathiamidine aqueous solution, adds the 0.2gC decolouring, and other condition gets white powder with example 1.
Dsc (DSC) curve records it 146.9 ℃ of obvious heat releases, and the fusing point instrument shows that its fusion and decomposition point is 126～127 ℃,
Characteristic group's infrared absorption spectrum (KBr, cm
-1) be: 1231.9,1339.5,1393.9,1774.6.
The x-ray diffraction collection of illustrative plates proves the non-crystalline state powder.
Dissolution rate is measured as example 1, and lyophilized powder is molten clear at 5 seconds.
The preparation of example 4, lyophilization cefathiamidine
Take by weighing crystal form cefathiamidine 100g, it is water-soluble clear to add the 700ml injection, and 0.1gC decolouring back is by the method lyophilize of example 1, and the DCS of gained sample shows it 146.1 ℃ of obvious heat releases, and the fusion and decomposition point is 125 ℃, and x-ray diffraction is with example 1.
Example 5, spray drying method for preparation non-crystalline state cefathiamidine.
Take by weighing cefathiamidine and be configured to the aqueous solution of 15% concentration, decolouring is filtered, and degerming removes thermal source, evenly adds (BUCHI MODEL190) in the little shape spray-dryer, makes according to the drying process with atomizing method.Dried product X-ray diffraction proves non-crystalline state.
Example 6, the precipitator method prepare the non-crystalline state cefathiamidine.
Take by weighing cefathiamidine 2g and be dissolved in the 4ml water, low whipping speed is under 1000 rev/mins, and the aqueous solution is added drop-wise in the 100ml acetone, separate dry and the 1.4g product, DCS shows it 146.1 ℃ of obvious heat releases, X-ray diffraction is the non-crystalline state product.
Example 7, the precipitator method prepare the non-crystalline state cefathiamidine.
Take by weighing cefathiamidine 2g and be dissolved in 2ml methyl alcohol and the 3ml water, low whipping speed is under 800 rev/mins, with above-mentioned drips of solution be added to 200ml second fine in, separate dry and the 1.3g product, X-ray diffraction is the non-crystalline state product.
Example 8, the precipitator method prepare the non-crystalline state cefathiamidine.
Take by weighing cefathiamidine 2g and be dissolved in the 4ml water, low whipping speed is under 1000 rev/mins, and the aqueous solution is added drop-wise in the fine mixed solvent of 150ml acetone and second, separate dry and the 1.5g product, X-ray diffraction is the non-crystalline state product.
Characteristic group's infrared absorption spectrum (KBr, cm
-1) be: 1231.8,1339.2,1392.5,1774.5.
Dsc (DSC) curve shows it 145.2 ℃ of obvious heat releases, and the fusion and decomposition point is 120 ℃.
Example 9, preparation of compositions
Configuration 30% cefathiamidine solution in the phenylformic acid saturated aqueous solution, claim 0.6g activated active C, sterile filtration behind the decolouring 10min in ice bath, bacteria-free filtrate places Freeze Drying Equipment (medical LGJ-LC shape Freeze Drying Equipment), presses that the cefathiamidine freeze-drying curve is freezing, heating, distillation, drying.Get the cefathiamidine freeze-dried preparation, content 95.3%, related substance 1.12%, moisture 1.8%, residual 0.01% (standards of pharmacopoeia is less than 0.06%) of dichloromethane solvent, other index meets standards of pharmacopoeia.
Dsc (DSC) curve shows it 146.55 ℃ of obvious heat releases, and the fusion and decomposition point is 126～127 ℃,
Characteristic group's infrared absorption spectrum (KBr, cm
-1) be: 1231.5,1338.7,1394.2,1774.8.
The x-ray diffraction collection of illustrative plates proves the non-crystalline state powder.
Example 10, preparation of compositions
Configuration contains 30% the cefathiamidine aqueous solution of 3 gram sodium bisulfites, by the method lyophilize of example 1, the cefathiamidine freeze-dried preparation, content 95%, dissolvent residual 0.01%.
Dsc (DSC) curve shows it 147.62 ℃ of obvious heat releases, and the fusion and decomposition point is 125～126 ℃,
Characteristic group's infrared absorption spectrum (KBr, cm
-1) be: 1232.1,1342,1392,1770.1.
The x-ray diffraction collection of illustrative plates proves the non-crystalline state powder.
Example 11, preparation of compositions
The cefathiamidine solution of configuration 30% in the cysteine saturated aqueous solution by the method lyophilize of example 1, gets the cefathiamidine freeze-dried preparation.
Dsc (DSC) curve shows it 146.8 ℃ of obvious heat releases, and the fusion and decomposition point is 125～126 ℃,
Characteristic group's infrared absorption spectrum (KBr, cm
-1) be: 1230.2,1340.2,1392.3,1774.5.
The x-ray diffraction collection of illustrative plates proves the non-crystalline state powder.
Example 12, preparation of compositions
The cefathiamidine solution of configuration 30% in the cysteine saturated aqueous solution by the method spraying drying of example 4, gets the cefathiamidine spray dried formulations.
Dsc (DSC) curve shows it 146.9 ℃ of obvious heat releases, and the fusion and decomposition point is 125～126 ℃,
Characteristic group's infrared absorption spectrum (KBr, cm
-1) be: 1230.1,1340.3,1392.5,1774.0.
The x-ray diffraction collection of illustrative plates proves the non-crystalline state powder.
Example 13, contrast experiment
Configuration contains 30% the cefathiamidine aqueous solution of 3 gram N.F,USP MANNITOL, by the method lyophilize of example 1, the cefathiamidine freeze-dried preparation.
It is 94～96 ℃ that fusion and decomposition point instrument is measured its fusion and decomposition point,
Characteristic group's infrared absorption spectrum (KBr, cm
-1) be: 1231.4,1339.1,1394.7,1774.2.
The x-ray diffraction collection of illustrative plates proves the non-crystalline state powder.
Claims (9)
1. non-crystalline state cefathiamidine solid substance, its feature at least 90% is to exist with the non-crystalline state solid substance, also contains crystallite, this solid substance can be characterized by:
(1), dsc shows that it is 146 ± 2 ℃ of heat releases;
(2), characteristic group's KBr compressing tablet infrared absorption spectrum data are 1231.8 ± 0.6cm
-1, 1339.3 ± 0.8cm
-1, 1392.1 ± 0.5cm
-1, 1608.5 ± 0.5cm
-1, 1774.5 ± 0.5cm
-1
(3), fusion and decomposition point:＜128 ℃.
2. according to the preparation method of the non-crystalline state cefathiamidine solid substance of claim 1, it is characterized in that making by the freeze-drying method that contains the cefathiamidine one-component aqueous solution.
3. according to the preparation method of the non-crystalline state cefathiamidine solid substance of claim 1, it is characterized in that making by the spray drying process that contains the cefathiamidine one-component aqueous solution.
4. according to the preparation method of the non-crystalline state cefathiamidine solid substance of claim 1, its feature also is cefathiamidine solution is being dissolved each other with water or alcohol rapidly, and precipitates in insoluble with cefathiamidine or the sl. sol. organic solvent, separates dry and gets.
5. the preparation method of the described non-crystalline state cefathiamidine of claim 4 solid substance is characterized in that cefathiamidine is dissolved in water, methyl alcohol, ethanol or water and methyl alcohol, alcoholic acid mix preparation cefathiamidine solution in the solvent.
6. the preparation method of the described non-crystalline state cefathiamidine of claim 4 solid substance, wherein organic solvent is C
3-4Alkyl ketone, tetrahydrofuran (THF), acetonitrile.
7. the described non-crystalline state cefathiamidine of claim 1 solid substance is treated by the application in the medicine of the infection due to the Gram-positive sensitive organism in preparation.
8. composition of cephalosporin is characterized in that comprising the non-crystalline state cefathiamidine solid substance and the pharmaceutically acceptable carrier of the claim 1 for the treatment of significant quantity.
9. the described pharmaceutical composition of claim 8 is characterized in that injection.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100276959A CN1298723C (en) | 2004-06-18 | 2004-06-18 | Amorphous cephalosporin |
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|---|---|---|---|
| CNB2004100276959A CN1298723C (en) | 2004-06-18 | 2004-06-18 | Amorphous cephalosporin |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3646025A (en) * | 1969-10-30 | 1972-02-29 | Bristol Myers Co | 7-(alpha-(1 3-substituted amidino-2-thio)acetamido)cephalosporanic acids |
| CN1385434A (en) * | 2002-06-10 | 2002-12-18 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Method for making cefathiamidine crystal |
| CN1462751A (en) * | 2002-06-10 | 2003-12-24 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Method for preparing crystalline cefathiamidine and its usage |
-
2004
- 2004-06-18 CN CNB2004100276959A patent/CN1298723C/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3646025A (en) * | 1969-10-30 | 1972-02-29 | Bristol Myers Co | 7-(alpha-(1 3-substituted amidino-2-thio)acetamido)cephalosporanic acids |
| CN1385434A (en) * | 2002-06-10 | 2002-12-18 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Method for making cefathiamidine crystal |
| CN1462751A (en) * | 2002-06-10 | 2003-12-24 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Method for preparing crystalline cefathiamidine and its usage |
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