CN102816174A - Amorphous cefmenoxime hydrochloride compound - Google Patents
Amorphous cefmenoxime hydrochloride compound Download PDFInfo
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- CN102816174A CN102816174A CN2012103327270A CN201210332727A CN102816174A CN 102816174 A CN102816174 A CN 102816174A CN 2012103327270 A CN2012103327270 A CN 2012103327270A CN 201210332727 A CN201210332727 A CN 201210332727A CN 102816174 A CN102816174 A CN 102816174A
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Abstract
The invention belongs to the technical field of medicines and particularly relates to an amorphous cefmenoxime hydrochloride compound which is measured by a powder diffraction measurement method, and does not have a remarkable characteristic diffraction peak in X-ray powder diffraction pattern expressed by the diffraction angle of 2 theta+/-0.2 degree. The amorphous cefmenoxime hydrochloride compound has the characteristic of high dispersity, is beneficial to medicament absorption, and can be used for improving the clinical adaptability. The amorphous cefmenoxime hydrochloride compound is yellowish amorphous powder, and does not have or slightly has special smell. The amorphous cefmenoxime hydrochloride compound can be easily dissolved in dimethyl sulfoxide and dimethyl formamide, can be dissolved in water and is slightly soluble in alcohol. The amorphous cefmenoxime hydrochloride compound provided by the invention is high in purity and good in stability, and is not obvious in moisture absorption and weight increment even under the condition of high humidity, so that related substances are not increased; and compared with cefmenoxime hydrochloride with other crystalline states, the amorphous cefmenoxime hydrochloride compound has high solubility.
Description
Technical field
The present invention relates to the medicine in the field of medicaments, especially relate to a kind of unformed cefmenoxime hydrochloride compound.
Background technology
Cefmenoxime is the semisynthetic cephalosporins Broad spectrum antibiotics of the third generation, reaches germicidal action through the biosynthesizing that suppresses bacteria cell wall.In vitro tests shows that these article all have effect to gram-positive microorganism and negative bacterium.It is because the permeability of its pair cell adventitia is good and stable to β-Nei Xiananmei that these article have strong anti-microbial effect to Gram-negative bacteria; And the avidity to penicillin-binding protein (PBPs) 1A, 1B and 3 is strong, thereby pair cell wall mucopeptide is cross-linked to form and has stronger inhibition.
Cefmenoxime Hemihydrochloride
English name: Cefmenoxime Hydrochloride;
Chemical name: (6R, 7R) – 7-[(Z) – 2 – (2-amino-4-thiazolyl)-2-methoxyimino kharophen]-3-[[1-methyl isophthalic acid H-tetrazolium-5-yl)-sulphur] methyl]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-formate hydrochlorate (2:1);
Molecular formula: (C
16H
17N
9O
5S
3)
2HC1;
Molecular weight: 1059.58;
Chemical property: white or little yellow crystalline powder; No tool or special odor is arranged slightly.Be soluble in methyl-sulphoxide, N, be not soluble in methyl alcohol, the utmost point is insoluble in water, is dissolved in ethanol and acetone hardly.
Structural formula:
Indication: these article are applicable to the following infection disease that the responsive streptococcus (except the faecalis) of cefmenoxime, streptococcus pneumoniae, Peptococcus, Peptostreptococcus, intestinal bacteria, Citrobacter, Klebsiella, enterobacter, Serratia, proteus, hemophilus influenzae, Bacteroides etc. cause:
1, the secondary infection of pneumonia, bronchitis, bronchiectasis concurrent infection, chronic respiratory system diseases; Pulmonary abscess, pyothorax;
2, pyelonephritis, urocystitis; Bartholinitis, endometritis, adnexitis, pelvic inflammatory disease, parametritis;
3, cholangitis, cholecystitis, liver abscess, peritonitis;
4, the secondary infection of burn, operation wound;
5, septicemia;
6, meningitis;
Usage: these article are dissolved in 0.9% sodium chloride injection or the glucose injection, intravenous drip.
The grownup also can be added on 1 consumption 0.5g-2g of these article in the fluid infusion such as liquid glucose, electrolyte solution or amino acid preparation, in 30 minutes-2 hours, carry out intravenous drip.Also can consider 1 consumption is added in the fluid infusion to children's,, carry out intravenous drip at 30 minutes-1 hour.Quiet notes inject about 5ml lysate during with 1g and in bottle, dissolve, and the injection of dissolving back is no less than the 100ml lysate and instils.
Consumption:
1, adult: low-grade infection: 1-2g on the one, divide 2 intravenous drips; In, severe infection: can increase to 4g on the one, divide 2-4 intravenous drip, also can carry out dose titration according to clinical setting.
2, children's: low-grade infection: per kilogram of body weight 40-80mg on the one, divide 3-4 intravenous drip; In, severe infection: can increase to per kilogram of body weight 160mg on the one, divide 3-4 intravenous drip; Meningitis: but increment to day per kilogram of body weight 200mg divides 3-4 intravenous drip.
Genotoxicity: animal experiment shows that in the administration organogenetic period of rat, rabbit and monkey, the dead or miscarriage of doe all appears in each administration group of rabbit, but various animal does not all see teratogenesis.The general reproductive toxicity test of rat, perinatal period, reproductive toxicity test was not all seen obviously unusual.
Pharmacological action: these article are semisynthetic cephalosporins Broad spectrum antibiotics, reach germicidal action through the biosynthesizing that suppresses bacteria cell wall.It is because it has the good cell outer membrane permeability that these article have strong anti-microbial effect to Gram-negative bacteria; Stable to β-Nei Xiananmei; And the avidity to penicillin-binding protein (PBPs) 1A, 1B and 3 is strong, thereby pair cell wall mucopeptide is cross-linked to form and has stronger inhibition.In vitro tests shows that these article all have effect to gram-positive microorganism and negative bacterium.To the antimicrbial power of gram-positive microorganism, with micrococcus scarlatinae and streptococcus pneumoniae and opinion, effect is better than cefotiam (CTM) and Kefzol (CEZ).Peptococcus, Peptostreptococcus are shown strong antimicrbial power.To the antimicrbial power of Gram-negative bacteria, with intestinal bacteria and pneumobacillus and opinion is better than CTM slightly, far be better than CEZ.Antimicrbial power to hemophilus influenza, proteus, emplastic serratia, citrobacter genus, enteron aisle Pseudomonas is stronger than CTM, and is strong more than CEZ.In addition Bacteroides is also shown strong antimicrbial power.
Pharmacokinetics: according to documents and materials; Behind renal function normal adult single intravenous drip this medicine 0.5g and the 1g; The blood peak concentration of drug can reach 50.9mg/L and 135.7mg/L respectively, and behind single intravenous injection cefmenoxime 0.5g and the 1g, the blood peak concentration of drug can be 75mg/L and 125mg/L respectively.The serum elimination transformation period of these article is about 1 hour.It is good in multiple tissue and body fluid, to distribute after the administration.Also can see through hemato encephalic barrier.This medicine is mainly through RE, behind an intravenous injection of grownup (the normal person of renal function) or this medicine of intravenous drip 0.5g, 1g, the 2g, in 6 hours in the urine excretion rate be 60-82%.In addition, the urine drug level behind the intravenous drip 1g is 0-2 hour about 4400 μ g/L, 2-4 hour about 750 μ g/L, 4-6 hour about 120 μ g/L.Behind an intravenous injection of children's (the normal person of renal function) or intravenous drip 10,20, the 40mg/kg, 6 hours homaluria rate is identical with the grownup.
Application number is that the invention of CN201110040597.9 relates to pharmacy field, relates in particular to Cefmenoxime Hemihydrochloride micro mist and preparation method thereof and device.The Cefmenoxime Hemihydrochloride micro mist, the granularity of Cefmenoxime Hemihydrochloride micro mist is greater than 400 orders.The above-mentioned micronized method of Cefmenoxime Hemihydrochloride raw material, this method comprise the steps: dried Cefmenoxime Hemihydrochloride crystalline powder raw material, in micronizer mill, quicken back collision and pulverizing each other with supersonic airstream; Described supersonic airstream is the compressed-air actuated force by 0.4 ~ 0.8MPa, compressed-air actuated temperature≤40 ℃; Pulverized material gets into graded region with air-flow, and the material that meets granularity requirements is through configuring the grading wheel of rotating speed, and the material that does not meet granularity requirements returns pulverizes district's continuation pulverizing; The described material that meets granularity requirements is meant that granularity is greater than 500 orders.
Application number is that the invention of CN201010130555.X relates to a kind of cefmenoxime hydrochloride compound; Through acid-base reaction, charcoal absorption and preparative hplc separation and purification; Reach the purpose of refining purifying; Finally obtain highly purified cefmenoxime hydrochloride compound, optimized quality product, ensured safety of clinical administration.
Application number is that the invention of CN201110320076.9 relates to a kind of cefmenoxime hydrochloride in compound; Described cefmenoxime hydrochloride compound is a crystal; The X-ray powder diffraction that uses the Cu-K alpha-ray to measure is 6.0 °, 7.4 °, 11.0 °, 12.2 °, 17.5 °, 19.8 °, 21.6 ° at 2 θ; 24.8 ° and 27.7 ° show characteristic peak, the crystal master granularity of described Cefmenoxime Hemihydrochloride is that main granularity is 30～45 μ m, distribution density is 25～75 μ m.
Application number is that the invention of CN201110197613.5 relates to a kind of new preparation method that comprises the cefmenoxime hydrochloride compound of following treatment step: step 1) adds the Cefmenoxime Hemihydrochloride insoluble solvent in the raw material Cefmenoxime Hemihydrochloride; Controlled temperature is no more than 30 ℃; Vigorous stirring; Filter then, filter cake is no more than 20 ℃ Cefmenoxime Hemihydrochloride insoluble solvent with temperature and washs, and vacuum-drying or air dry; Step 2) filter cake is put into ammoniacal liquor, mild stirring, control pH value is no more than 9, obtains the ammonia soln of cefmenoxime acid, then the throw out of separating out is filtered out; Step 3) slowly adds concentration in the ammonia soln of cefmenoxime acid be the hydrochloric acid of 0.5-4mol/L, and temperature is controlled at 30-60 ℃, and final pH is controlled at 0.5-3.0; Kept 30 minutes to 5 hours, and slowly had crystal to separate out, progressively temperature is reduced to minimum 10 ℃ then; Leave standstill crystallization; Suction filtration, vacuum-drying gets the Cefmenoxime Hemihydrochloride elaboration; The crystalline mother solution that step 4) is optional will be separated out after the crystallization returns step 3).
Application number is the compsn that the invention of CN201110320077.3 relates to a kind of cefmenoxime hydrochloride in, the consisting of of described compsn: Cefmenoxime Hemihydrochloride 10 weight parts, soda ash light 1.5 ~ 2.5 weight parts; Preferred Cefmenoxime Hemihydrochloride 10 weight parts, soda ash light 1.75 ~ 1.8 weight parts; Described cefmenoxime hydrochloride compound is a crystal; The X-ray powder diffraction that uses the Cu-K alpha-ray to measure is 6.0 °, 7.4 °, 11.0 °, 12.2 °, 17.5 °, 19.8 °, 21.6 ° at 2 θ; 24.8 ° and 27.7 ° show characteristic peak; The crystal master granularity of described Cefmenoxime Hemihydrochloride is that main granularity is 30 ~ 45 μ m, and distribution density is 25 ~ 75 μ m.
Application number is that the CN201110060475.6 invention relates to a kind of novel method for preparing Cefmenoxime Hemihydrochloride.This method is starting raw material with 7-ATCA.HCl, carries out acylation reaction with the AE-active ester and generates 7-[α-(thiazolamine-4-yl)-Z-2-methoxyimino acetamido]-3-cephem-4-carboxylic acid, and Cefmenoxime Hemihydrochloride is given birth in last and hydrochloric acid effect.Present method is simple to operate, and yield is high, shortens the process time widely, very easily is beneficial to suitability for industrialized production, and the Cefmenoxime Hemihydrochloride steady quality of this method preparation, and product look level and water impurity on average are superior to other method.
Application number is that the invention of CN201010127287.6 provides a kind of Cefmenoxime Hemihydrochloride/anhydrous sodium carbonate medicinal composition lipidosome injection and method for making thereof; Described Cefmenoxime Hemihydrochloride liposome/anhydrous sodium carbonate medicinal composition is characterized in that being made up of the following component of calculating by mass parts: 1 part of Cefmenoxime Hemihydrochloride, soda ash light 0.36-0.44 part, 1 ~ 3 part of liposome matrix, 0 ~ 1 part of additives.
Application number be CN200910114629.8 disclosure of the Invention a kind of preparation technology of instantly-dissolving cefmenoxime hydrochloride, may further comprise the steps: 1) get the Cefmenoxime Hemihydrochloride bullion and add the water formulated suspension, add yellow soda ash and make its dissolving, clear liquor; 2) clear liquor is used activated carbon decolorizing, and washing merges washing lotion, gets solution A; 3) using the pH value of hydrochloric acid conditioning solution A is 0.8～1.2, filters, and collects filtrating, gets solution B; 4) using the pH value of weakly alkaline solution regulator solution B is 1.3～1.75, stirred crystallization, and the complete after-filtration of crystallization, washing, vacuum-drying promptly gets.
Application number be CN201210059072.4 disclosure of the Invention a kind of method for preparing aseptic cefmenoxime hydrochloride compound.This method is a starting raw material to be prone to purchasing raw material 7-ACT.HCL on the market; Carry out condensation reaction with active ester (AE) and generate 7-[α-(thiazolamine-4-yl)-Z-2-methoxyimino acetamido]-3-(1-methyl isophthalic acid H-5-tetrazyl-thiomethyl)-3-cephem-4-carboxylic acid sodium salt (being the cefmenoxime sodium salt), last and 10% hydrochloric acid effect generates Cefmenoxime Hemihydrochloride.
Application number is that the invention of CN200810163511.X provides a kind of cefmenoxime hydrochloride in preparation, and major ingredient comprises injection soybean phospholipid, SUV, cefmenoxime, and its weight ratio is a soybean phospholipid: SUV: cefmenoxime is 10-2: 4-1: 1.Through getting soybean phospholipid and SUV, add anhydrous alcohol solution, pass through 0.8 μ m millipore filtration twice after the abundant aquation of adding damping fluid; Make blank liposome; Add cefmenoxime and NaHCO3 solution again, add water for injection behind the mixing, be incubated in the water-bath; With the cold water cooling, get the cefmenoxime Liposomal formulation immediately.
The contriver is through lot of test, and to the analysis and the structural identification of gained sample, accident has obtained a kind of cefmenoxime hydrochloride compound of unformed shape, and purity is high, and total impurities is no more than 0.08%; Good stability is even the moisture absorption weightening finish is also not obvious under high humidity; Related substance does not increase; Dissolving is rapid, the injection good stability that makes.
Summary of the invention
One object of the present invention discloses a kind of unformed cefmenoxime hydrochloride compound.
Another object of the present invention discloses the preparation method of cefmenoxime hydrochloride compound.
Combine the object of the invention that content of the present invention is specifically described at present.
The unformed cefmenoxime hydrochloride compound structural formula of the present invention is following:
It is characterized in that:
Molecular formula: (C
16H
17N
9O
5S
3)
2HC1;
Molecular weight: 1059.58;
Chemical property: the unformed powder of little yellow; No tool or special odor is arranged slightly.Be soluble in methyl-sulphoxide, N, in water, dissolve, slightly be dissolved in ethanol.
Polystyrene film was used in the correction of instrument when infrared spectrogram was measured, and met the regulation of Chinese Pharmacopoeia.This unformed cefmenoxime hydrochloride compound infrared spectrogram (KBr pressed disc method mensuration) is at 1785 ± 5cm
-11645 ± 5cm
-11568 ± 5cm
-11374 ± 5cm
-11342 ± 5cm
-11274 ± 2cm
-11100 ± 2cm
-11042 ± 2cm
-1There is characteristic peak at the place, sees Fig. 2.Limit of error is confirmed according to Pharmacopoeia of People's Republic of China (2010 editions, two ones) appendix IV C-infrared spectrophotometry.
Cefmenoxime hydrochloride compound adopts D/Max-2500.9161 type x-ray diffractometer to measure condition determination: Cu Ka target, tube voltage 40KV, tube current 100mA.With its powder X-ray diffraction collection of illustrative plates of 2 θ ± 0.2 °, see Fig. 3.
Showing among Fig. 3 that this cefmenoxime hydrochloride compound does not have the obvious characteristic absorption peak, is amorphous state, and amorphous state is a kind of form that there is heteromorphism in material, also is a kind of special crystal formation state.
Another object of the present invention discloses the preparation method of unformed cefmenoxime hydrochloride compound, it is characterized in that comprising the following steps: bullion 50g, deionized water 2.5L and ethanol 2.5L are put in the reaction flask, is heated with stirring to the solution clarification; Slowly be cooled to 60-70 ℃, insulated and stirred 1 hour slowly is cooled to 30-40 ℃ then, stirs 1 hour; Be cooled to 10-20 ℃ again, stirred suction filtration 2 hours; Filter cake is washed with an amount of bubble, gets the solid matter oven dry, gets Cefmenoxime Hemihydrochloride white powder 44.5g; Yield 89%, chemical purity are up to 99.9%, and total impurities is less than 0.08%.
Used Cefmenoxime Hemihydrochloride, the method that provides according to document US 4098888 is synthetic, the chemical structure of synthetic Cefmenoxime Hemihydrochloride through proton nmr spectra (
1H-NMR), ultimate analysis proves that chemical structure is correct.
Compared with prior art, the present invention has following advantage:
1) cefmenoxime hydrochloride compound provided by the present invention is the unformed shape cefmenoxime hydrochloride compound, possesses the polymolecularity characteristics, helps drug absorption, improves clinical flexibility.
2) cefmenoxime hydrochloride compound purity provided by the present invention is high, good stability, even the moisture absorption weightening finish is also not obvious under high humidity, related substance does not increase; Cefmenoxime Hemihydrochloride solubleness than other crystalline state is high.
3) unformed cefmenoxime hydrochloride compound provided by the present invention is for the market risk of the yield that improves this product, reduction product, and better application has very big help in clinical treatment.
4) unformed cefmenoxime hydrochloride compound provided by the present invention proves constant product quality through industrialized production and study on the stability, and through pharmacology, toxicological test, solution is non-stimulated to blood vessel, and no anaphylaxis does not have haemolysis yet, and human body is not had injury.
5) preparation method of unformed cefmenoxime hydrochloride compound provided by the present invention, this method is simple, prepared cefmenoxime hydrochloride in good stability.
Figure of description:
Fig. 1, the chemical structural drawing of cefmenoxime hydrochloride compound;
Fig. 2, the infrared spectrogram of cefmenoxime hydrochloride compound;
Fig. 3, the powder diffraction spectrum of cefmenoxime hydrochloride compound.
Embodiment:
Below in conjunction with embodiment the present invention is done further explanation, make this area professional and technical personnel better understand the present invention.It is indicative that embodiment is merely, and means that never it limits scope of the present invention by any way.
Embodiment 1
Bullion 50g, deionized water 2.5L and ethanol 2.5L are put in the reaction flask, be heated with stirring to the solution clarification, slowly be cooled to 60-70 ℃, insulated and stirred 1 hour; Slowly be cooled to 30-40 ℃ then, stirred 1 hour, be cooled to 10-20 ℃ again, stirred 2 hours; Suction filtration, filter cake is washed with an amount of bubble, gets the solid matter oven dry, gets Cefmenoxime Hemihydrochloride white powder 44.5g; Yield 89%, chemical purity are up to 99.9%, and total impurities is less than 0.08%, and the moisture that uses the karl Fischer method to record is 0.17%.
The infrared spectrogram of this compound is seen Fig. 2, uses the KBr compressing tablet during mensuration.
The X-ray diffractogram of this compound is seen Fig. 3.Instrument model and condition determination: Japanese D/max2500 type diffractometer of science; CuKa 40Kv 100mA; 2 θ sweep limit: 0-50 °.
Bullion 50g, deionized water 4L and ethanol 4L are put in the reaction flask, be heated with stirring to the solution clarification, slowly be cooled to 60-70 ℃, insulated and stirred 1 hour; Slowly be cooled to 30-40 ℃ then, stirred 1 hour, be cooled to 10-20 ℃ again, stirred 2 hours; Suction filtration, filter cake is washed with an amount of bubble, gets the solid matter oven dry, gets Cefmenoxime Hemihydrochloride white powder 45.5g; Yield 91%, chemical purity are up to 99.9%, and total impurities is less than 0.08%, and the moisture that uses the karl Fischer method to record is 0.19%.
Test Example 1
The ultimate analysis experiment
So the result finds out from the primitive element analytical test: C, H, N, S, Cl test value match with theoretical value.
Test Example 2
Solubility test
Test method(s): except as otherwise herein provided, take by weighing the trial-product (embodiment 1) that is ground into fine powder, place the solvent of 25 ℃ ± 2 ℃ of one constant volume, every at a distance from 5 minutes 30 seconds of powerful jolting; Observe the dissolving situation in 30 minutes, as when cannot see particles of solute or drop, promptly be regarded as dissolving fully.
Very easily dissolving means that solute 1g (ml) can dissolve in less than 1ml at solvent;
Yi Rong means that solute 1g (ml) can dissolve in solvent 1～less than 10ml;
Dissolving means that solute 1g (ml) can dissolve in solvent 10～less than 30ml;
Slightly dissolve and mean that solute 1g (ml) can dissolve in solvent 30～less than 100ml;
Slightly soluble means that solute 1g (ml) can dissolve in solvent 100～less than 1000ml;
Soluble,very slightly means that solute 1g (ml) can dissolve in solvent 1000～less than 10000ml;
The almost insoluble or insoluble solute 1g (ml) that means can not dissolve in solvent 10000ml fully.
The solubility test result
Conclusion: be soluble in methyl-sulphoxide, N, in water, dissolve, slightly be dissolved in ethanol.
Test Example 3
Stability test
The contriver studies the chemicalstability of cefmenoxime hydrochloride compound of the present invention (embodiment 1); The investigation condition is high temperature (60 ℃ ± 2 ℃), illumination (4500Lx ± 500lx); (92.5%, RH) investigate index is outward appearance, content and related substance to high humidity.
| The condition determination time | Content (%) | Total impurities (%) | Outward appearance |
| Illumination 0 day | 99.95 | 0.03 | White powder |
| Illumination 5 days | 99.92 | 0.04 | |
| Illumination | |||
| 10 days | 99.91 | 0.05 | White powder |
| High temperature 0 day | 99.95 | 0.03 | White powder |
| High temperature 5 days | 99.90 | 0.04 | White powder |
| |
99.90 | 0.05 | White powder |
| High humidity 0 day | 99.95 | 0.03 | White powder |
| High humidity 5 days | 99.91 | 0.04 | White powder |
| |
99.89 | 0.05 | White powder |
The result: under illumination, high temperature, super-humid conditions from 0-10 days, outward appearance, related substance, content do not change, and explains that chemicalstability is good, the manufacturing and the standing storage of suitable pharmaceutical prepn.
Test Example 4
At 40 ℃, under different relative humidity (RH) conditions (75%), the mensuration of moisture in the Cefmenoxime Hemihydrochloride (embodiment 1):
The result: at 40 ℃, under different relative humidity (RH) conditions (75%), moisture does not almost have influence, and explanation has good stability, and is fit to the manufacturing and the standing storage of pharmaceutical prepn.
Claims (4)
1. a kind of unformed cefmenoxime hydrochloride compound shown in the formula I,
It is characterized in that: described cefmenoxime hydrochloride compound is measured with the powdery diffractometry assay method, and the X-ray powder diffraction collection of illustrative plates of representing with 2 θ ± 0.2 ° diffraction angle does not have the notable feature diffraction peak.
2. cefmenoxime hydrochloride compound according to claim 1 is characterized in that: infrared spectrogram, and pellet technique is measured, at 1785 ± 5cm-1; 1645 ± 5cm-1; 1568 ± 5cm-1; 1374 ± 5cm-1; 1342 ± 5cm-1; 1274 ± 2cm-1; There is characteristic peak at 1100 ± 2cm-1,1042 ± 2cm-1 place.
3. cefmenoxime hydrochloride compound according to claim 1 is characterized in that: cefmenoxime hydrochloride compound is the unformed powder of little yellow; No tool or special odor is arranged slightly.Be soluble in methyl-sulphoxide, N, in water, dissolve, slightly be dissolved in ethanol.
4. the preparation method of cefmenoxime hydrochloride compound according to claim 1 is characterized in that comprising the following steps: bullion 50g, deionized water 2.5L and ethanol 2.5L are put in the reaction flask, is heated with stirring to the solution clarification, slowly is cooled to 60-70 ℃; Insulated and stirred 1 hour slowly is cooled to 30-40 ℃ then, stirs 1 hour; Be cooled to 10-20 ℃ again, stirred suction filtration 2 hours; Filter cake is washed with an amount of bubble, gets the solid matter oven dry, gets Cefmenoxime Hemihydrochloride white powder 44.5g; Yield 89%, chemical purity are up to 99.9%, and total impurities is less than 0.08%.
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| CN103083322B (en) * | 2013-02-04 | 2014-04-16 | 海南中元堂医药科技有限公司 | Medicinal composition containing injection cefmenoxime hydrochloride and compound amino acid injection |
| CN103446158A (en) * | 2013-09-06 | 2013-12-18 | 海南美兰史克制药有限公司 | Pharmaceutical composition of cefmenoxime hydrochloride and pediatric compound amino acid injection |
| CN103446158B (en) * | 2013-09-06 | 2015-01-07 | 海南美兰史克制药有限公司 | Pharmaceutical composition of cefmenoxime hydrochloride and pediatric compound amino acid injection |
| CN105001239A (en) * | 2015-05-28 | 2015-10-28 | 浙江长典医药有限公司 | Cefmenoxime hydrochloride compound entity used for children and preparation thereof |
| CN106543019A (en) * | 2016-11-10 | 2017-03-29 | 聊城大学 | A kind of preparation method of anhydrotetracycline amorphous article |
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