CN114601805A - Cefminox sodium powder for injection and preparation method thereof - Google Patents
Cefminox sodium powder for injection and preparation method thereof Download PDFInfo
- Publication number
- CN114601805A CN114601805A CN202210038198.7A CN202210038198A CN114601805A CN 114601805 A CN114601805 A CN 114601805A CN 202210038198 A CN202210038198 A CN 202210038198A CN 114601805 A CN114601805 A CN 114601805A
- Authority
- CN
- China
- Prior art keywords
- cefminox sodium
- mass
- water
- injection
- cefminox
- 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.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses cefminox sodium powder for injection and a preparation method thereof, which improve a load carrier and macroporous resin through a novel purification process, effectively improve the content of cefminox while ensuring the yield, reduce the content of insoluble particles and bacterial endotoxin, and improve the injection compliance.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to cefminox sodium powder for injection and a preparation method thereof.
Background
Cefminox sodium is a third-generation cephalosporin developed by Nippon Mingzhi fruit company in 1987 and is widely used in China. Cefminox has broad-spectrum antibacterial activity on gram-positive bacteria and gram-negative bacteria, and especially has strong antibacterial effect on Escherichia coli, Klebsiella, Haemophilus influenzae, Proteus and Bacteroides fragilis. The action mechanism is that the penicillin binding protein at the common action point of the beta-lactam antibiotics shows strong affinity, can inhibit cell wall synthesis, is combined with peptidoglycan, inhibits the combination of the peptidoglycan and lipoprotein to promote bacteriolysis, and shows strong bactericidal power in a short time. The cefminox sodium is suitable for respiratory system infection, urinary system infection, abdominal cavity infection, pelvic cavity infection and septicemia caused by sensitive bacteria.
The product has large clinical dosage, definite curative effect and good market prospect. The product is the same as most cephalosporin antibiotics, and the preparation is prepared by aseptic split charging of cefminox sodium raw material. When the cefminox sodium powder injection is injected, the injection part is easy to generate burning sensation.
Disclosure of Invention
The invention discloses cefminox sodium powder for injection and a preparation method thereof, which effectively improve the content of cefminox, reduce the content of insoluble particles and bacterial endotoxin and improve the injection compliance through a purification process.
A cefminox sodium powder injection is prepared by the following purification processes:
(1) dispersing a certain amount of hydroxypropyl distarch phosphate in water with the mass multiple of 3-5, then sequentially adding tributyl phosphate accounting for 1% of the mass of the hydroxypropyl distarch phosphate and histidine accounting for 6-8% of the mass of the hydroxypropyl distarch phosphate, emulsifying and dispersing, then adding epoxy chloropropane accounting for 1-2% of the mass of the hydroxypropyl distarch phosphate, uniformly dispersing, adjusting the system to be alkaline, heating to 50-55 ℃, reacting for 3-5 h, cooling and filtering, and washing for 3-5 times with water to obtain dry powder;
(2) dissolving a cefminox sodium crude product in a mixed solvent with the mass ratio of dichloromethane to ethanol to water being 2-3: 1: 0.3-0.5 being 3-5 times, adding the dry powder prepared in the step (1) with the mass ratio of cefminox sodium being 2-3 times after complete dissolution, and distilling the solvent under reduced pressure after full adsorption to prepare a loaded dry powder;
(3) taking macroporous resin BS-30 with the mass 20-30 times that of the loaded dry powder prepared in the step (2), dispersing the macroporous resin BS-30 in water, sequentially adding 1-2% of sucrose stearate and 0.3-0.5% of KH-792 coupling agent by mass of the resin, adjusting the system to be acidic, reacting for 1-2 h, washing for 3-5 times by using water, and then loading on a column to obtain a chromatographic column;
(4) placing the loaded dry powder prepared in the step (2) on the upper layer of a chromatographic column, firstly taking an ethanol water solution with the volume ratio of 40-50% as a mobile phase, and discarding a chromatographic solution until cefminox sodium begins to be chromatographed; then replacing an ethanol water solution with the volume ratio of 5-10% as a mobile phase, and collecting a chromatographic solution until the cefminox sodium is completely chromatographed; and (4) freezing and drying the collected chromatographic solution to obtain a pure cefminox sodium product.
Further, the vacuum distillation process in the step (2) comprises the following steps: the temperature is 35-40 ℃, and the vacuum degree is-0.09 MPa to-0.095 MPa.
The prepared pure cefminox sodium product can be subpackaged into 0.5g or 1.0g cefminox sodium powder for injection.
The invention has the advantages that: according to the invention, through a purification process, the content of cefminox is effectively increased, the content of insoluble particles and bacterial endotoxin is reduced, and the injection compliance is improved.
Detailed Description
Example 1
A cefminox sodium powder injection is prepared by the following purification processes:
(1) dispersing a certain amount of hydroxypropyl distarch phosphate in water with the mass multiple of 3, then sequentially adding tributyl phosphate and histidine with the mass being 1% of that of the hydroxypropyl distarch phosphate, emulsifying and dispersing, then adding epoxy chloropropane with the mass being 1% of that of the hydroxypropyl distarch phosphate, uniformly dispersing, adjusting the system to be alkaline, heating to 50 ℃, reacting for 5 hours, cooling and filtering, and washing with water for 3 times to obtain dry powder;
(2) dissolving the cefminox sodium crude product in a mixed solvent with the volume ratio of dichloromethane to ethanol to water being 2:1:0.3, wherein the mass of the mixed solvent is 5 times that of the mixture, adding the dry powder prepared in the step (1) with the mass of the cefminox sodium being 3 times that of the mixture, fully adsorbing the mixture, and distilling the solvent under reduced pressure to obtain load dry powder;
(3) taking macroporous resin BS-30 with the mass 30 times that of the loaded dry powder prepared in the step (2), dispersing the macroporous resin BS-30 in water, sequentially adding sucrose stearate with the mass 2% of that of the resin and KH-792 coupling agent with the mass 0.5% of that of the resin, adjusting the system to be acidic, reacting for 2 hours, washing for 5 times with water, and then filling into a column to obtain a chromatographic column;
(4) placing the loaded dry powder prepared in the step (2) on the upper layer of a chromatographic column, firstly taking an ethanol water solution with the volume ratio of 50% as a mobile phase, and discarding a chromatographic solution until cefminox sodium begins to be chromatographed; then replacing 10% ethanol water solution in volume ratio as a mobile phase, and collecting the chromatographic solution until the cefminox sodium is completely chromatographed; and (4) freezing and drying the collected chromatographic solution to obtain a pure cefminox sodium product.
The reduced pressure distillation process in the step (2) comprises the following steps: the temperature is 35 ℃, and the vacuum degree is-0.095 MPa.
Example 2
A cefminox sodium powder injection is prepared by the following purification processes:
(1) dispersing a certain amount of hydroxypropyl distarch phosphate in water with the mass multiple of 4, then sequentially adding tributyl phosphate and histidine with the mass being 1% of that of the hydroxypropyl distarch phosphate, emulsifying and dispersing, then adding epoxy chloropropane with the mass being 1.8% of that of the hydroxypropyl distarch phosphate, uniformly dispersing, adjusting the system to be alkaline, heating to 55 ℃, reacting for 4 hours, cooling and filtering, and washing with water for 4 times to obtain dry powder;
(2) dissolving the cefminox sodium crude product in a mixed solvent with the volume ratio of dichloromethane to ethanol to water being 2.5:1:0.4, adding the dry powder prepared in the step (1) with the mass ratio of cefminox sodium being 2.6 times, fully adsorbing, and distilling the solvent under reduced pressure to obtain load dry powder;
(3) taking macroporous resin BS-30 with the mass of 25 times that of the dry powder prepared in the step (2), dispersing the macroporous resin BS-30 in water, sequentially adding sucrose stearate with the mass of 1.2% of that of the resin and KH-792 coupling agent with the mass of 0.4% of that of the resin, adjusting the system to be acidic, reacting for 2 hours, washing for 4 times with water, and then loading on a column to obtain a chromatographic column;
(4) placing the loaded dry powder prepared in the step (2) on the upper layer of a chromatographic column, firstly taking an ethanol water solution with the volume ratio of 45% as a mobile phase, and discarding a chromatographic solution until cefminox sodium begins to be chromatographed; then replacing 6% ethanol water solution in volume ratio as a mobile phase, and collecting the chromatographic solution until the cefminox sodium is completely chromatographed; and (4) freezing and drying the collected chromatographic solution to obtain a pure cefminox sodium product.
The reduced pressure distillation process in the step (2) comprises the following steps: the temperature is 38 ℃, and the vacuum degree is-0.095 MPa.
Example 3
A cefminox sodium powder injection is prepared by the following purification processes:
(1) dispersing a certain amount of hydroxypropyl distarch phosphate in water with the mass multiple of 5, then sequentially adding tributyl phosphate and histidine with the mass being 1% and the mass being 8% of that of the hydroxypropyl distarch phosphate, emulsifying and dispersing, then adding epoxy chloropropane with the mass being 2% of that of the hydroxypropyl distarch phosphate, uniformly dispersing, adjusting the system to be alkaline, heating to 55 ℃, reacting for 3 hours, cooling and filtering, and washing for 5 times with water to obtain dry powder;
(2) dissolving the cefminox sodium crude product in a mixed solvent with the volume ratio of dichloromethane to ethanol to water being 3:1:0.5, adding the dry powder prepared in the step (1) with the mass ratio of cefminox sodium being 2 times, fully adsorbing, and distilling the solvent under reduced pressure to obtain a loaded dry powder;
(3) taking macroporous resin BS-30 which is 20 times of the mass of the loaded dry powder prepared in the step (2), dispersing the macroporous resin BS-30 in water, sequentially adding sucrose stearate 1% of the mass of the resin and KH-792 coupling agent 0.3%, adjusting the system to be acidic, reacting for 1h, washing for 3 times with water, and then loading on a column to obtain a chromatographic column;
(4) placing the loaded dry powder prepared in the step (2) on the upper layer of a chromatographic column, firstly taking 40% ethanol water solution in volume ratio as a mobile phase, and discarding chromatographic liquid until cefminox sodium begins to be chromatographed; then, replacing an ethanol water solution with the volume ratio of 5% as a mobile phase, and collecting a chromatographic solution until the cefminox sodium is completely chromatographed; and (4) freezing and drying the collected chromatographic solution to obtain a pure cefminox sodium product.
The reduced pressure distillation process in the step (2) comprises the following steps: the temperature is 40 ℃, and the vacuum degree is-0.09 MPa.
Example 4
A cefminox sodium powder injection is prepared by the following purification processes:
(1) dispersing a certain amount of hydroxypropyl distarch phosphate into water with the mass multiple of 2.5 times, then sequentially adding tributyl phosphate and histidine with the mass of 0.8 percent and the mass of 5 percent of the hydroxypropyl distarch phosphate, emulsifying and dispersing, then adding epoxy chloropropane with the mass of 0.6 percent of the hydroxypropyl distarch phosphate, uniformly dispersing, adjusting the system to be alkaline, heating to 48 ℃, reacting for 5.5 hours, cooling, filtering, and washing with water for 2 times to obtain dry powder;
(2) dissolving the cefminox sodium crude product in a mixed solvent with the volume ratio of dichloromethane to ethanol to water being 2.5 times of the mass of the cefminox sodium being 4:1:0.2, adding the dry powder prepared in the step (1) with the mass of the cefminox sodium being 1.5 times of the mass of the cefminox sodium, fully adsorbing, and distilling the solvent under reduced pressure to prepare load dry powder;
(3) taking macroporous resin BS-30 with the mass of 18 times that of the dry powder prepared in the step (2), dispersing the macroporous resin BS-30 in water, sequentially adding sucrose stearate with the mass of 0.8% of that of the resin and KH-792 coupling agent with the mass of 0.2%, adjusting the system to be acidic, reacting for 0.6h, washing for 2 times with water, and then filling into a column to obtain a chromatographic column;
(4) placing the loaded dry powder prepared in the step (2) on the upper layer of a chromatographic column, firstly taking 55% ethanol water solution in volume ratio as a mobile phase, and discarding chromatographic liquid until cefminox sodium begins to be chromatographed; then, replacing an ethanol water solution with the volume ratio of 15% as a mobile phase, and collecting a chromatographic solution until the cefminox sodium is completely chromatographed; and (4) freezing and drying the collected chromatographic solution to obtain a pure cefminox sodium product.
The reduced pressure distillation process in the step (2) comprises the following steps: the temperature is 32 ℃, and the vacuum degree is-0.095 MPa.
Example 5
A cefminox sodium powder injection is prepared by the following purification processes:
(1) dispersing a certain amount of hydroxypropyl distarch phosphate in water with the mass multiple of 6, then sequentially adding tributyl phosphate and histidine with the mass of 1.5% of that of the hydroxypropyl distarch phosphate, emulsifying and dispersing, then adding epoxy chloropropane with the mass of 2.5% of that of the hydroxypropyl distarch phosphate, uniformly dispersing, adjusting the system to be alkaline, heating to 60 ℃, reacting for 2 hours, cooling and filtering, and washing with water for 6 times to obtain dry powder;
(2) dissolving the cefminox sodium crude product in a mixed solvent of 5.5 times by mass of dichloromethane, ethanol and water in a volume ratio of 1.6:1:0.7, adding the dry powder prepared in the step (1) with 3.2 times by mass of cefminox sodium after complete dissolution, and carrying out reduced pressure distillation to obtain a loaded dry powder;
(3) taking macroporous resin BS-30 which is 35 times of the mass of the loaded dry powder prepared in the step (2), dispersing the macroporous resin BS-30 in water, sequentially adding sucrose stearate 2.5% of the mass of the resin and KH-792 coupling agent 0.8%, adjusting the system to be acidic, reacting for 2.5h, washing for 6 times with water, and then filling into a column to obtain a chromatographic column;
(4) placing the loaded dry powder prepared in the step (2) on the upper layer of a chromatographic column, firstly taking 35% ethanol water solution in volume ratio as a mobile phase, discarding chromatographic liquid until cefminox sodium begins to be chromatographed; then replacing an ethanol water solution with the volume ratio of 4% as a mobile phase, and collecting a chromatographic solution until the cefminox sodium is completely chromatographed; and (4) freezing and drying the collected chromatographic solution to obtain a pure cefminox sodium product.
The reduced pressure distillation process in the step (2) comprises the following steps: the temperature is 42 ℃, and the vacuum degree is-0.086 MPa.
Comparative example 1
And taking the cefminox sodium crude product as a reference substance.
Comparative example 2
A cefminox sodium powder for injection is prepared through directly loading cefminox sodium solution on column, and purifying by the same chromatographic column and chromatographic process as in example 2.
Comparative example 3
A cefminox sodium powder injection, the purification process of the cefminox sodium powder injection does not have the step (1), and hydroxypropyl distarch phosphate is directly used as dry powder, and the rest is the same as the example 2.
Comparative example 4
The cefminox sodium powder injection is purified by replacing hydroxypropyl distarch phosphate with hydroxypropyl starch in the step (1), and the rest is the same as the example 2.
Comparative example 5
The process for purifying cefminox sodium powder for injection (1) is not added with tributyl phosphate, and the rest is the same as the example 2.
Comparative example 6
The process for purifying cefminox sodium powder for injection comprises the step (1) of replacing histidine with glycine in equal amount, and the rest is the same as the example 2.
Comparative example 7
A cefminox sodium powder injection is prepared by the following steps in the purification process (1): (1) dispersing a certain amount of hydroxypropyl distarch phosphate into water with the mass multiple of 2.5 times, then sequentially adding tributyl phosphate and histidine with the mass of 0.8 percent and the mass of 5 percent of the hydroxypropyl distarch phosphate, emulsifying and dispersing, then adding epoxy chloropropane with the mass of 0.6 percent of the hydroxypropyl distarch phosphate, uniformly dispersing, adjusting the system to be alkaline, heating to 48 ℃, reacting for 5.5 hours, cooling, filtering, and washing with water for 2 times to obtain dry powder; the rest is the same as example 2.
Comparative example 8
A cefminox sodium powder injection is prepared by the purification process of cefminox sodium powder injection without the step (3), and a chromatographic column is directly prepared by macroporous resin BS-30, and the rest is the same as the step 2.
Comparative example 9
The cefminox sodium powder injection is prepared by using macroporous resin X5 to replace macroporous resin BS-30 in the step (3) of the purification process, and the rest is the same as the example 2.
Comparative example 10
A cefminox sodium powder injection is prepared by using KH550 to replace KH-792 in the step (3) of the purification process of cefminox sodium powder injection, and the rest is the same as in the example 2.
Comparative example 11
A cefminox sodium powder injection is prepared by the following steps in the purification process (3): (3) taking macroporous resin BS-30 which is 35 times of the mass of the loaded dry powder prepared in the step (2), dispersing the macroporous resin BS-30 in water, sequentially adding sucrose stearate 2.5% of the mass of the resin and KH-792 coupling agent 0.8%, adjusting the system to be acidic, reacting for 2.5h, washing for 6 times with water, and then filling into a column to obtain a chromatographic column; the rest is the same as example 2.
Comparative example 12
The purification process of the cefminox sodium powder injection (4) is to collect chromatographic solution once by taking 6 percent ethanol water solution as a mobile phase, and the rest is the same as the example 2.
Detection and analysis:
1. cefminox sodium powder injection test
(1) Yield: yield = pure cefminox sodium product/crude cefminox sodium product 100%.
(2) Content determination: according to general regulation 0512 of Chinese pharmacopoeia: measuring the content of cefminox sodium powder for injection prepared in each example and comparative example by high performance liquid chromatography, using octadecylsilane chemically bonded silica as filler, measuring wavelength at 254nm, and calculating C in the sample by peak area according to external standard method16H21N7O7S3The content of (A); the standard of the Chinese pharmacopoeia is as follows: calculated as anhydrate, cefminox C content16H21N7O7S3Not less than 91.0%.
(3) Insoluble microparticles: according to the general rule 0903 of Chinese pharmacopoeia: insoluble particle assay insoluble particles of cefminox sodium powder for injection prepared in each example and comparative example: taking 3 parts of the product, each 2.0g, adding water for microparticle examination to prepare a solution containing about 30mg in each 1 mL; the standard of the Chinese pharmacopoeia is as follows: the sample contains 10 μm and more than 10 μm of microparticles no more than 6000 microparticles and contains 25 μm and more than 25 μm of microparticles no more than 600 microparticles per 1g of sample.
(4) Bacterial endotoxin: according to general rule 1143 of Chinese pharmacopoeia: the content of bacterial endotoxin in the cefminox sodium powder injection prepared by each embodiment and the comparative example is determined by a bacterial endotoxin test method; the standard of the Chinese pharmacopoeia is as follows: the amount of bacterial endotoxin in each 1mg of cefminox should be less than 0.050 EU.
2. Pain sensation comparison test:
taking 25-30g of mice, taking 1g of each cefminox sodium powder injection prepared in the embodiment and the comparative example, dissolving the cefminox sodium powder injection in 20mL of injection water, subcutaneously injecting cefminox sodium injection according to the dosage of 20mg/kg, observing whether the mice can generate writhing reaction, judging the pain in the injection process according to the probability of the mouse generating the writhing reaction during the injection and the probability of generating twitch reaction within 5min after the injection, and repeating the test for 100 times for each sample; the results are as follows:
and finally: the above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the present invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (3)
1. A cefminox sodium powder for injection is characterized in that: the purification process of the cefminox sodium powder injection comprises the following steps:
(1) dispersing a certain amount of hydroxypropyl distarch phosphate in water with the mass multiple of 3-5, then sequentially adding tributyl phosphate accounting for 1% of the mass of the hydroxypropyl distarch phosphate and histidine accounting for 6-8% of the mass of the hydroxypropyl distarch phosphate, emulsifying and dispersing, then adding epoxy chloropropane accounting for 1-2% of the mass of the hydroxypropyl distarch phosphate, uniformly dispersing, adjusting the system to be alkaline, heating to 50-55 ℃, reacting for 3-5 h, cooling and filtering, and washing for 3-5 times with water to obtain dry powder;
(2) dissolving a cefminox sodium crude product in a mixed solvent with the mass ratio of dichloromethane to ethanol to water being 2-3: 1: 0.3-0.5 being 3-5 times, adding the dry powder prepared in the step (1) with the mass ratio of cefminox sodium being 2-3 times after complete dissolution, and distilling the solvent under reduced pressure after full adsorption to prepare a loaded dry powder;
(3) taking macroporous resin BS-30 with the mass 20-30 times that of the loaded dry powder prepared in the step (2), dispersing the macroporous resin BS-30 in water, sequentially adding 1-2% of sucrose stearate and 0.3-0.5% of KH-792 coupling agent by mass of the resin, adjusting the system to be acidic, reacting for 1-2 h, washing for 3-5 times by using water, and then loading on a column to obtain a chromatographic column;
(4) placing the loaded dry powder prepared in the step (2) on the upper layer of a chromatographic column, firstly taking an ethanol water solution with the volume ratio of 40-50% as a mobile phase, and discarding a chromatographic solution until cefminox sodium begins to be chromatographed; then, replacing an ethanol water solution with the volume ratio of 5-10% as a mobile phase, and collecting a chromatographic solution until the cefminox sodium is completely chromatographed; and (4) freezing and drying the collected chromatographic solution to obtain a pure cefminox sodium product.
2. The cefminox sodium powder for injection according to claim 1, which is characterized in that: the reduced pressure distillation process in the step (2) comprises the following steps: the temperature is 35-40 ℃, and the vacuum degree is-0.09 MPa to-0.095 MPa.
3. The cefminox sodium powder for injection according to claim 1 or 2, which is characterized in that: the pure cefminox sodium product is packaged into cefminox sodium powder for injection with the specification of 0.5g or 1.0 g.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210038198.7A CN114601805A (en) | 2022-01-13 | 2022-01-13 | Cefminox sodium powder for injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210038198.7A CN114601805A (en) | 2022-01-13 | 2022-01-13 | Cefminox sodium powder for injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114601805A true CN114601805A (en) | 2022-06-10 |
Family
ID=81857419
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210038198.7A Pending CN114601805A (en) | 2022-01-13 | 2022-01-13 | Cefminox sodium powder for injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114601805A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101982469A (en) * | 2010-10-22 | 2011-03-02 | 东瑞（南通）医药科技有限公司 | Method for removing bacterial endotoxins in cephalosporin antibiotics by utilizing macroporous adsorption resins |
| CN102020666A (en) * | 2010-12-02 | 2011-04-20 | 陶灵刚 | Cefminox sodium compound and new preparation method thereof |
| CN103055832A (en) * | 2012-12-31 | 2013-04-24 | 浙江月旭材料科技有限公司 | Chromatographic packing for separating water soluble polymer and protein and preparation method of same |
| CN105924456A (en) * | 2016-06-17 | 2016-09-07 | 重庆福安药业集团庆余堂制药有限公司 | Cefminox sodium compound reducing adverse reactions and preparation thereof |
-
2022
- 2022-01-13 CN CN202210038198.7A patent/CN114601805A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101982469A (en) * | 2010-10-22 | 2011-03-02 | 东瑞（南通）医药科技有限公司 | Method for removing bacterial endotoxins in cephalosporin antibiotics by utilizing macroporous adsorption resins |
| CN102020666A (en) * | 2010-12-02 | 2011-04-20 | 陶灵刚 | Cefminox sodium compound and new preparation method thereof |
| CN103055832A (en) * | 2012-12-31 | 2013-04-24 | 浙江月旭材料科技有限公司 | Chromatographic packing for separating water soluble polymer and protein and preparation method of same |
| CN105924456A (en) * | 2016-06-17 | 2016-09-07 | 重庆福安药业集团庆余堂制药有限公司 | Cefminox sodium compound reducing adverse reactions and preparation thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104800221B (en) | Medicinal cefetamet pivoxil hydrochloride composition for treating sensitive bacteria infectious diseases | |
| CN102718843B (en) | Preparation method of single teicoplanin components | |
| CN102161666A (en) | Preparation method of mezlocillin sodium and mezlocillin sodium for injection | |
| CN101695489B (en) | Aztreonam composition, powder injection and preparation method thereof | |
| CN103417512B (en) | A kind of Biomox and preparation method thereof | |
| CN113365973B (en) | Phenoxyacetic acid derivative and method for preparing penicillin V salt by using same through enzymatic method | |
| CN114601805A (en) | Cefminox sodium powder for injection and preparation method thereof | |
| CN112442096A (en) | High-purity Zhongshengmycin F reference substance and preparation method thereof | |
| CN103232449A (en) | Aztreonam compound, as well as preparation method and pharmaceutical composition thereof | |
| CN102070539B (en) | 1-oxo-2-methyl-3-(1-ethoxyl)-quinoxaline and preparation method and application thereof | |
| CN106432276A (en) | Cefazolin sodium compound prepared according to novel intelligent crystallization technology and preparation of cefazolin sodium compound | |
| CN110498823B (en) | Synthetic method of 6' -N-ethyl gentamicin C1a | |
| CN101787039B (en) | High-purified cefmetazole sodium compound | |
| CN101152195B (en) | Application of aminoglycoside antibiotic in preparing pharmaceutical composition for treating drug-fast bacteria infection | |
| CN103232477A (en) | Cefotiam hydrochloride compound, and preparation method and pharmaceutical composition thereof | |
| CN102321100A (en) | Preparation method of cefminox sodium | |
| CN102690333B (en) | Preparation method of high-purity teicoplanin | |
| CN102070540B (en) | 1-oxygen-2-(1-ethoxy)-3-methyl-quinoxaline, and preparation method and application thereof | |
| CN108409837A (en) | One group of glycopeptide compound, preparation method and application with anti-drug resistance bacterial activity | |
| AU712904B2 (en) | Improved process for preparing potassium clavulanate | |
| CN109320527B (en) | Cervidomycin (Cervinomycin) B1, B2, B3 and B4, and production method and application thereof | |
| CN111039999A (en) | Synthesis method of etimicin impurity | |
| CN110117310A (en) | A kind of purification process of Daptomycin | |
| CN114774497B (en) | Method for preparing lipopeptide antibiotic iturin A by using capsicum stalks | |
| EP1481005A1 (en) | Dab sp 9 /sp DERIVATIVES OF LIPOPEPTIDE ANTIBIOTICS AND METHODS OF MAKING AND USING THE SAME |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |