CN105769770A - Cefotiam hydrochloride powder injection preparation for injection - Google Patents
Cefotiam hydrochloride powder injection preparation for injection Download PDFInfo
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- CN105769770A CN105769770A CN201610312663.6A CN201610312663A CN105769770A CN 105769770 A CN105769770 A CN 105769770A CN 201610312663 A CN201610312663 A CN 201610312663A CN 105769770 A CN105769770 A CN 105769770A
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- cefotiam
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- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
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- 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
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- 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
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- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
Abstract
The invention belongs to a medicinal preparation, and mainly relates to a cefotiam hydrochloride powder injection preparation for injection. The cefotiam hydrochloride powder injection preparation for injection comprises the following formula components: cefotiam hydrochloride, medicinal basic amino acid, medicinal anhydrous sodium phosphate and medicinal lidocaine hydrochloride. The cefotiam hydrochloride powder injection preparation is high in stability, flowability and solubility, low in impurity content, accurate in dosage and uniform in granularity, and false positive and side effects are avoided to a certain extent.
Description
Technical field
The invention belongs to pharmaceutical preparation, relate generally to a kind of injection cefotiam chloride powder injection formulation.
Background technology
Cefotiam, has another name called (6R-is trans)-7-[[(2-amino-4-thiazolyl) acetyl group] amino]-3-[[[1-[(2-(dimethylamino) ethyl]-1H-TETRAZOLE-5-base] sulphomethyl]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid dihydrochloride.Its structural formula is:
Cefotiam is developed by Takede Chemical Industries Ltd of Japan the earliest, and goods are dihydrochloride, and added with a certain amount of natrium carbonicum calcinatum.Its dihydrochloride conventional, for white or micro-yellow powder；Slightly special smelly；The i.e. effervescent that adds water dissolves the clear solution generating weakly acidic pH, is slightly soluble in ethanol, insoluble in acetone chloroform.
This product is second generation cephalosporin class antibiotic.Effect and cefazolin to gram positive bacteria are close, and to gram-negative bacteria, as more excellent in effects such as haemophilus, escherichia coli, klebsiella spp, proteus mirabilises, enterobacteria, citrobacter, indole-positive Bacillus proteus etc. also there are is antibacterial action.Its mechanism of action is combine with the penicillin-binding protein (PBPs) on bacterial cell membrane; make transpeptidase acidylate; suppress in antibacterial every the synthesis with cell wall; affect the cross-connection of cell wall mucopeptide composition; cell division and growth is made to be suppressed; ne ar is elongated, finally dissolves and dead.
Following infection caused by application this product treatment sensitive organism clinically: 1, postoperative infection.2, burn infection.3, skin soft-tissue infection: subcutaneous abscess, carbuncle, furuncle etc..4, bone and the infection of joint: osteomyelitis, suppurative arthritis.5, respiratory system infection: tonsillitis (peritonsillitis, peritonsillar abscess), bronchitis, bronchus exaggeration concurrent infection, pneumonia, pulmonary suppuration disease, empyema etc..6, biliary tract infection: cholangitis, cholecystitis etc..7, urogenital infections: pyelonephritis, cystitis, urethritis, prostatitis, endometritis, pelvic inflammatory disease, parametritis, adnexitis, bartholinitis etc..8, ear, nose, larynx infect: otitis media, nasal sinusitis, sinusitis.9, other: septicemia, meningitis, peritonitis etc..
At present, the preparation that cefotiam uses clinically is cefotiam chloride powder preparation mixed with sodium carbonate.Owing to adding substantial amounts of natrium carbonicum calcinatum in preparation, therefore, this mixed powder preparation is producing and there is many unfavorable factors in clinical practice:
1), need to carry out evacuation after the mixed powder subpackage of cefotiam, cause generation technique loaded down with trivial details.
2), owing to adding substantial amounts of natrium carbonicum calcinatum in preparation, strong basicity environment, easily caused by the generation of cefotiam impurity, causes false positive or side reaction further.
3), medicine is when dissolving, and hydrochloric acid and sodium carbonate react, and can produce substantial amounts of carbon dioxide, causing pressure in bottle excessive, it is possible to cause medicinal liquid to pass in and out, syringe piston even can be ejected by pressure of the inside of a bottle, severe patient causes bottle explosion, thus wasting medicine, lessens the curative effect.Even medical personnel are produced the potentially danger of personal injury.
4), when to intravenous drip, the carbon dioxide bubble of generation not easily drains, and clarity is observed and causes difficulty.
5), natrium carbonicum calcinatum, alkalescence is strong, makes preparation stability reduce, a large amount of injections easily generation alkalosis disease.
6), due to the existence of sodium ion, there is certain local irritation, reduce compliance and the curative effect of patient.
7), substantial amounts of sodium ion, limit clinical application range, the heart, renal insufficiency person, edematous patient, neonate, anemia of pregnant woman and old people's use can be increased the weight of physiological load, increase untoward reaction, affect the treatment.
Summary of the invention
In view of this, pharmaceutical preparation (injectable powder) that it is an object of the invention to provide a kind of compositions containing cefotiam chloride and preparation method thereof.Its quality of the pharmaceutical preparations stablize controlled, untoward reaction is little and simple process.
For realizing the purpose of the present invention, the present invention adopts the following technical scheme that
A kind of injection cefotiam chloride powder injection formulation, its prescription consists of: cefotiam chloride, acceptable basic aminoacid, medicinal anhydrous sodium phosphate and medicinal hydrochloric acid lignocaine.
Acceptable basic aminoacid be arginine, lysine, histidine any one, it is preferable that medicinal arginine.
It is 70～120 μm that described cefotiam chloride aseptic powder and the particle diameter of pharmaceutic adjuvant are, it is preferable that 80～110 μm.Wherein medicinal anhydrous sodium phosphate and the amino acid whose effect of acceptable basic are the pH value regulating preparation, so as to meet country's requirement about preparation pH value range, increase the dissolubility of cefotiam simultaneously.Keenly feel when the effect of medicinal hydrochloric acid lignocaine is to alleviate injection, improve compliance and the curative effect of patient.
It is 1:0.05-0.10:0.01-0.02:0.01-0.02 that described cefotiam chloride (counts) weight ratio with medicinal anhydrous sodium phosphate, acceptable basic aminoacid and medicinal hydrochloric acid lignocaine with cefotiam, it is preferable that 1:0.1:0.01:0.01.In order to confirm the ratio of each component in this preparation, We conducted correlation test, Main Basis is the national standard of this product, and its pH value range should be 5.7-7.2, and we have attempted multiple prescription, as shown in table 1:
Table 1 cefotiam chloride preparation prescription proportioning
According to above prescription, we have detected solution color, clarity and pH value, and result is as shown in table 2:
Table 2 cefotiam chloride prescription solution color, clarity and pH value testing result
According to the above results, we have found that, when the weight ratio of cefotiam chloride (in cefotiam) and medicinal anhydrous sodium phosphate, acceptable basic aminoacid and medicinal hydrochloric acid lignocaine is within the scope of 1:0.10:0.01-0.02:0.01-0.02, its pH value drops in critical field, and when weight ratio is 1:0.1:0.01:0.01, pH value is ideal value 6.50.
Pharmaceutical preparation preparation method of the present invention is: cefotiam chloride aseptic powder and pharmaceutic adjuvant being crossed 100 mesh sieves and carries out precrushing, recycling jet mill carries out in small, broken bits, mixes 2h after obtaining material.
Every bottle preferably containing main composition cefotiam chloride 1g, medicinal anhydrous sodium phosphate 100mg, acceptable basic amino acid/11 0mg, medicinal hydrochloric acid lignocaine 10mg.
The preparation method of pharmaceutical preparation of the present invention and medicine bottle is: aluminium-plastic cap is removed through outer package, dries 180 minutes, cool down standby in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, is carried out by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools down standby.Vial is removed through outer package, is cleaned by cleaning machine and clean compressed air dries up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool down standby.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, sets the mixed powder time as 3h, standby.Cefotiam chloride aseptic powder in small, broken bits to 100 mesh sieves excessively and jet mill and pharmaceutic adjuvant are poured in batch mixer successively, cover lid, start motor, mixed powder 3h, open Cap for tin body and baiting valve carries out blowing.According to dosage carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.Undertaken rolling lid by sample intact to subpackage tamponade.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Disclosure one cefotiam chloride composition powder injection and preparation method thereof, prescription effective ingredient is formed by as the cefotiam chloride of active component, acceptable basic aminoacid, medicinal anhydrous sodium phosphate and medicinal hydrochloric acid lignocaine, and the weight ratio of cefotiam chloride (counting with cefotiam) and medicinal anhydrous sodium phosphate, acceptable basic aminoacid and medicinal hydrochloric acid lignocaine is 1:0.05-0.10:0.01-0.02:0.01-0.02.Preparation method is by cefotiam chloride aseptic powder and pharmaceutic adjuvant mix homogeneously, directly mixed-powder is sub-packed in the control antibiotic glass bottle after sterilization, jump a queue immediately and seal with aluminium-plastic cap, obtaining injection cefotiam chloride composition powder injection.
Can be seen that from above-mentioned technical scheme, there is following remarkable advantage in the present invention: 1, the cefotiam chloride composition powder injection good stability of the present invention, impurity content are few, avoid the generation of false positive and side effect to a certain extent, additionally said preparation good fluidity, dosage is accurate, granule is uniform, dissolubility is high.2 and conventional sodium carbonate directly alkalize and be slightly different, medicinal sodium phosphate presented strong basicity reaction later by being hydrolyzed in water, has the effects such as complexation, buffering, pH adjusting agent as pharmaceutic adjuvant, can be used for the preparation of eye drop, injection.Replace sodium carbonate with sodium phosphate and basic amino acid, decrease the consumption of sodium ion, to the heart, renal insufficiency person, neonate, anemia of pregnant woman and be suitable for per capita old age, expand use scope, also avoid alkalotic probability.3, when medicine dissolves, carbon dioxide will not be produced, the observation of clarity when so both infuse without influence on intravenous drip, more avoid the danger of bottle explosion.4, evacuation need not be carried out after product subpackage, decrease operation.5, cefotiam chloride compositions powder ampoule agent for injection provided by the invention alleviates pain during injection, and compared with positive drug control group, significantly improves compliance and the curative effect of patient.6, the preparation method of injection cefotiam chloride composition powder injection of the present invention is sterile raw material and pharmaceutic adjuvant directly accurate mixed powder, subpackage, simple in production process operation, technology maturation, it is easy to control, equipment and preparation condition is less demanding, cost is low, is suitable to large-scale production.
Detailed description of the invention
The invention will be further described by way of example more below, provides the implementation detail of the present invention, but is not intended to limit protection scope of the present invention.
Embodiment 1
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool down standby in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, is carried out by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools down standby.Vial is removed through outer package, is cleaned by cleaning machine and clean compressed air dries up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool down standby.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, sets the mixed powder time as 3h, standby.By cross 100 mesh sieves and jet mill in small, broken bits cefotiam chloride 5000g, medicinal anhydrous sodium phosphate 500g, acceptable basic aminoacid 50g and medicinal hydrochloric acid lignocaine 50g pour in batch mixer successively, cover lid, start motor, mixed powder 3h, open Cap for tin body and baiting valve carries out blowing.By every 1 bottle containing the standard of main composition cefotiam chloride 1g, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.Undertaken rolling lid by sample intact to subpackage tamponade.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 2
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool down standby in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, is carried out by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools down standby.Vial is removed through outer package, is cleaned by cleaning machine and clean compressed air dries up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool down standby.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, sets the mixed powder time as 3h, standby.By cross 100 mesh sieves and jet mill in small, broken bits cefotiam chloride 5000g, medicinal anhydrous sodium phosphate 500g, acceptable basic aminoacid 50g and medicinal hydrochloric acid lignocaine 50g pour in batch mixer successively, cover lid, start motor, mixed powder 3h, open Cap for tin body and baiting valve carries out blowing.By every 1 bottle containing the standard of main composition cefotiam chloride 0.5g, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.Undertaken rolling lid by sample intact to subpackage tamponade.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 3
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool down standby in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, is carried out by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools down standby.Vial is removed through outer package, is cleaned by cleaning machine and clean compressed air dries up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool down standby.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, sets the mixed powder time as 3h, standby.By cross 100 mesh sieves and jet mill in small, broken bits cefotiam chloride 5000g, medicinal anhydrous sodium phosphate 500g, acceptable basic aminoacid 50g and medicinal hydrochloric acid lignocaine 50g pour in batch mixer successively, cover lid, start motor, mixed powder 3h, open Cap for tin body and baiting valve carries out blowing.By every 1 bottle containing the standard of main composition cefotiam chloride 1g, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.Undertaken rolling lid by sample intact to subpackage tamponade.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 4
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool down standby in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, is carried out by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools down standby.Vial is removed through outer package, is cleaned by cleaning machine and clean compressed air dries up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool down standby.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, sets the mixed powder time as 3h, standby.By cross 100 mesh sieves and jet mill in small, broken bits cefotiam chloride 5000g, medicinal anhydrous sodium phosphate 500g, acceptable basic aminoacid 50g and medicinal hydrochloric acid lignocaine 50g pour in batch mixer successively, cover lid, start motor, mixed powder 3h, open Cap for tin body and baiting valve carries out blowing.By every 1 bottle containing the standard of main composition cefotiam chloride 1g, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.Undertaken rolling lid by sample intact to subpackage tamponade.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 5
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool down standby in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, is carried out by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools down standby.Vial is removed through outer package, is cleaned by cleaning machine and clean compressed air dries up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool down standby.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, sets the mixed powder time as 3h, standby.By cross 100 mesh sieves and jet mill in small, broken bits cefotiam chloride 5000g, medicinal anhydrous sodium phosphate 500g, acceptable basic aminoacid 50g and medicinal hydrochloric acid lignocaine 50g pour in batch mixer successively, cover lid, start motor, mixed powder 3h, open Cap for tin body and baiting valve carries out blowing.By every 1 bottle containing the standard of main composition cefotiam chloride 1g, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.Undertaken rolling lid by sample intact to subpackage tamponade.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 6
Prescription: cefotiam chloride 5000g (in cefotiam)
Medicinal sodium carbonate 1250g
Make 5000
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool down standby in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, is carried out by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools down standby.Vial is removed through outer package, is cleaned by cleaning machine and clean compressed air dries up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool down standby.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, sets the mixed powder time as 3h, standby.By cross 100 mesh sieves and jet mill in small, broken bits cefotiam chloride 5000g, medicinal sodium carbonate 1250g, pour in batch mixer successively, cover lid, start motor, mixed powder 3h, open Cap for tin body and baiting valve carries out blowing.By every 1 bottle containing the standard of main composition cefotiam chloride 1g, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.Undertaken rolling lid by sample intact to subpackage tamponade.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 7
Producing three batches of injection cefotiam chloride powder injection formulations respectively continuously according to the method for embodiment 1-6, products obtained therefrom carries out particle diameter, content, purity, pH value and water solublity and measures, measurement result is in Table 1.
The different particle diameter of cefotiam chloride injectable powder of table 3, content, purity, pH value and water solublity measurement result
From table 3 result, cefotiam chloride powder injection formulation dosage of the present invention is accurately, good stability, impurity content are few, granule is uniform, dissolubility is high.
Embodiment 8
Detecting above group is first the dissolution velocity of cefotiam chloride injectable powder of embodiment 1-6, and does control experiment with the cefotiam chloride preparation of listing.
Table 4 dissolution velocity comparative experiments result
| Numbering | Dissolution velocity |
| Embodiment 1 first | 10s |
| Embodiment 2 first | 10s |
| Embodiment 3 first | 17s |
| Embodiment 4 first | 23s |
| Embodiment 5 first | 20s |
| Embodiment 6 first | 19s |
| Listing cefotiam chloride preparation | 25s |
From table 4 result, cefotiam chloride powder injection formulation dissolution velocity of the present invention significantly improves.
Embodiment 9
By the operation standard of long-term experiment and Acceleration study, detecting above group is first the stability of cefotiam chloride injectable powder of embodiment 1-6, and does control experiment with the cefotiam chloride preparation of listing.Wherein cefotiam chloride and related impurities content adopt high performance liquid chromatography (HPLC) detection.Concrete testing conditions is as follows:
Pillar: CAPCELLPAKACR-C18 liquid-phase chromatographic column, internal diameter 4.6mm, length 25cm, particle diameter 5 μm.Column temperature: 35 DEG C.Detection wavelength: 254nm.Flow velocity: 1ml/min.Mobile phase: phosphate buffer (disodium hydrogen phosphate of use 0.05mol/L and the potassium dihydrogen phosphate preparation of 0.05mol/L, and pH is adjusted to 7.6-7.8 (volume ratio is about 4:1)) as eluent A, acetonitrile is as eluent B.
Long-term stable experiment condition: be placed in climatic chamber by sample, keeps temperature 25 DEG C ± 2；Humidity 60% ± 5, regular pick test, experimental result is as shown in the table:
The long-term experiment result of the different cefotiam chloride injectable powder of table 5
Table 6 lists the long-term experiment result of cefotiam chloride preparation
Accelerated stability test condition: be placed in climatic chamber by sample, keeps temperature 40 DEG C ± 2；Humidity 75% ± 5, regular pick test, experimental result is as shown in the table:
The Acceleration study result of the different cefotiam chloride injectable powder of table 7
Table 8 lists the Acceleration study result of cefotiam chloride preparation
Cefotiam chloride injectable powder and long-term experiment and the Acceleration study result of listing cefotiam chloride preparation according to the above present invention show, cefotiam chloride injectable powder provided by the invention has higher purity and better stability than the cefotiam chloride preparation of listing, and the cefotiam chloride injectable powder quality safety of the present invention is stable in storage process, it is possible to long term storage.
Embodiment 9
This product is aseptic subpackaged goods, injection after needing the injection solvent being suitable for dissolve in Clinical practice process.For investigating this product stability in use, this product has been carried out compatibility stability research by us, and contrasts with listing sample.
The sample of Example 1 and commercially available product add in 0.9% sodium chloride solution and 5% glucose injection respectively, shake up；Placing 4 hours at 5 DEG C, 25 DEG C, 40 DEG C, observe solution appearance, calculate the cefotiam relative amount of each time point respectively and investigate its change having related substance, result of the test is as follows:
Table 9 and 0.9% sodium chloride injection compatibility stability investigate result
Table 10 and 5% glucose injection compatibility stability investigate result
As can be seen here, according to injection cefotiam chloride prepared by the present invention, its stability in 0.9% sodium chloride injection and 5% glucose injection is slightly better than commercialized product.
Embodiment 10
The protective effect of mice attacked by the injection cefotiam chloride preparation of this experimentation embodiment of the present invention 1 preparation and commercially available cefotiam chloride preparation reply gram negative bacteria (for escherichia coli); carrying out drug administration by injection mode, specific experiment method is as follows:
Mice 100, body weight is about 20g, male and female half and half, is divided into 4 groups by injection system at random, and often group 25, is divided into matched group, escherichia coli group, cefotiam group of the present invention (10mg/kg) and commercially available cefotiam group (10mg/kg).Wherein matched group gives normal saline, and escherichia coli group gives 10-6The viable bacteria normal saline of cfu/kg, cefotiam group of the present invention and commercially available cefotiam group give 10 after giving cefotiam normal saline respectively again-6The escherichia coli of cfu/kg.
Drug administration by injection is, during mice is normally fed, choose caudal vein, with 75% cotton ball soaked in alcohol wiping, fixing tail, is directed at blood vessel central authorities at tail end 1/3 place with 30.Angle inserting needle, then syringe needle is lifted, the angle parallel with afterbody is thrust, and parallel propelling is a little, injects complete, takes cotton balls pressing soft, observes the situation of 7 days mices.
Table 11 cefotiam is to experimental data (injection) in the Mice Body of escherichia coli
Above-mentioned test result indicate that the mice of infection due to Escherichia coli is all served protective effect by cefotiam of the present invention and commercially available cefotiam preparation, it is possible to reduce the mortality rate of mice.But cefotiam preparation of the present invention not only has antibacterial action, and is safe on using.
Embodiment 11
The cefotiam chloride compositions powder ampoule agent for injection that embodiment of the present invention 1-5 provides is weak to the effect of blood circulation, to autonomic nervous system without any effect.To mice urine volume and sodium, potassium excretion, on mice intestinal tube transhipment energy, gastric secretion without impact.
After the explanation having read this method, the present invention can be made various change or amendment by those skilled in the art, and these equivalent form of values fall within the limited scope of the application appended claims equally.
Claims (7)
1. the composition powder injection containing cefotiam chloride, it is characterised in that: prescription effective ingredient is formed by as the cefotiam chloride of active component, acceptable basic aminoacid, medicinal anhydrous sodium phosphate and medicinal hydrochloric acid lignocaine；Wherein acceptable basic aminoacid be arginine, lysine, histidine any one；It is 70～120 μm that described cefotiam chloride aseptic powder and the particle diameter of pharmaceutic adjuvant are.
2. pharmaceutical preparation according to claim 1, it is characterised in that: described acceptable basic aminoacid is arginine.
3. pharmaceutical preparation according to claim 1, it is characterised in that: it is 1:0.05-0.10:0.01-0.02:0.01-0.02 that cefotiam chloride (counts) weight ratio with medicinal anhydrous sodium phosphate, acceptable basic aminoacid and medicinal hydrochloric acid lignocaine with cefotiam.
4. pharmaceutical preparation according to claim 3, it is characterised in that: it is 80～110 μm that described cefotiam chloride aseptic powder and the particle diameter of pharmaceutic adjuvant are.It is 1:0.1:0.01:0.01 that described cefotiam chloride (counts) weight ratio with medicinal anhydrous sodium phosphate, acceptable basic aminoacid and medicinal hydrochloric acid lignocaine with cefotiam.
5. the preparation method of the arbitrary described pharmaceutical preparation of claim 1 is: cefotiam chloride aseptic powder and pharmaceutic adjuvant being crossed 100 mesh sieves and carries out precrushing, recycling jet mill carries out in small, broken bits, mixes 2h after obtaining material.
6. the medicine bottle of pharmaceutical preparation according to claim 4, it is characterised in that: every bottle containing main composition cefotiam chloride 1g, medicinal anhydrous sodium phosphate 100mg, acceptable basic amino acid/11 0mg, medicinal hydrochloric acid lignocaine 10mg.
7. the preparation method of the medicine bottle of pharmaceutical preparation described in claim 1, it is characterised in that comprise the steps:
1) cleaning preparation vessels and batch mixer, including:
Plastic-aluminum is placed in 120 DEG C of baking ovens and dries 180 minutes, cool down standby；
Rubber cork is carried out by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools down standby；
Vial is cleaned by cleaning machine and clean compressed air dries up, and eventually passes 350 DEG C of dry heat sterilizations 10 minutes, cools down standby；
Cleaning batch mixer tank body and baiting valve, regulate intervalometer, sets the mixed powder time as 3h, standby.
2) cefotiam chloride aseptic powder in small, broken bits to 100 mesh sieves excessively and jet mill and pharmaceutic adjuvant are poured in batch mixer successively, mixed powder 3h；
3) aseptic subpackaged, including:
Mixed powder opens Cap for tin body after completing and baiting valve carries out blowing, according to dosage carries out aseptic subpackaged with control antibiotic glass bottle, tamponade；Undertaken rolling lid by sample intact to subpackage tamponade.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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