CN103142615A - Ceftriaxone sodium pharmaceutical composition and preparation method thereof - Google Patents
Ceftriaxone sodium pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN103142615A CN103142615A CN2013100750018A CN201310075001A CN103142615A CN 103142615 A CN103142615 A CN 103142615A CN 2013100750018 A CN2013100750018 A CN 2013100750018A CN 201310075001 A CN201310075001 A CN 201310075001A CN 103142615 A CN103142615 A CN 103142615A
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- metronidazole
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- lipid microsphere
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Abstract
The invention provides a ceftriaxone sodium pharmaceutical composition and a preparation method thereof, relating to the field of a medicinal preparation and a preparation method thereof. The invention mainly solves the problems of high dosage of single ceftriaxone sodium and metronidazole preparation, poor treatment effect after combination, and great side effect in the prior art. The pharmaceutical composition comprises ceftriaxone sodium and metronidazole lipid microspheres in a weight ratio of 100:3-100:10, wherein the weight of the metronidazole lipid microspheres is metered on the basis of metronidazole; and when the pharmaceutical composition is prepared into a powder injection, the pH value of the water solution of the pharmaceutical composition is 6.5-7.0. The pharmaceutical composition powder injection provided by the invention has high curative effect, and can reduce the consumption of the metronidazole by more than 80%, thereby greatly relieving or avoiding the toxic and side effects of the metronidazole, especially digestive tract reactions, including nausea, vomit, inappetence, abdominal colic and neurotoxicity, and lowering the incidence rate of adverse reactions.
Description
Technical field:
The present invention relates to pharmaceutical preparation and preparation method field, relate in particular to a kind of ceftriaxone sodium pharmaceutical composition and preparation method thereof.
Background technology:
The ceftriaxone sodium chemical name is: [6R-[6alpha; 7beta (Z)]]-3-[[(1; 2; 5; 6-tetrahydrochysene-2-methyl-5; 6-dioxo-1,2,4-triazine-3-yl) sulfur] methyl]-7-[[(2-amino-4-thiazolyl] (methoxyimino) acetyl group] amino]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid sodium salt.Molecular formula: C
18H
16N
8Na
2O
7S
33H
2O, molecular weight: 661.59.Its chemical structural formula is:
Ceftriaxone sodium is the Third generation Cephalosporins antibiotic, be used for lower respiratory infection, urinary tract, biliary tract infection due to responsive pathogenic bacterium, and abdominal cavity infection, pelvic infection, skin soft-tissue infection, bone and the infection of joint, septicemia, meningitis etc. and average of operation periods infection mitigation.
1972, Tally found that first metronidazole has the effect of whole body anaerobe resistant, and was defined as the drug of first choice of anti anaerobic bacteria infection by World Health Organization (WHO) in 1978.In clinical extensive use, its purposes is widened day by day along with metronidazole, and its advantage is: the scope of anaerobe resistant is wide, and sterilizing power is strong, general avirulence, and side reaction is few, has no drug resistance.It has tablet, injection, suppository, compound preparation, can be for oral, quiet notes and anus plug, also can be applied to intravenously administrable with other multiple antibacterials preparation, so, the requisite a kind of curative of clinical departments become.Recently studying its mechanism of action is, answers by its reduzate and bacterial cell DNA antisense, disturbs growth, the breeding of antibacterial, last kill bacteria.
infection in clinical operation usually is accompanied by the mixed infection that contains anaerobe and aerobe, rather than the infection of single anaerobe or aerobe, it is the clinical first-selected medication for the treatment of anaerobic infection because of metronidazole, ceftriaxone sodium commonly used and metronidazole drug combination contain the MOI of anaerobe for preventing post-operation infection and treatment clinically, but ceftriaxone for inj and injection metronidazole are all single product preparations, during the difference medication, the consumption of metronidazole is very large, the toxic and side effects of metronidazole is very strong, the metronidazole of normal therapeutic dosage can produce digestive tract reaction, the most common comprise nauseating, vomiting, inappetence, abdominal colic and higher neurotoxicity.To this for clinical provide a kind of safe and effective, medicine that toxic and side effects is low is extremely urgent, Given this, proposes the present invention.
Summary of the invention:
Technical problem to be solved by this invention is to overcome the defective of prior art, provide a kind of curative effect high, safe, good stability, the ceftriaxone sodium pharmaceutical composition that toxic and side effects is low, this pharmaceutical composition principal agent is: ceftriaxone sodium and metronidazole lipid microsphere, said composition can effectively be treated the MOI that contains anaerobe.
Technical problem to be solved by this invention realizes by the following technical solutions.
A kind of ceftriaxone sodium pharmaceutical composition, it is characterized in that, this pharmaceutical composition comprises ceftriaxone sodium and metronidazole lipid microsphere, the weight ratio of ceftriaxone sodium and metronidazole lipid microsphere is 100:3-100:10, the weight of metronidazole lipid microsphere is in metronidazole, this pharmaceutical composition is prepared into powder ampoule agent for injection, and the pH value of the aqueous solution of this pharmaceutical composition is 6.5-7.0.
In this pharmaceutical composition, the preferred weight ratio of ceftriaxone sodium and metronidazole lipid microsphere is 100:5, and the weight of metronidazole lipid microsphere is in metronidazole, and the preferred pH value of the aqueous solution of this pharmaceutical composition is 6.5-6.8.
Another object of the present invention is to provide a kind of method that ceftriaxone sodium pharmaceutical composition is prepared into powder ampoule agent for injection, it is characterized in that, the concrete steps of the method are:
(1) preparation metronidazole lipid microsphere, this goods mean diameter is less than 120 nm, and pH value is between 6.5-6.8, and the absolute value of Zeta-potential is greater than 20 mV, and envelop rate is more than 80%.
The crude drug component of preparation metronidazole lipid microsphere is:
The step of preparation metronidazole lipid microsphere is:
A) glycerol for injection and the poloxamer F-68 with recipe quantity is dissolved in water for injection, be placed in 80 ℃ of water bath with thermostatic control magnetic stirring apparatuss and be stirred to whole dissolvings, make mixture A, the injection water yield can be with abundant fused the getting final product of glycerol for injection and poloxamer F-68;
B) recipe quantity oleic acid is added in the oil phase that is consisted of by long-chain fat acid glyceride and medium chain length fatty acid triglyceride, forms and mix oil phase;
C) fabaceous lecithin and the metronidazole with recipe quantity adds in dehydrated alcohol 200ml, is stirred to fabaceous lecithin and metronidazole under 80 ℃ all after dissolving, and decompression volatilizes dehydrated alcohol, then adds the mixing oil phase, stirs and makes mixture B;
D) mixture A is added in mixture B, be placed in the 8000r/min of high-speed tissue mashing machine and stir 3 times, each 3min;
E) regulate pH value to 6.5-6.8, water for injection is settled to 1000ml, adds in high pressure homogenizer 70MPa homogenizing 8 times;
F) bottling, gland, 100 ℃ of sterilization 30min, the rapid cooling of ice-water bath and get final product, standby;
(2) with the metronidazole lipid microsphere of recipe quantity, directly be added in the water for injection of recipe quantity, the injection water yield can be dissolved the metronidazole lipid microsphere fully and be got final product;
(3) after stirring and dissolving the pH value of regulator solution in the 6.5-6.8 scope;
(4) and then by 0.45 μ m, 0.22 μ m filter membrane carry out the degerming circulating filtration, 30 minutes time;
(5) after pick test meets the requirements, solution is divided be filled in the rustless steel pallet, enter freeze drying box, carry out lyophilization and process, obtain the aseptic freeze-dried powder of metronidazole lipid microsphere, pulverize and sieve;
(6) metronidazole lipid microsphere lyophilized powder and the ceftriaxone sodium sterilized powder after pulverizing and sieving is mixed in proportion, and after pick test meets the requirements, carries out packing according to labelled amount, namely gets required powder ampoule agent for injection.
The specification that described ceftriaxone sodium pharmaceutical composition is prepared into powder ampoule agent for injection is 0.5g/ bottle and 1.0g/ bottle, and quality is in ceftriaxone.
Pharmaceutical composition preparation technology of the present invention is simple, has guaranteed well the growth of related substance in the storage of the stability of active component and finished product.
The present invention is directed to treatment clinically and contain the MOI of anaerobe and propose, a kind of ceftriaxone for inj composition powder injection is provided.The every consumption per day of ceftriaxone sodium list product preparation adult is 2.0 left and right clinically, and the consumption that metronidazole list product preparation is grown up every day is the 2g left and right.in ceftriaxone sodium pharmaceutical composition provided by the invention, ceftriaxone sodium, metronidazole lipid microsphere (take metronidazole) weight ratio (W/W) is 100:3-100:10, therefore the every consumption per day of ceftriaxone sodium is 2.0g, when dividing the secondary administration, the consumption of metronidazole every day is 60mg-200mg, each consumption is 30mg-100mg, be that 4000ml calculates by the normal adult total blood volume, after each administration, blood drug level is 7.5-25 μ g/ml, and the metronidazole effective blood drug concentration is 2-8 μ g/ml, the metronidazole lipid microsphere has slow releasing function, the effective blood drug concentration time can keep more than 12 hours in vivo.Pharmaceutical composition powder pin provided by the invention not only has high curative effect thus, and can reduce metronidazole consumption (using more than 80% less), thereby greatly alleviate or avoided the toxic and side effects of metronidazole, digestive tract reaction particularly, comprise nauseating, vomiting, inappetence, abdominal colic and neurotoxicity, more reduced the incidence rate of untoward reaction.
The specific embodiment:
For technological means, creation characteristic that the present invention is realized, reach purpose and effect is easy to understand, below in conjunction with specific embodiment, further set forth the present invention.
For the concordance of guarantee test result, the embodiment of the present invention has been used raw material, adjuvant, cillin bottle and the plug of same batch, and has adopted consistent production technology to prepare the ceftriaxone sodium pharmaceutical composition powder pin of injection.
Embodiment one, ceftriaxone for inj composition powder injection are in 1000
Prescription (specification: the 0.5g/ bottle):
Preparation technology:
Metronidazole lipid microsphere (in metronidazole) with recipe quantity directly is added in appropriate water for injection; Add the pH value of pH adjusting agent regulator solution to make it in the 6.5-6.8 scope after stirring and dissolving; Carry out the degerming circulating filtration, 30 minutes time by 0.45 μ m, 0.22 μ m filter membrane again; After pick test meets the requirements, solution is divided be filled in the rustless steel pallet, enter freeze drying box, carry out lyophilization and process, obtain the aseptic freeze-dried powder of metronidazole, pulverize and sieve; After the metronidazole lyophilized powder after pulverizing and sieving and the mixing of ceftriaxone sodium sterilized powder, after pick test meets the requirements, carry out packing according to labelled amount, namely get required sample.
Embodiment two, ceftriaxone for inj composition powder injection are in 1000
Prescription (specification: the 1.0g/ bottle):
Preparation technology:
Metronidazole lipid microsphere (in metronidazole) with recipe quantity directly is added in appropriate water for injection; Add the pH value of pH adjusting agent regulator solution to make it in the 6.5-6.8 scope after stirring and dissolving; Carry out the degerming circulating filtration, 30 minutes time by 0.45 μ m, 0.22 μ m filter membrane again; After pick test meets the requirements, solution is divided be filled in the rustless steel pallet, enter freeze drying box, carry out lyophilization and process, obtain the aseptic freeze-dried powder of metronidazole, pulverize and sieve; After the metronidazole lyophilized powder after pulverizing and sieving and the mixing of ceftriaxone sodium sterilized powder, after pick test meets the requirements, carry out packing according to labelled amount, namely get required sample.
Clinical data
In the patient who makes a definite diagnosis anaerobe and aerobe (to the aerobe of ceftriaxone sodium sensitivity) mixed infection, use A scheme (2 bottles/day of ceftriaxone for inj composition powder injections (1.0g/ bottle)) and B scheme (ceftriaxone sodium 2.0g/ day+metronidazole 2g/ day) GP TH, each is organized and divides equally 2 venoclysises every day, its Comprehensive Clinical curative effect and untoward reaction are as follows: total number of cases 125 examples of A scheme group, effective 120 examples, total effective rate is 96.0%, total number of cases 125 examples of B scheme group, effective 113 examples, total effective rate are 90.4%.
Adverse effect, wherein gastrointestinal reaction appears in the routine patient of A scheme group 4, show as epigastric discomfort, the side effect incidence rate is 3.20%, the untoward reaction of varying degree appears in B scheme group totally 9 examples, the side effect incidence rate is that 7.20%, A scheme group adverse reaction rate and degree are all lower than B scheme group.
Above demonstration and described ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description is only preference of the present invention; be not used for limiting the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.The claimed scope of the present invention is defined by appending claims and equivalent thereof.
Claims (4)
1. ceftriaxone sodium pharmaceutical composition, it is characterized in that, this pharmaceutical composition comprises ceftriaxone sodium and metronidazole lipid microsphere, the weight ratio of ceftriaxone sodium and metronidazole lipid microsphere is 100:3-100:10, the weight of metronidazole lipid microsphere is in metronidazole, this pharmaceutical composition is prepared into powder ampoule agent for injection, and the pH value of the aqueous solution of this pharmaceutical composition is 6.5-7.0.
2. ceftriaxone sodium pharmaceutical composition according to claim 1, it is characterized in that, in this pharmaceutical composition, the preferred weight ratio of ceftriaxone sodium and metronidazole lipid microsphere is 100:5, the weight of metronidazole lipid microsphere is in metronidazole, and the preferred pH value of the aqueous solution of this pharmaceutical composition is 6.5-6.8.
3. the described pharmaceutical composition of claim 1 or 2 is prepared into the method for powder ampoule agent for injection, it is characterized in that, the concrete steps of the method are:
(1) preparation metronidazole lipid microsphere
The crude drug component of preparation metronidazole lipid microsphere is:
The step of preparation metronidazole lipid microsphere is:
A) glycerol for injection and the poloxamer F-68 with recipe quantity is dissolved in water for injection, be placed in 80 ℃ of water bath with thermostatic control magnetic stirring apparatuss and be stirred to whole dissolvings, make mixture A, the injection water yield can be with abundant fused the getting final product of glycerol for injection and poloxamer F-68;
B) recipe quantity oleic acid is added in the oil phase that is consisted of by long-chain fat acid glyceride and medium chain length fatty acid triglyceride, forms and mix oil phase;
C) fabaceous lecithin and the metronidazole with recipe quantity adds in dehydrated alcohol 200ml, is stirred to fabaceous lecithin and metronidazole under 80 ℃ all after dissolving, and decompression volatilizes dehydrated alcohol, then adds the mixing oil phase, stirs and makes mixture B;
D) mixture A is added in mixture B, be placed in the 8000r/min of high-speed tissue mashing machine and stir 3 times, each 3min;
E) regulate pH value to 6.5-6.8, water for injection is settled to 1000ml, adds in high pressure homogenizer 70MPa homogenizing 8 times;
F) bottling, gland, 100 ℃ of sterilization 30min, the rapid cooling of ice-water bath and get final product, standby;
(2) with the metronidazole lipid microsphere of recipe quantity, directly be added in the water for injection of recipe quantity, the injection water yield can be dissolved the metronidazole lipid microsphere fully and be got final product;
(3) after stirring and dissolving the pH value of regulator solution in the 6.5-6.8 scope;
(4) and then by 0.45 μ m, 0.22 μ m filter membrane carry out the degerming circulating filtration, 30 minutes time;
(5) after pick test meets the requirements, solution is divided be filled in the rustless steel pallet, enter freeze drying box, carry out lyophilization and process, obtain the aseptic freeze-dried powder of metronidazole lipid microsphere, pulverize and sieve;
(6) metronidazole lipid microsphere lyophilized powder and the ceftriaxone sodium sterilized powder after pulverizing and sieving is mixed in proportion, and after pick test meets the requirements, carries out packing according to labelled amount, namely gets required powder ampoule agent for injection.
4. ceftriaxone sodium pharmaceutical composition according to claim 3 is prepared into the method for powder ampoule agent for injection, it is characterized in that: the specification that described ceftriaxone sodium pharmaceutical composition is prepared into powder ampoule agent for injection is 0.5g/ bottle and 1.0g/ bottle, and quality is in ceftriaxone.
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| CN2013100750018A CN103142615A (en) | 2013-03-08 | 2013-03-08 | Ceftriaxone sodium pharmaceutical composition and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104926834A (en) * | 2015-05-28 | 2015-09-23 | 浙江长典医药有限公司 | Ceftriaxone sodium compound entity for children and preparation for ceftriaxone sodium compound entity for children |
-
2013
- 2013-03-08 CN CN2013100750018A patent/CN103142615A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| 冯大林 等: "脂质微球给药系统的研究进展", 《现代医药卫生》 * |
| 赵尔贤: "甲硝唑配伍氧氟沙星与头孢曲松钠治疗急性化脓性阑尾炎临床分析", 《甘肃医药》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104926834A (en) * | 2015-05-28 | 2015-09-23 | 浙江长典医药有限公司 | Ceftriaxone sodium compound entity for children and preparation for ceftriaxone sodium compound entity for children |
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Application publication date: 20130612 |