CN101647800B - Combination of cefuroxime sodium - Google Patents
Combination of cefuroxime sodium Download PDFInfo
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- CN101647800B CN101647800B CN2009101628271A CN200910162827A CN101647800B CN 101647800 B CN101647800 B CN 101647800B CN 2009101628271 A CN2009101628271 A CN 2009101628271A CN 200910162827 A CN200910162827 A CN 200910162827A CN 101647800 B CN101647800 B CN 101647800B
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- cefuroxime
- sodium
- acid
- arginine
- test
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- URDOHUPGIOGTKV-JTBFTWTJSA-M Cefuroxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 URDOHUPGIOGTKV-JTBFTWTJSA-M 0.000 title abstract description 27
- 229960000534 cefuroxime sodium Drugs 0.000 title abstract description 27
- 239000004475 Arginine Substances 0.000 claims abstract description 35
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000000203 mixture Substances 0.000 claims abstract description 26
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 229960001668 cefuroxime Drugs 0.000 claims description 66
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 claims description 66
- 239000007924 injection Substances 0.000 claims description 16
- 238000002347 injection Methods 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 7
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- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 abstract description 2
- 239000003086 colorant Substances 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 41
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- 241000283973 Oryctolagus cuniculus Species 0.000 description 15
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
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- 206010070834 Sensitisation Diseases 0.000 description 6
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- 229940124587 cephalosporin Drugs 0.000 description 4
- 150000001780 cephalosporins Chemical class 0.000 description 4
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- -1 methoxyimino Chemical group 0.000 description 4
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
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- KLCDQSGLLRINHY-UHFFFAOYSA-N 1-phenyldiazenylnaphthalen-2-amine Chemical compound NC1=CC=C2C=CC=CC2=C1N=NC1=CC=CC=C1 KLCDQSGLLRINHY-UHFFFAOYSA-N 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 240000007711 Peperomia pellucida Species 0.000 description 2
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
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- 239000002085 irritant Substances 0.000 description 2
- 231100000021 irritant Toxicity 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 235000017166 Bambusa arundinacea Nutrition 0.000 description 1
- 235000017491 Bambusa tulda Nutrition 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
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- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
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- HDFXRQJQZBPDLF-UHFFFAOYSA-L disodium hydrogen carbonate Chemical compound [Na+].[Na+].OC([O-])=O.OC([O-])=O HDFXRQJQZBPDLF-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
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- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to a combination of cefuroxime sodium, which is characterized in that the combination is combination of the cefuroxime sodium and arginine. A preparation method comprises the following steps: under the bacteria-free environment, bacteria-free raw materials of the cefuroxime sodium and the arginine are weighed according to a prescription proportion to be uniformly mixed, and then the mixture is separately packed. The combination solves problems that the active components of cefuroxime sodium is not insoluble in water, the original medicament of cefuroxime sodium is unstable, and products are unqualified caused by easy standard exceeding of colors, and can be preserved, stored and transported under the shady and cool condition.
Description
Invention field
The invention belongs to medical technical field, relate to a kind of compositions of antibiotic cefuroxime acid.
Background technology
Cefuroxime acid
Chemical name: (6R, 7R)-7-[2-furyl (methoxyimino) acetylamino]-3-carbamyl oxygen methyl-8-oxo-5-thia-1-azabicyclic [4.2.0] oct-2-ene-2-formic acid.
Molecular formula: C16H16N4O8S
Molecular weight: 424.37
Cefuroxime acid is a second generation cephalosporin class antibiotic, and efficient, low toxicity, wide spectrum since listing in 1975, have obtained extensive use.
With its sodium salt, promptly Cefuroxime Sodium uses by vein or intramuscular injection clinically.
The Cefuroxime Sodium chemical name: (6R, 7R)-7-[2-furyl (methoxyimino) acetylamino]-3-carbamyl oxygen methyl-8-oxo-5-thia-1-azabicyclic [4.2.0] oct-2-ene-2-formic acid sodium salt
Chemical structural formula:
Molecular formula: C16H15N4NaO8S
Molecular weight: 446.37
Cefuroxime acid is the active component of Cefuroxime Sodium, and is water-soluble hardly, uses for convenient injection clinically, therefore makes pharmaceutical dosage forms with its sodium salt.
Domestic have many enterprises to produce Cefuroxime Sodium crude drug and preparation, and Cefuroxime Sodium is one of domestic most popular cephalosporins, and year use amount is above 500 tons.
Research to Cefuroxime Sodium is also many, and multinomial relevant patent is arranged, and concentrates on the process patent of technology, route basically, and the compositions patent formed of Cefuroxime Sodium and enzyme inhibitor.
The Cefuroxime Sodium instability changes soon in storage, and outstanding behaviours is that change color is fast, and color flavescence especially easily, intensification are accompanied by change color, and also showing related substance increases content decline.
But color is distinct issues, is to solve color problem, and a lot of people have done a lot of research, this are had more detailed description at patent CN200910036828.1, but how to concentrate on basically by improving the crystallization of Cefuroxime Sodium, improves on the product stability.
Be to guarantee product quality, 2005 editions requirements of Chinese Pharmacopoeia, the cefuroxime preparation of sodium is preserved at cold place, causes storing, transports all very inconvenient, and especially some small towns Medical Depots, hospital, clinic do not possess the freezer of such condition, and use is very restricted.
We find that under study for action the cefuroxime acid intrinsic colour is very shallow, and is almost colourless, but in the process that becomes sodium salt, be easy to flavescence, color burn, concrete reason is not clear, and is all relevant with the selection of the pH value of the temperature of the importing of sodium ion, reaction, solution, salt forming agent from research.
Cephalosporins is because of the characteristics of structure itself, and is more stable under acid condition, less stable under the alkali condition, and cefuroxime acid itself is also more stable than Cefuroxime Sodium.
Cefuroxime acid directly is not used as pharmaceutical preparation, be because water insoluble, so we are from another angle thinking, solve the solubility problem of cefuroxime acid, the advantage that keeps its good stability, a series of cefuroxime acid composition has been screened in design, finds the cefuroxime acid arginine composition, both can solve the stability problem of Cefuroxime Sodium, can solve the solubility problem of cefuroxime acid again.
Goal of the invention
The object of the present invention is to provide the more stable cefuroxime acid composition of a kind of product quality, to overcome its existing pharmaceutical preparation Cefuroxime Sodium poor stability, color is easy to exceed standard, and the shortcoming of storage, traffic condition harshness can solve the water-fast problem of cefuroxime acid again.
The invention has the advantages that: said composition can solve the problem that cefuroxime acid is insoluble in water, also can solve former medicine Cefuroxime Sodium problem of unstable, need not cold place and preserves, convenient storing.
The result shows through medicine stability test (40 ℃ of accelerated tests 1 month, see example 1 investigate the result): the color of said composition solution 0 day is less than yellow No. 1, and quickening after one month be No. 3, yellow, and conformance with standard is stipulated requirement; And the color of cefuroxime sodium solution was quickened after one month at yellow No. 2 in 0 day, was yellow No. 10.Its colour index has not met standard code.The variation of this compositions related substance does not obviously have Cefuroxime Sodium fast yet simultaneously, illustrates that stability is obviously good than Cefuroxime Sodium.Other index, also variant as moisture content, pH value, content is obviously different, is because said composition contains arginic reason.
Cefuroxime preparation of sodium problem of unstable mainly reflects by colour index, and underproof reason all is because color exceeds standard basically.For ensuring the quality of products, so must preserve at cold place, use, transport very inconvenient, estimate that the present invention when keeping the cefuroxime acid good antibacterial activity, has solved solubility problem, improved product stability, expectation is accumulating easily, and important and practical meanings is arranged.
Sodium carbonate, sodium bicarbonate or other organic amine, also can solve the solubility problem of cefuroxime acid, but find, sodium carbonate and sodium bicarbonate and cefuroxime acid are formed compositions, and meeting aerogenesis when being dissolved in water uses inconvenient, and the solution colour that obtains is deep, at PH is under the neutral condition, and solution colour is at yellow No. 3, and reason may be relevant with sodium ion importing and sodium carbonate sodium bicarbonate exothermic dissolution.
And at present as the adjuvant of injection cephalosporins, as cosolvent or PH regulator, what use at present is exactly sodium carbonate and arginine, so other organic amine salt can be considered use, but faces the problem of safety.So take all factors into consideration, arginine is the most suitable.
The cefuroxime acid arginine composition preparation of following example 1, intravascular irritant experiment, hemolytic experiment, anaphylaxis experiment confirm, said composition does not have blood vessel irritation, hemolytic and sensitization, is fit to make injection.
Said composition has solved the problem that cefuroxime acid is insoluble in water, is fit to be prepared into ejection preparation, and stable in properties need not cold place storage, has made things convenient for use.
The content of its impurity also can effectively reduce simultaneously, and expectation can reduce side reaction such as anaphylactoid incidence rate, and important clinical application value should be arranged.
Summary of the invention
The invention provides a kind of cefuroxime acid and arginic compositions.Concrete method for making is: under gnotobasis, takes by weighing cefuroxime acid and arginic sterile bulk drug, pours in the high efficient mixed machine behind the abundant mix homogeneously according to the prescription ratio, and packing, promptly.
Change aseptic powder injection preparation packing workshop over to, it is distributed into single antibiotic formulations by specification.
The specific embodiment
Further set forth the present invention below by embodiment, but do not limit the present invention.
Embodiment 1
Commercially available aseptic cefuroxime sodium raw materials 50kg, stir under 5 ℃ and be dissolved in 500 liters of waters for injection activated carbon decolorizing, aseptic filtration, filtrate is stirred 10% hydrochloric acid solution 41kg after following slow stream adds aseptic filtration, add the back and continue to stir 40 minutes, and rise to room temperature, filter, precipitation is washed 3 times for 30 liters with water for injection, drain, vacuum drying gets about 45 kilograms of aseptic cefuroxime acid.
In aseptic batch plant, take by weighing aseptic cefuroxime acid crude drug 35.5kg and arginine crude drug 14.5kg, pour in the efficient three-dimensional motion mixer, be 5 rev/mins with rotating speed and mixed about 1.5 hours, behind the mix homogeneously, discharging, Aluminum Drum packing.
The cefuroxime acid arginine raw material of Aluminum Drum packing is transferred to sterile preparation packing workshop, (it is pure in cefuroxime acid to give money as a gift by 0.5g, 1.0g specification, 0.5g the about 0.71g of loading amount, the about 1.42g of 1.0g loading amount) divide and be filled in the aseptic antibiotic glass bottle, the preparation finished product.
The above-mentioned cefuroxime acid arginine formulations that makes, cefuroxime preparation of sodium with commercially available cefuroxime sodium raw materials direct packaging, press project and 0 day experimental data of method detection under 2005 editions cefuroxime sodium for injection items of Chinese Pharmacopoeia, and the experimental data after 40 ℃ of accelerated tests 1 month (40 ℃ of temperature are in humidity 75% climatic chamber).
Experimental result is as follows:
| Test item | Preparation of the present invention (1.0g lot number 090601) 0 day | Preparation of the present invention (1.0g lot number 090601) 40 | Cefuroxime preparation of sodium sky | The cefuroxime preparation of sodium quickened one month for 40 ℃ |
| Quickened one month | ||||
| Character | White crystalline powder | The off-white color crystalline powder | The off-white color crystalline powder | Light yellow crystalline powder |
| Moisture content | 0.5％ | 0.6％ | 2.5％ | 2.9％ |
| PH value | 6.8 | 6.9 | 7.3 | 7.6 |
| Solution colour | Less than yellow No. 1 | Yellow No. 3 | Yellow No. 2 | Yellow No. 10 |
| Clarity | Clarification | Clarification | Clarification | Less than No. 1 |
| Content | 70.3％ | 70.1％ | 94.2％ | 92.8％ |
| Maximum single assorted | 0.1％ | 0.2％ | 0.1％ | 0.5％ |
| Total assorted | 0.2％ | 0.5％ | 0.2％ | 1.2％ |
| Polymer | 0.1％ | 0.1％ | 0.1％ | 0.2％ |
| Aseptic | Qualified | Qualified | Qualified | Qualified |
| Endotoxin | Qualified | Qualified | Qualified | Qualified |
In the above-mentioned data, there are bigger difference in preparation of the present invention and Cefuroxime Sodium formulation content, are that the cefuroxime preparation of sodium is the reason of cefuroxime sodium salt because preparation of the present invention contains arginine.
Experimental result shows, 40 ℃ of accelerated tests 1 month, and cefuroxime preparation of sodium against regulation (the color project exceeds standard), the variation of its related substance is obviously fast than the present invention preparation simultaneously.Preparation of the present invention is more stable than Cefuroxime Sodium, has especially improved the color key index of solution.
Also to above-mentioned composition cefuroxime acid arginine formulations, carried out blood vessel irritation, hemolytic and sensitization experiment, laboratory report is as follows:
Cefuroxime for inj acid arginine blood vessel irritant test
Summary
This experimental observation the zest of cefuroxime for inj acid arginine to the rabbit blood vessel.Result of the test shows: cefuroxime for inj acid arginine rabbit vein drug administration by injection, 2 times/d, successive administration 3 days does not have the obvious stimulation effect to the rabbit auricular vein.
Test objective
This test is intended to observe this product rabbit every day auricular vein drug administration by injection 2 times, for three days on end, the rabbit auricular vein is had or not the vascular stimulation effect, for clinical practice safety provides reference.
Test material
1. be subjected to the reagent thing: cefuroxime for inj acid arginine, specification: 1.0g/ bottle (cefuroxime 1g, arginine 0.41g), lot number: 090601; Provide by Beijing Lianmu Medical Technology Development Co., Ltd..During test medicine is made into 7.5% clinical working concentration with sterilized water for injection.Sodium chloride injection.
2. animal and raising: new zealand rabbit, the male and female dual-purpose provides the quality certification by Beijing medical courses in general institute Experimental Animal Center:, carry out the pre-raising of two weeks after buying, 2.3～2.6kg when being used to test.Raising condition: raise with the metal rabbit-hutch, freely drink water, give pellet, 22～25 ℃ of room temperatures, humidity about 60%.
Test method and observation index
Get 6 of health, ear edge not damaged rabbit, be divided into two groups at random, be i.e. cefuroxime for inj acid arginine group and sodium chloride injection matched group, 3 every group by body weight.This product clinical dosage is about 4g/ people/d, divides 2 times intravenous administration, counts 66.7mg/kg by adult 60kg.In view of the above, it is 266.7mg/kg (3.56ml/kg) that cefuroxime for inj acid arginine group dosage is established in this test, divide to give for 2 times, and successive administration 3d, with aseptic manipulation auricular vein drug administration by injection, matched group gives the equivalent sodium chloride injection respectively.
After administration every day, the red and swollen situation of partial vein blood vessel of perusal administration and surrounding tissue.Animal was knocked head in 24 hours after the last administration and put to death,, use 10% formaldehyde fixed respectively at injection site proximal part 1.5cm to 3cm place clip ear edge, the conventional organization section, observation has or not thrombosis, endothelial injury and other pathological change.
Result of the test
During the administration and behind the last medication 24h, blood vessel and surrounding tissue redness are not seen in perusal, and the visible rabbit ear blood vessel of tissue slice inspection is complete, does not see endothelial injury, surrounding tissue does not have edema and inflammatory cell infiltration, compares no significant difference with sodium chloride injection group rabbit ear blood vessel.
Conclusion (of pressure testing)
Cefuroxime for inj acid arginine rabbit auricular vein drug administration by injection, 2 times/d, for three days on end, rabbit auricular vein blood vessel there is not the obvious stimulation effect, also do not cause the obvious pathological changes of blood vessel surrounding tissue.
Cefuroxime for inj acid arginine hemolytic test
Summary
This experimental observation cefuroxime for inj acid arginine to the erythrocytic haemolysis of rabbit.The result shows: under this experimental condition, cefuroxime for inj acid arginine does not have obvious external haemolysis and causes agglutination tame rabbit erythrocyte.
Test objective
This test is intended to observe this product man rabbit erythrocyte is had or not haemolysis and agglutination, for clinical practice provides reference.
Test material
1. be subjected to reagent thing source and compound method the same.
2. animal and raise the same.
3. instrument: LXJ-II type centrifugal precipitation mechanism, medical analytical instrument factory in Shanghai produces; HH-W21-600 type thermostat water bath, the medical thermostatic equipment in Shanghai factory produces.
Test method
The preparation of 2% rabbit erythrocyte suspension: rabbit heart extracting blood 10ml, put in the beaker and stir the removal fibrin with bamboo let, getting equivalent then moves in 2 10ml graduated centrifuge tubes, each adds normal saline 5ml, behind the mixing centrifugal 5 minutes (2500rpm), remove supernatant, it is centrifugal to add normal saline 5ml mixing again, cyclic washing is to the supernatant water white transparency.The gained erythrocyte is standby with the suspension that normal saline is diluted to 2% (V/V).
Operating procedure: get 7 in test tube, add cefuroxime for inj acid arginine (clinical concentration) solution 0.1,0.2,0.3,0.4 and 0.5ml respectively by table 1, the 6th pipe does not add and is subjected to test product, as blank, the 7th pipe does not still add and is subjected to test product, replace normal saline with distilled water, as hemolytic positive control.Each pipe is shaken up gently, and insulation is 4 hours in 37 ℃ of water-baths, observes each pipe and has or not haemolysis.
The external hemolytic test application of sample of table 1 table
Observation index and result judge: respectively manage the haemolysis situation respectively at insulation perusal in 0.5,1,2,3,4 hour, whether available in case of necessity microscopic examination erythrocyte breaks.With 0.3ml tried thing (the 3rd pipe) but the person that do not cause the haemolysis in 2 hours thinks injection.Criterion is referring to table 2 as a result.
Table 2 erythrocyte hemolysis, coagulation criterion
Result of the test
Haemolysis appearred at once after positive control pipe (No. 7 pipes) added distilled water.After adding cefuroxime for inj acid arginine (clinical concentration) solution, 0.5-1 hour, 1-6 number the pipe erythrocyte began to sink the supernatant liquid achromatism and clarity; 2 hours, 1-6 number pipe supernatant achromatism and clarity, a large amount of erythrocyte are sunken to the pipe end; 3 hours, 1-6 number pipe supernatant achromatism and clarity, a large amount of erythrocyte are sunken to the pipe end; 4 hours, 1-6 number pipe solution erythrocyte sank in a large number, the supernatant liquid achromatism and clarity, and the pipe end, have a small amount of erythrocyte residual.The visible red cell evenly scatters after the jolting, proves no red blood cell condensation.(seeing Table 3)
Table 3 cefuroxime for inj acid arginine hemolytic test result
In the table :-no haemolysis+full haemolysis, negative tube is a normal saline; Positive pipe is distilled water
Conclusion (of pressure testing)
This experimental observation cefuroxime for inj acid arginine to the erythrocytic haemolysis of rabbit.Result of the test shows: cefuroxime for inj acid arginine does not have obvious external haemolysis and causes agglutination tame rabbit erythrocyte.
Cefuroxime for inj acid arginine hypersensitive test
Summary
This experimental observation the allergenic effect of cefuroxime for inj acid arginine to Cavia porcellus.Result of the test shows: under this experimental condition, cefuroxime for inj acid arginine does not have sensitization to animal subject.
Test objective
This test is intended to investigate this product and has or not allergenic effect, is reference data for clinical drug use.
Test material
1. be subjected to reagent thing source and reagent the same, trial test shows that this product can cause Cavia porcellus death more than 0.19% concentration, so the concentration of compounding pharmaceutical 0.19% is used for test.
2. positive reference substance: ovalbumin provides the import packing of Sigma company by the biological company limited of couple stars.Being mixed with 0.4% concentration with normal saline is for experiment.
3. animal: albino guinea-pig, male and female half and half are provided by Beijing medical courses in general institute Experimental Animal Center, carry out for two weeks after buying and raise body weight 270-300g when being used to test in advance.Raising condition: raise with metal cage, freely drink water, give pellet, 22～25 ℃ of room temperatures, humidity about 60%.
Test method and observation index
Get healthy guinea pig, be divided into cefuroxime for inj acid arginine group, ovalbumin positive controls and sodium chloride injection negative control group, 6 every group at random by body weight.
Animal subject sensitization: i.p. cefuroxime for inj acid arginine, 0.4% ovalbumin and sodium chloride injection respectively by the sterile working next day, 0.5ml/ only, totally three sensitization.
Attack: each treated animal is divided into 2 batches, 3 every batch, a collection of after injection is subjected to reagent first intravenous injection in 14 days only attacked by test product 1ml/; Another batch the 21st day intravenous injection 1ml/ after first administration only attacks.
After attacking administration, in the 15min, observe animal and have or not cough, grab nose, erect situations such as hair, dyspnea, spasm, shock and death, and press the listed standard scoring of table 4.
Table 4 systemic anaphylaxis reaction standards of grading
The result judges: marked 〉=2 o'clock, and be the hypersensitive test positive.
Result of the test
Twice challenge trial result is all negative for cefuroxime for inj acid arginine.And positive controls can make animal subject performances such as nose, perpendicular hair, dyspnea, spasm, shock death occur grabbing.Hypersensitive test result is referring to table 5.
Table 5 cefuroxime for inj acid arginine hypersensitive test result
Conclusion (of pressure testing)
This experimental observation the allergenic effect of cefuroxime for inj acid arginine drug administration by injection to Cavia porcellus.Result of the test shows: under this experimental condition, cefuroxime for inj acid arginine does not have sensitization to animal subject.
Claims (1)
1. the compositions of a cefuroxime acid, it is characterized in that said composition is cefuroxime acid and arginic combination, described cefuroxime acid and arginic weight ratio are 1: 0.41, and make injection powder injection by the following method: in aseptic batch plant, take by weighing aseptic cefuroxime acid crude drug and arginine crude drug, pour in the efficient three-dimensional motion mixer, being 5 rev/mins with rotating speed mixed 1.5 hours, mix homogeneously gets cefuroxime acid arginine raw material, in sterile preparation packing workshop, be filled in the aseptic antibiotic glass bottle promptly by 0.5g or 1.0g specification branch.
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| CN101007811A (en) * | 2007-01-16 | 2007-08-01 | 陈文展 | Organic amine salt of cephalosporin compound and its preparation method |
| CN101129382A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing beta-lactam antibiotic and buffering component |
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| CN101129382A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing beta-lactam antibiotic and buffering component |
| CN101007811A (en) * | 2007-01-16 | 2007-08-01 | 陈文展 | Organic amine salt of cephalosporin compound and its preparation method |
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| Title |
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| 詹少锦等.头孢他啶不同助溶剂之比较.《广东药学》.2005,第15卷(第3期),参见第68-69页. * |
| 陈振阳等.注射用盐酸头孢吡肟处方研究.《现代食品与药品杂志》.2006,第16卷(第1期),参见第53页左栏第1-2段,摘要. * |
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