CN103432137A - Medicinal composition of cefoxitin - Google Patents
Medicinal composition of cefoxitin Download PDFInfo
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- CN103432137A CN103432137A CN2013103812389A CN201310381238A CN103432137A CN 103432137 A CN103432137 A CN 103432137A CN 2013103812389 A CN2013103812389 A CN 2013103812389A CN 201310381238 A CN201310381238 A CN 201310381238A CN 103432137 A CN103432137 A CN 103432137A
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- cefoxitin
- ethanolamine
- sodium carbonate
- pharmaceutical composition
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- 229960002682 cefoxitin Drugs 0.000 title claims abstract description 72
- WZOZEZRFJCJXNZ-ZBFHGGJFSA-N cefoxitin Chemical group N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)CC1=CC=CS1 WZOZEZRFJCJXNZ-ZBFHGGJFSA-N 0.000 title claims abstract 5
- 239000000203 mixture Substances 0.000 title abstract description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 90
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims abstract description 86
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 39
- 239000000843 powder Substances 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 28
- 150000001875 compounds Chemical class 0.000 claims description 19
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 2
- 238000012360 testing method Methods 0.000 abstract description 42
- 239000012535 impurity Substances 0.000 abstract description 12
- 229920000642 polymer Polymers 0.000 abstract description 9
- 239000007924 injection Substances 0.000 abstract description 7
- 238000002347 injection Methods 0.000 abstract description 7
- 238000004090 dissolution Methods 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 238000012216 screening Methods 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 2
- 229940031098 ethanolamine Drugs 0.000 abstract 1
- 229940001593 sodium carbonate Drugs 0.000 abstract 1
- 238000013112 stability test Methods 0.000 abstract 1
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical group [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 description 70
- 239000000243 solution Substances 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 19
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 7
- 238000004140 cleaning Methods 0.000 description 7
- 238000007689 inspection Methods 0.000 description 7
- 239000011812 mixed powder Substances 0.000 description 7
- 238000012856 packing Methods 0.000 description 7
- 230000001954 sterilising effect Effects 0.000 description 7
- 238000004659 sterilization and disinfection Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 5
- 238000004811 liquid chromatography Methods 0.000 description 5
- 229920002307 Dextran Polymers 0.000 description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
- 229910000397 disodium phosphate Inorganic materials 0.000 description 4
- 235000019800 disodium phosphate Nutrition 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 229960003016 cefoxitin sodium Drugs 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000005286 illumination Methods 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
- 229930064664 L-arginine Natural products 0.000 description 2
- 235000014852 L-arginine Nutrition 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241001134775 Lysinibacillus fusiformis Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- -1 content descends Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002270 exclusion chromatography Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Abstract
The invention belongs to the technical field of medicines, discloses a medicinal composition of cefoxitin, and in particular relates to a medicinal composition containing cefoxitin, sodium carbonate and ethanol amine. The medicinal composition is obtained by a screening test; a dissolution speed test and clarity and medicine stability tests indicate that a powder injection prepared by the medicinal composition is high in re-dissolution speed, has qualified clarity, small content of impurities and cefoxitin polymer and high quality.
Description
Technical field
The invention belongs to medical technical field, be specifically related to the pharmaceutical composition that contains the active component cefoxitin.
Background technology
Cefoxitin acid (Cefoxitin), have another name called cefoxitin, chemistry is by name: be (6R, 7S)-3-carbamyl oxygen methyl-7-methoxyl group-8-oxo-7-[2-(2-thiazolyl) acetamido]-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid.Its chemical structural formula is as follows:
Cefoxitin was the medicine by U.S. MSD Corp. exploitation, introduced Chinese market in 1992, and the antibacterial activity in vitro research of anaerobe is all had to report at home and abroad.Result shows, cefoxitin all has good antibacterial action to bacteroid, anaerobic cocci, bacillus fusiformis and gram-negative facultatively anacrobic rod.There is result of study to show that cefoxitin has higher responsive coverage rate to bacterial strain, show that the cefoxitin antibacterial activity is very stable in the ever-increasing situation of bacterial drug resistance.This product clinical practice, in site infections such as responsive gram-negative bacteria and the lower respiratory tract due to anaerobe, genito-urinary system, ,Gu He joint, abdominal cavity, skin and soft tissues, also can be used for septicemia.
Now existing cefoxitin sodium for injection injectable powder type listing, for the aseptic raw material of cefoxitin sodium, through aseptic subpackaged forming, application is comparatively extensive at home.But cefoxitin sodium is unstable, responsive especially to illumination and temperature, easily be degraded into macromolecule impurity, content descends, and product (20 degree) under regulation storage requirement does not reach the quality standard requirement in the short period (3 months).And due to the increase of impurity, make adverse reaction rate clinically greatly improve, increased drug risk.
Summary of the invention
For these reasons, we study the pharmaceutical composition of finding a kind of new cefoxitin, this pharmaceutical composition contains cefoxitin acid, sodium carbonate and ethanolamine, research shows, the injectable powder that has this pharmaceutical composition to be prepared into, have advantages of that redissolution is fast, through stability study, shows, have better stability (impurity and cefoxitin polymer content change little), quality is more outstanding.
The present invention is achieved through the following technical solutions.
A kind of pharmaceutical composition containing the formula I compound, pharmaceutical composition contains formula I compound, sodium carbonate and ethanolamine, and the formula I compound is cefoxitin acid
Formula I.
A kind of pharmaceutical composition containing the formula I compound described above, wherein pharmaceutical composition is: formula I compound 1 weight portion, sodium carbonate and ethanolamine be the 0.25-0.35 weight portion altogether.Perhaps cefoxitin acid 1 weight portion, sodium carbonate and ethanolamine be the 0.25-0.35 weight portion altogether.
Above-mentioned a kind of pharmaceutical composition containing the formula I compound, wherein the weight ratio of sodium carbonate and ethanolamine is 1:0.25-0.75.
A kind of pharmaceutical composition containing the formula I compound described above, wherein the weight ratio of sodium carbonate and ethanolamine is 1:0.40
A kind of pharmaceutical composition containing the formula I compound described above, wherein the weight ratio of sodium carbonate and ethanolamine is 1:0.50.
A kind of pharmaceutical composition containing the formula I compound described above, wherein the weight ratio of sodium carbonate and ethanolamine is 1:0.60.
A kind of pharmaceutical preparation prepared containing the pharmaceutical composition of formula I compound described above.
A kind of pharmaceutical preparation prepared containing the pharmaceutical composition of formula I compound described above, wherein pharmaceutical preparation is injectable powder.
Annotate: cefoxitin acid of the present invention is purchased from vertical safe (lot number 20130411) (content 99.7%, maximum single impurity content 0.15%, total impurities content 0.55%, the cefoxitin polymer content 0.06%) of Shenzhen letter.
One, pharmaceutical composition screening test I
Test 1 group: cefoxitin acid 100g, sodium carbonate 30g.
Test 2 groups: cefoxitin acid 100g, sodium carbonate 20g, sodium hydrogen phosphate 10g.
Test 3 groups: cefoxitin acid 100g, sodium carbonate 20g, sodium citrate 10g.
Test 4 groups: cefoxitin acid 100g, sodium carbonate 20g, L-Histidine 10g.
Test 5 groups: cefoxitin acid 100g, sodium carbonate 20g, ethanolamine 10g.
Test 6 groups: cefoxitin acid 100g, sodium carbonate 20g, 1B 10g.
Test 7 groups: cefoxitin acid 100g, sodium carbonate 20g, ethylenediamine 10g.
Test 8 groups: cefoxitin acid 100g, sodium carbonate 20g, L-arginine 10g.
Preparation method: under aseptic condition, take respectively cefoxitin acid and the adjuvant of recipe quantity, mixed in three-dimensional mixer, after mixing half an hour, mix homogeneously.Under aseptic condition, by the cefoxitin acid that obtains and the mixed powder of adjuvant, be sub-packed in cleaning and, in the cillin bottle of sterilization treatment, loading amount is calculated as 1.0g/ by cefoxitin and props up, lid is rolled in tamponade, full inspection, qualified rear packing.
Dissolution velocity: sample thief, add the jolting of 12mL water for injection to entirely molten, use manual time-keeping simultaneously, recording dissolution time can not be over 5 minute.
Clarity: all meet the requirements according to two ones of pharmacopeia (version appendix in 2010) method sample for reference.
Result of the test: in Table 1.
The molten speed of the different groups of table 1 and clarity are relatively
The test brief summary: above-mentioned test shows, adopt sodium carbonate and sodium hydrogen phosphate, 1B, ethylenediamine, L-arginine as adjuvant, with cefoxitin, form pharmaceutical composition, be prepared into preparation, defective in dissolution velocity or clarity, and preparation prepared by other compositionss meets the requirements.
Two, pharmaceutical composition screening test II
Test method: get above-mentioned qualified preparation, place under 60 ℃ of high temperature, illumination (5000lx) condition 10 days, respectively at sampling and measuring impurity and polymer content after 5,10 days.
[impurity determination] measured according to high performance liquid chromatography (2010 editions two appendix V D of Chinese Pharmacopoeia).
Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filler; 0.2% triethylamine aqueous solution (V/V)-acetonitrile-glacial acetic acid (790:200:10) of take is mobile phase, and flow velocity is 1ml per minute; Detect wavelength 235nm.Number of theoretical plate is pressed the cefoxitin peak and is calculated, and should be no less than 2000.
It is appropriate that algoscopy is got this product, (take potassium dihydrogen phosphate 1.0g and sodium hydrogen phosphate 1.8g with the pH7.0 phosphate buffer, adding water 900ml dissolves, regulate pH7.0 ± 0.1 with potassium hydroxide, then be diluted with water to 1000ml) dissolve and be diluted in every 1ml solution containing 1mg as need testing solution; Getting need testing solution is diluted in every 1ml containing the solution of 0.01mg solution in contrast with the pH7.0 phosphate buffer.Get contrast solution 10 μ l injection liquid chromatographies, regulate detection sensitivity, make the peak height of main constituent be about 10% of full scale; Get each 10 μ l of need testing solution and contrast solution, injection liquid chromatography respectively, record to main constituent peak retention time 2.5 times of need testing solution chromatogram again.In the need testing solution chromatogram: in cefoxitin, any single impurity peak area must not be greater than 0.5 times (0.5%) of contrast solution main peak area, 3.0 times (3.0%) each impurity peak area and that must not be greater than contrast solution main peak area.
The cefoxitin polymer is measured according to molecular exclusion chromatography (two appendix of Chinese Pharmacopoeia version in 2010).
Chromatographic condition and sephadex G-10(40～120 μ m for system suitability) be filler; Be mobile phase A with 0.1mol/L phosphate buffer (get sodium hydrogen phosphate 21.85g and sodium dihydrogen phosphate 5.38g, add water 1000ml and dissolve, regulate pH value to 7.0), take water as Mobile phase B, flow velocity is about 1.0ml per minute, and the detection wavelength is 254nm.Take respectively mobile phase A, B is mobile phase, gets 0.1mg/ml blue dextran 2000 solution 200 μ l, the injection liquid chromatography, and number of theoretical plate calculates and all should be not less than 700 by blue dextran 2000 peaks, and tailing factor all should be less than 2.0.In two kinds of mobile phases, the ratio of blue dextran 2000 peak retention times should be between 0.93～1.07, and in contrast solution main peak and need testing solution, in polymer peak and corresponding chromatographic system, the ratio of blue dextran 2000 peak retention times all should be between 0.93～1.07.Separately take Mobile phase B as mobile phase, and precision measures contrast solution 200 μ l, continuous sample introduction 5 times, and the relative standard deviation of peak area should be not more than 5.0%.
The about 25mg of cefoxitin reference substance is got in the preparation of contrast solution, accurately weighed, is dissolved in water and quantitatively dilutes and make the solution that approximately contains 100 μ g in every 1ml.
Algoscopy is got the about 0.2g of this product, accurately weighed, puts in the 10ml measuring bottle, is dissolved in water and is diluted to scale, shakes up, and precision measures 200 μ l injection liquid chromatographies immediately, and the mobile phase A of take is measured as mobile phase, records chromatogram.Another precision measures contrast solution 200 μ l injection liquid chromatographies, take Mobile phase B as mobile phase, is measured in the same method.With calculated by peak area, containing the cefoxitin polymer, in cefoxitin, must not cross 0.5% by external standard method.
Result of the test: in Table 2, table 3.
Each test group preparation hot test result of table 2
Each test group preparation highlight test result of table 3
The test brief summary: above-mentioned test shows, while adopting sodium carbonate and ethanolamine as adjuvant, the cefoxitin preparation stability is better, and other groups do not meet prescription.
Three, pharmaceutical composition composite auxiliary material ratio screening test
Test 1 group: cefoxitin 100g, sodium carbonate 20g, ethanolamine 4g.
Test 2 groups: cefoxitin 100g, sodium carbonate 20g, ethanolamine 5g.
Test 3 groups: cefoxitin 100g, sodium carbonate 20g, ethanolamine 8g.
Test 4 groups: cefoxitin 100g, sodium carbonate 20g, ethanolamine 12g.
Test 5 groups: cefoxitin 100g, sodium carbonate 20g, ethanolamine 15g.
Test 6 groups: cefoxitin 100g, sodium carbonate 20g, ethanolamine 20g.
Preparation method: under aseptic condition, take respectively the cefoxitin acid of recipe quantity and natrium carbonicum calcinatum, ethanolamine, mixed in three-dimensional mixer, after mixing half an hour, mix homogeneously.Under aseptic condition, the cefoxitin acid that the first step is obtained and natrium carbonicum calcinatum, the mixed powder of ethanolamine, be sub-packed in cleaning and, in the cillin bottle of sterilization treatment, loading amount is calculated as 1.0g/ by cefoxitin and props up, and lid is rolled in tamponade, full inspection, qualified rear packing.
Test method: get above-mentioned qualified preparation, place under 60 ℃ of high temperature, illumination (5000lx) condition 10 days, respectively at sampling and measuring impurity and polymer content after 5,10 days.
Detection method is the same.
Result of the test: in Table 4 and table 5.
Each test group preparation hot test result of table 4
Each test group preparation highlight test result of table 5
The test brief summary: above-mentioned test shows, the sodium carbonate and the ethanolamine that are not any ratio can be as the adjuvants of cefoxitin, when the two ratio is not in the 1:0.25-0.75 scope, cefoxitin polymer or total impurities content in 10 days preparations are defective, therefore, we determine that the pharmaceutical composition used is: cefoxitin 1 weight portion, and sodium carbonate and ethanolamine 0.25-0.35 weight portion, wherein the weight ratio of sodium carbonate and ethanolamine is 1:0.25-0.75.
Preparation Example
Embodiment 1
Cefoxitin 1000g, sodium carbonate 200g, ethanolamine 50g.
Preparation method: under aseptic condition, take respectively the cefoxitin acid of recipe quantity and natrium carbonicum calcinatum, ethanolamine, mixed in three-dimensional mixer, after mixing half an hour, mix homogeneously.Under aseptic condition, the cefoxitin acid that the first step is obtained and natrium carbonicum calcinatum, the mixed powder of ethanolamine, be sub-packed in cleaning and, in the cillin bottle of sterilization treatment, loading amount is calculated as 1.0g/ by cefoxitin and props up, and lid is rolled in tamponade, full inspection, qualified rear packing.
Embodiment 2
Cefoxitin 1000g, sodium carbonate 200g, ethanolamine 80g.
Preparation method: under aseptic condition, take respectively the cefoxitin acid of recipe quantity and natrium carbonicum calcinatum, ethanolamine, mixed in three-dimensional mixer, after mixing half an hour, mix homogeneously.Under aseptic condition, the cefoxitin acid that the first step is obtained and natrium carbonicum calcinatum, the mixed powder of ethanolamine, be sub-packed in cleaning and, in the cillin bottle of sterilization treatment, loading amount is calculated as 1.0g/ by cefoxitin and props up, and lid is rolled in tamponade, full inspection, qualified rear packing.
Embodiment 3
Cefoxitin 1000g, sodium carbonate 200g, ethanolamine 100g.
Preparation method: under aseptic condition, take respectively the cefoxitin acid of recipe quantity and natrium carbonicum calcinatum, ethanolamine, mixed in three-dimensional mixer, after mixing half an hour, mix homogeneously.Under aseptic condition, the cefoxitin acid that the first step is obtained and natrium carbonicum calcinatum, the mixed powder of ethanolamine, be sub-packed in cleaning and, in the cillin bottle of sterilization treatment, loading amount is calculated as 1.0g/ by cefoxitin and props up, and lid is rolled in tamponade, full inspection, qualified rear packing.
Embodiment 4
Cefoxitin 1000g, sodium carbonate 200g, ethanolamine 120g.
Preparation method: under aseptic condition, take respectively the cefoxitin acid of recipe quantity and natrium carbonicum calcinatum, ethanolamine, mixed in three-dimensional mixer, after mixing half an hour, mix homogeneously.Under aseptic condition, the cefoxitin acid that the first step is obtained and natrium carbonicum calcinatum, the mixed powder of ethanolamine, be sub-packed in cleaning and, in the cillin bottle of sterilization treatment, loading amount is calculated as 1.0g/ by cefoxitin and props up, and lid is rolled in tamponade, full inspection, qualified rear packing.
Embodiment 5
Cefoxitin 1000g, sodium carbonate 200g, ethanolamine 150g.
Preparation method: under aseptic condition, take respectively the cefoxitin acid of recipe quantity and natrium carbonicum calcinatum, ethanolamine, mixed in three-dimensional mixer, after mixing half an hour, mix homogeneously.Under aseptic condition, the cefoxitin acid that the first step is obtained and natrium carbonicum calcinatum, the mixed powder of ethanolamine, be sub-packed in cleaning and, in the cillin bottle of sterilization treatment, loading amount is calculated as 1.0g/ by cefoxitin and props up, and lid is rolled in tamponade, full inspection, qualified rear packing.
The foregoing is only preferred embodiment of the present invention, in order to limit the present invention, within the spirit and principles in the present invention not all, any modification of doing, be equal to replacement, improvement etc., within all should being included in protection scope of the present invention.
Claims (8)
1. the pharmaceutical composition containing the formula I compound, is characterized in that pharmaceutical composition contains formula I compound, sodium carbonate and ethanolamine, and wherein formula I is cefoxitin acid
Formula I.
2. a kind of pharmaceutical composition containing the formula I compound according to claim 1, wherein pharmaceutical composition is: formula I compound 1 weight portion, sodium carbonate and ethanolamine be the 0.25-0.35 weight portion altogether.
3. a kind of pharmaceutical composition containing the formula I compound according to claim 1 and 2, wherein the weight ratio of sodium carbonate and ethanolamine is 1:0.25-0.75.
4. a kind of pharmaceutical composition containing the formula I compound according to claim 1 and 2, wherein the weight ratio of sodium carbonate and ethanolamine is 1:0.40.
5. a kind of pharmaceutical composition containing the formula I compound according to claim 1 and 2, wherein the weight ratio of sodium carbonate and ethanolamine is 1:0.50.
6. a kind of pharmaceutical composition containing the formula I compound according to claim 1 and 2, wherein the weight ratio of sodium carbonate and ethanolamine is 1:0.60.
7. a kind of pharmaceutical preparation prepared containing the pharmaceutical composition of formula I compound according to claim 1 and 2.
8. a kind of pharmaceutical preparation prepared containing the pharmaceutical composition of formula I compound according to claim 7, wherein pharmaceutical preparation is injectable powder.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4582830A (en) * | 1982-09-10 | 1986-04-15 | Glaxo Group Limited | Pharmaceutical compositions |
| CN101941983A (en) * | 2010-09-25 | 2011-01-12 | 海南天煌制药有限公司 | Preparation method of high-purity cefoxitin sodium |
| CN102755325A (en) * | 2012-07-04 | 2012-10-31 | 深圳信立泰药业股份有限公司 | Cefoxitin sodium medicinal composition, powder injection and preparation method thereof |
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2013
- 2013-08-28 CN CN201310381238.9A patent/CN103432137B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4582830A (en) * | 1982-09-10 | 1986-04-15 | Glaxo Group Limited | Pharmaceutical compositions |
| CN101941983A (en) * | 2010-09-25 | 2011-01-12 | 海南天煌制药有限公司 | Preparation method of high-purity cefoxitin sodium |
| CN102755325A (en) * | 2012-07-04 | 2012-10-31 | 深圳信立泰药业股份有限公司 | Cefoxitin sodium medicinal composition, powder injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 李捷玮，等: "《常用药物辅料手册》", 30 June 2000, article "《二乙醇胺、三乙醇胺》", pages: 91-92 - 287-288 * |
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