CN101590061B - Medicinal composition of cefotetan disodium - Google Patents
Medicinal composition of cefotetan disodium Download PDFInfo
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- CN101590061B CN101590061B CN2009101068335A CN200910106833A CN101590061B CN 101590061 B CN101590061 B CN 101590061B CN 2009101068335 A CN2009101068335 A CN 2009101068335A CN 200910106833 A CN200910106833 A CN 200910106833A CN 101590061 B CN101590061 B CN 101590061B
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- cefotetan disodium
- cefotetan
- glucose
- disodium
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- ZQQALMSFFARWPK-ZTQQJVKJSA-L cefotetan disodium Chemical group [Na+].[Na+].N([C@]1(OC)C(N2C(=C(CSC=3N(N=NN=3)C)CS[C@@H]21)C([O-])=O)=O)C(=O)C1SC(=C(C(N)=O)C([O-])=O)S1 ZQQALMSFFARWPK-ZTQQJVKJSA-L 0.000 title claims abstract description 87
- 229960004445 cefotetan disodium Drugs 0.000 title claims abstract description 86
- 239000000203 mixture Substances 0.000 title claims abstract description 45
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 55
- 239000008103 glucose Substances 0.000 claims description 55
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 23
- 239000002671 adjuvant Substances 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 9
- 229930195725 Mannitol Natural products 0.000 claims description 9
- 238000004108 freeze drying Methods 0.000 claims description 9
- 239000000594 mannitol Substances 0.000 claims description 9
- 235000010355 mannitol Nutrition 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 19
- 238000000034 method Methods 0.000 abstract description 9
- 230000008569 process Effects 0.000 abstract description 9
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000003860 storage Methods 0.000 abstract description 5
- 239000004615 ingredient Substances 0.000 abstract 3
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 238000005728 strengthening Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 description 25
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000000047 product Substances 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 10
- 229960005495 cefotetan Drugs 0.000 description 9
- SRZNHPXWXCNNDU-RHBCBLIFSA-N cefotetan Chemical compound N([C@]1(OC)C(N2C(=C(CSC=3N(N=NN=3)C)CS[C@@H]21)C(O)=O)=O)C(=O)C1SC(=C(C(N)=O)C(O)=O)S1 SRZNHPXWXCNNDU-RHBCBLIFSA-N 0.000 description 9
- 229930186147 Cephalosporin Natural products 0.000 description 8
- 229940124587 cephalosporin Drugs 0.000 description 8
- 150000001780 cephalosporins Chemical class 0.000 description 8
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
- 239000008101 lactose Substances 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 6
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 102000006635 beta-lactamase Human genes 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000008215 water for injection Substances 0.000 description 6
- 230000003115 biocidal effect Effects 0.000 description 5
- 238000002386 leaching Methods 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 108090000204 Dipeptidase 1 Proteins 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000012856 packing Methods 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940090044 injection Drugs 0.000 description 3
- 108020004256 Beta-lactamase Proteins 0.000 description 2
- LXWBXEWUSAABOA-UHFFFAOYSA-N Cephamycin-C Natural products S1CC(COC(N)=O)=C(C(O)=O)N2C(=O)C(OC)(NC(=O)CCCC(N)C(O)=O)C21 LXWBXEWUSAABOA-UHFFFAOYSA-N 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 2
- 229940106164 cephalexin Drugs 0.000 description 2
- LXWBXEWUSAABOA-VXSYNFHWSA-N cephamycin C Chemical compound S1CC(COC(N)=O)=C(C(O)=O)N2C(=O)[C@@](OC)(NC(=O)CCC[C@@H](N)C(O)=O)[C@H]21 LXWBXEWUSAABOA-VXSYNFHWSA-N 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 241000187390 Amycolatopsis lactamdurans Species 0.000 description 1
- 206010061695 Biliary tract infection Diseases 0.000 description 1
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [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 1
- 241000588923 Citrobacter Species 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 206010014568 Empyema Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010061977 Genital infection female Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241001655322 Streptomycetales Species 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 230000003103 anti-anaerobic effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229960004841 cefadroxil Drugs 0.000 description 1
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 description 1
- 229960003585 cefmetazole Drugs 0.000 description 1
- SNBUBQHDYVFSQF-HIFRSBDPSA-N cefmetazole Chemical compound S([C@@H]1[C@@](C(N1C=1C(O)=O)=O)(NC(=O)CSCC#N)OC)CC=1CSC1=NN=NN1C SNBUBQHDYVFSQF-HIFRSBDPSA-N 0.000 description 1
- 229960004261 cefotaxime Drugs 0.000 description 1
- AZZMGZXNTDTSME-JUZDKLSSSA-M cefotaxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 AZZMGZXNTDTSME-JUZDKLSSSA-M 0.000 description 1
- 229940017050 cefotetan injection Drugs 0.000 description 1
- 229960002682 cefoxitin Drugs 0.000 description 1
- DKOQGJHPHLTOJR-WHRDSVKCSA-N cefpirome Chemical compound N([C@@H]1C(N2C(=C(C[N+]=3C=4CCCC=4C=CC=3)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 DKOQGJHPHLTOJR-WHRDSVKCSA-N 0.000 description 1
- 229960000466 cefpirome Drugs 0.000 description 1
- 229960004755 ceftriaxone Drugs 0.000 description 1
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- -1 methoxyl group Chemical group 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a medicinal composition of cefotetan disodium, which comprises the cefotetan disodium, and also comprises minor ingredients; the percentage by mass of the cefotetan disodium is 50 to 99 percent; and the percentage by mass of the minor ingredients is 1 to 50 percent. The medicinal composition of the cefotetan disodium is added with the minor ingredients capable of strengthening the stability of the cefotetan disodium to inhibit the quick degradation of the cefotetan disodium when the cefotetan disodium meets water in the processes of production, storage and use and improve the stability of the cefotetan disodium, so that a high-efficiency and stable medicinal composition product of the cefotetan disodium is obtained.
Description
Technical field
The present invention relates to a kind of medicine, relate in particular to a kind of pharmaceutical composition of Cefotetan Disodium of injection.
Background technology
Existing more at present cephalosporins listing is widely used in clinical, and the treatment that catches is played an important role.But analyze, the cephalosporins that has gone on the market mostly is cephalosporin (Cephalosporin) class.Cefotaxime from the cefalexin of the first generation, cefadroxil to a new generation, ceftriaxone, cefpirome etc., though each respectively has characteristics for cephalosporins, but such antibiotic common limit that lacks is a beta-lactamase instability to some Production by Bacteria, therefore can produce the therapeutic effect that infects due to the bacterial strain of beta-lactamase to some and be affected.After in streptomycete (S.Lactamdurans), finding cephamycin C (Cephamycin C), transform side chain and obtain some cephamycin-type antibiotic medicines through synthetic modification.This type of antibiotic structurally is different from cephalosporins, a trans methoxyl group is arranged on 7 carbon atoms, though its antibacterial action is lower than the first generation cephalosporin class to the effect of gram positive bacteria, but to gram negative bacteria antibacterial action excellence, anti-beta-lactamase (comprising the gram negative bacteria beta-lactamase) performance is strong.This has very important meaning clinically.
Cefotetan is a kind of semi-synthetic novel cephamycin-type antibiotic of the wild mycin G of fawn that is produced by Streptomyces Oganonensis.It has the substituent cephalosporin structure of 7 α-methylamino, this structural change makes the effect of its anti-beta-lactamase strengthen, and antibacterial activity is more extensive, particularly anti-gram negative bacteria, strong than the first generation and second generation cephalosporin, and demonstrate good anti-anaerobic activity.Can resist most of beta-lactamases, as stronger than cefmetazole, cefoxitin to the antibacterial action of escherichia coli, Citrobacter, Klebsiella, husky bacterium Pseudomonas, Proteus, hemophilus influenza.Antibacterial action to gram positive bacteria such as staphylococcus, Streptococcus is more weak.To the equal stabilizer pole of various bacteriogenic beta lactamases, very strong antibacterial action is also arranged to producing the beta lactamase bacterial strain.In addition, after the cefotetan injection, have the blood drug level of higher and lasting long period and in skin, tonsil, sputum, uterus, ovary, cerebrospinal fluid, amniotic fluid, distribute, but distribution is less in milk.Cefotetan is discharged in the main urine certainly in vivo not by metabolism.Be used for shallow secondary infection, tonsillitis, respiratory system infection, empyema, biliary tract infection, peritonitis, urinary tract infection, gynecological infections etc. such as responsive microbial septicemia, burn and operative incision.
Limit or technologic difficulty owing to raw material at present, relatively weaker to the antibiotic exploitation of cephamycin-type.The Cefotetan Disodium curative effect is through clinical approval, but because Cefotetan Disodium salt is very unstable, meeting the water capacity in production, storage and use easily degrades, related substance can increase sharply, cause product defective, can not use, this gives and produces, stores and uses and all brought great difficulty.
Therefore, prior art haves much room for improvement and improves.
Summary of the invention
The objective of the invention is to,, provide a kind of Cefotetan Disodium in production, storage and use, to be difficult for degrading the pharmaceutical composition of the stable Cefotetan Disodium that is used to inject at above problems of the prior art.
The invention provides a kind of pharmaceutical composition of Cefotetan Disodium, its composition for injection for adopting freeze drying technology to make comprises Cefotetan Disodium, and wherein, described compositions also comprises adjuvant; Wherein, the mass percent of described Cefotetan Disodium is 50%～99%; The mass percent of described adjuvant is 1%～50%; Described adjuvant is the mixture of glucose and mannitol.
Compositions of the present invention, wherein, the mass percent of described Cefotetan Disodium is 60%～80%.
Compositions of the present invention, wherein, the mass percent of described adjuvant is 20%～40%.
Compositions of the present invention, wherein, the mass percent of described Cefotetan Disodium is 65%～75%.
Compositions of the present invention, wherein, the mass percent of described adjuvant is 25%～35%.
The present invention is by adding the adjuvant that can strengthen Cefotetan Disodium stability in the pharmaceutical composition of Cefotetan Disodium, suppress the rapid degraded Cefotetan Disodium is met water in production, storage and use after, improve Cefotetan Disodium stability, thereby obtained the pharmaceutical composition product of efficient, stable Cefotetan Disodium.
Below preferred embodiment of the present invention is described in detail.
In the present embodiment, the preparation technology that described pharmaceutical composition all adopts is freeze drying technology or non-freeze drying technology, specifically be meant Cefotetan Disodium is dissolved in the aqueous solution of adjuvant, add needle-use activated carbon and stir and remove by filter active carbon, aseptic filtration, lyophilizing manufactured goods in the freezer dryer are put in fill, or Cefotetan Disodium raw material and adjuvant are directly mixed packing make finished product.
In the compositions of the Cefotetan Disodium in the present embodiment, the dosage of demand when the amount of Cefotetan Disodium depends on drug use in the contained compositions accounts for 50%～99% of prescription gross weight, is preferably 60%～80%, more preferably 65%～75%.
The specific embodiment
Adjuvant in the present embodiment can in sodium benzoate, lactose, glucose, mannitol, sodium chloride, sodium bicarbonate or the sodium carbonate one or more etc.The preferred glucose that adopts is as adjuvant.Through a large amount of verification experimental verifications, glucose can significantly strengthen the stability of Cefotetan Disodium, all can obviously strengthen the stability of Cefotetan Disodium in water when mixing with above-mentioned other adjuvants when independent use glucose or with glucose, its consumption changes along with the variation of the amount of Cefotetan Disodium, general consumption is to account for 1%～50% of compositions gross weight, be preferably 20%～40%, more preferably 25%～35%.
Below provide 8 groups of specific embodiments, with the optimal component example of pharmaceutical composition that cefalexin provided by the present invention is described.In following examples, single dose comprises Cefotetan Disodium 500mg to 1000mg.
Embodiment 1:
In the present embodiment, the concrete content of each composition of the pharmaceutical composition of Cefotetan Disodium is as shown in table 1 below.
The composition component one of table 1 Cefotetan Disodium
| Component | Dosage (mg) | Account for compositions gross mass percentage ratio (%) |
| Cefotetan Disodium | 500 | 50 |
| Glucose | 500 | 50 |
According to above component, adopt freeze drying technology to make the 500mg/ bottle Cefotetan Disodium of injection.Detailed process is: Cefotetan Disodium is dissolved in the aqueous solution of glucose, adds needle-use activated carbon and stir, and remove by filter active carbon, carry out aseptic filtration again, fill places the freezer dryer lyophilizing then, makes finished product.
After the prescription dosing, cross leaching filtrate and detect related substance, the prescription that does not add glucose compares, the result shows that the related substance of the prescription dosing rear filtrate that does not add glucose is 5.4%, and the related substance that adds glucose is 3.5%, and visible glucose can significantly strengthen the stability of Cefotetan Disodium in water.
Embodiment 2:
In the present embodiment, the concrete content of each composition of the pharmaceutical composition of Cefotetan Disodium is as shown in table 2 below.
The composition component two of table 2 Cefotetan Disodium
| Component | Dosage (mg) | Account for compositions gross mass percentage ratio (%) |
| Cefotetan Disodium | 500 | 60 |
| Glucose | 333 | 40 |
According to above component, adopt freeze drying technology to make cefotetan for inj disodium 500mg/ bottle.Detailed process is: Cefotetan Disodium is dissolved in the aqueous solution of glucose, adds needle-use activated carbon and stir, and remove by filter active carbon, carry out aseptic filtration again, fill places the freezer dryer lyophilizing then, makes finished product.
After the prescription dosing, cross leaching filtrate and detect related substance, the prescription that does not add glucose compares, the result shows that the related substance of the prescription dosing rear filtrate that does not add glucose is 5.4%, and the related substance that adds glucose is 3.7%, and visible glucose can significantly strengthen the stability of Cefotetan Disodium in water.
Embodiment 3:
In the present embodiment, the concrete content of each composition of the pharmaceutical composition of Cefotetan Disodium is as shown in table 3 below.
The composition component three of table 3 Cefotetan Disodium
| Component | Dosage (mg) | Account for compositions gross mass percentage ratio (%) |
| Cefotetan Disodium | 500 | 65 |
| Glucose | 233 | 35 |
According to above component, adopt freeze drying technology to make cefotetan for inj disodium 500mg/ bottle.Detailed process is: Cefotetan Disodium is dissolved in the aqueous solution of glucose, adds needle-use activated carbon and stir, and remove by filter active carbon, carry out aseptic filtration again, fill places the freezer dryer lyophilizing then, makes finished product.
After the prescription dosing, cross leaching filtrate and detect related substance, the prescription that does not add glucose compares, the result shows that the related substance of the prescription dosing rear filtrate that does not add glucose is 5.4%, and the related substance that adds glucose is 3.2%, and visible glucose can significantly strengthen the stability of Cefotetan Disodium in water.
Embodiment 4:
In the present embodiment, the concrete content of each composition of the pharmaceutical composition of Cefotetan Disodium is as shown in table 4 below.
The composition component four of table 4 Cefotetan Disodium
| Component | Dosage (mg) | Account for compositions gross mass percentage ratio (%) |
| Cefotetan Disodium | 500 | 70.03 |
| Glucose | 143 | 20.03 |
| Mannitol | 71 | 9.94 |
According to above component, adopt freeze drying technology to make cefotetan for inj disodium 500mg/ bottle.Detailed process is: Cefotetan Disodium is dissolved in the aqueous solution of glucose and mannitol, adds needle-use activated carbon and stir, and remove by filter active carbon, carry out aseptic filtration again, fill places the freezer dryer lyophilizing then, makes finished product.
After the prescription dosing, cross leaching filtrate and detect related substance, the prescription that does not add glucose and mannitol compares, the result show do not add glucose and mannitol the related substance of prescription dosing rear filtrate be 5.4%, and the related substance that adds glucose and mannitol is 3.8%, and visible glucose and mannitol can significantly strengthen the stability of Cefotetan Disodium in water.
Embodiment 5:
In the present embodiment, the concrete content of each composition of the pharmaceutical composition of Cefotetan Disodium is as shown in table 5 below.
The composition component five of table 5 Cefotetan Disodium
| Component | Dosage (mg) | Account for compositions gross mass percentage ratio (%) |
| Cefotetan Disodium | 500 | 75 |
| Glucose | 100 | 15 |
| Lactose | 66.7 | 10 |
According to above component, adopt freeze drying technology to make cefotetan for inj disodium 500mg/ bottle.Detailed process is: Cefotetan Disodium is dissolved in the aqueous solution of glucose and lactose, adds needle-use activated carbon and stir, and remove by filter active carbon, carry out aseptic filtration again, fill places the freezer dryer lyophilizing then, makes finished product.
After the prescription dosing, cross leaching filtrate and detect related substance, the prescription that does not add glucose and lactose compares, the result shows that the related substance of the prescription dosing rear filtrate that does not add glucose and lactose is 5.4%, and the related substance that adds glucose and lactose is 3.8%, and visible glucose and lactose can significantly strengthen the stability of Cefotetan Disodium in water.
Embodiment 6:
In the present embodiment, the concrete content of each composition of the pharmaceutical composition of Cefotetan Disodium is as shown in table 6 below.
The composition component six of table 6 Cefotetan Disodium
| Component | Dosage (mg) | Account for compositions gross mass percentage ratio (%) |
| Cefotetan Disodium | 1000 | 80 |
| Glucose | 187.5 | 15 |
| Sodium chloride | 62.5 | 5 |
According to above component, adopt aseptic subpackaged technology to make cefotetan for inj disodium 1000mg/ bottle.Detailed process is: Cefotetan Disodium raw material and glucose, sodium chloride adjuvant are directly mixed packing, make finished product.
The sample dissolution that makes is detected related substance in water for injection, the prescription that does not add glucose and sodium chloride compares, the result shows that the prescription do not add glucose and sodium chloride is dissolved in that related substance is 5.7% behind the water for injection, and the related substance that adds glucose and sodium chloride is 4.0%, and visible glucose and sodium chloride can significantly strengthen the stability of Cefotetan Disodium in water.
Embodiment 7:
In the present embodiment, the concrete content of each composition of the pharmaceutical composition of Cefotetan Disodium is as shown in table 6 below.
The composition component seven of table 7 Cefotetan Disodium
| Component | Dosage (mg) | Account for compositions gross mass percentage ratio (%) |
| Cefotetan Disodium | 1000 | 90 |
| Glucose | 100 | 9 |
| Sodium bicarbonate | 11 | 1 |
According to above component, adopt aseptic subpackaged technology to make cefotetan for inj disodium 1000mg/ bottle.Detailed process is: Cefotetan Disodium raw material and glucose, sodium bicarbonate adjuvant are directly mixed packing, make finished product.
The sample dissolution that makes is detected related substance in water for injection, the prescription that does not add glucose and sodium bicarbonate compares, the result shows that the prescription do not add glucose and sodium bicarbonate is dissolved in that related substance is 5.7% behind the water for injection, and the related substance that adds glucose and sodium bicarbonate is 4.2%, and visible glucose and sodium bicarbonate can significantly strengthen the stability of Cefotetan Disodium in water.
Embodiment 8:
In the present embodiment, the concrete content of each composition of the pharmaceutical composition of Cefotetan Disodium is as shown in table 6 below.
The composition component eight of table 8 Cefotetan Disodium
| Component | Dosage (mg) | Account for compositions gross mass percentage ratio (%) |
| Cefotetan Disodium | 1000 | 99 |
| Glucose | 10.1 | 1 |
According to above component, adopt aseptic subpackaged technology to make cefotetan for inj disodium 1000mg/ bottle.Detailed process is: Cefotetan Disodium raw material and glucose adjuvant are directly mixed packing, make finished product.
The sample dissolution that makes is detected related substance in water for injection, the prescription that does not add glucose compares, the result shows that the prescription do not add glucose is dissolved in that related substance is 5.7% behind the water for injection, and the related substance that adds glucose is 4.4%, and visible glucose can significantly strengthen the stability of Cefotetan Disodium in water.
The pharmaceutical composition of the Cefotetan Disodium in the embodiment of the invention exists with the form of loose block or amorphous solid, and with the form administration that intravenous injection or quiet notes instil, single dose comprises Cefotetan Disodium 500mg to 1000mg.Adult's dosage is generally 1～2g on the one, 2 times on the one; Child dose is that every day is by body weight 40～60mg/kg, 2～3 times on the one.
In sum, the present invention is by adding the adjuvant that can strengthen Cefotetan Disodium stability in the pharmaceutical composition of Cefotetan Disodium, suppress to degrade rapidly Cefotetan Disodium is met water in production, storage and use after, improve the stability of Cefotetan Disodium, thereby obtained the pharmaceutical composition product of efficient, stable Cefotetan Disodium.
Should be appreciated that above-mentioned description at specific embodiment is comparatively detailed, can not therefore think the restriction to scope of patent protection of the present invention, scope of patent protection of the present invention should be as the criterion with claims.
Claims (5)
1. the pharmaceutical composition of a Cefotetan Disodium, its composition for injection for adopting freeze drying technology to make comprises Cefotetan Disodium, it is characterized in that described compositions also comprises adjuvant; Wherein, the mass percent of described Cefotetan Disodium is 50%～99%; The mass percent of described adjuvant is 1%～50%; Described adjuvant is the mixture of glucose and mannitol.
2. compositions as claimed in claim 1 is characterized in that, the mass percent of described adjuvant is 20%～40%.
3. compositions as claimed in claim 2 is characterized in that, the mass percent of described Cefotetan Disodium is 60%～80%.
4. compositions as claimed in claim 1 is characterized in that, the mass percent of described Cefotetan Disodium is 65%～75%.
5. compositions as claimed in claim 4 is characterized in that, the mass percent of described adjuvant is 25%～35%.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1034670A (en) * | 1988-01-18 | 1989-08-16 | 赫彻斯特股份公司 | The stable composition that cephalosporins derivatives and the common drying of a kind of stabilizing agent are made the stable method of this derivant and contain cephalosporins derivatives |
| 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 |
| CN101129381A (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 ion chelating agent |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1034670A (en) * | 1988-01-18 | 1989-08-16 | 赫彻斯特股份公司 | The stable composition that cephalosporins derivatives and the common drying of a kind of stabilizing agent are made the stable method of this derivant and contain cephalosporins derivatives |
| 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 |
| CN101129381A (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 ion chelating agent |
Non-Patent Citations (1)
| Title |
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| A. NOVELLI et al.The penetration of intramuscular cefotetan disodium into human extra-vascular fluid and maternal milk secretion.CHEMIOTERAPIA.1983,2(5),337-342. * |
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