CN1261439C - Cefixime sodium pharmaceutical composition and its preparation and application - Google Patents
Cefixime sodium pharmaceutical composition and its preparation and application Download PDFInfo
- Publication number
- CN1261439C CN1261439C CN 200410040017 CN200410040017A CN1261439C CN 1261439 C CN1261439 C CN 1261439C CN 200410040017 CN200410040017 CN 200410040017 CN 200410040017 A CN200410040017 A CN 200410040017A CN 1261439 C CN1261439 C CN 1261439C
- Authority
- CN
- China
- Prior art keywords
- application
- cefixime
- cefixime micronized
- sodium
- medical compounds
- Prior art date
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- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 title claims abstract description 45
- 229960002129 cefixime Drugs 0.000 title claims abstract description 45
- 239000011734 sodium Substances 0.000 title claims abstract description 29
- 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 title claims abstract description 27
- 229910052708 sodium Inorganic materials 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 238000002347 injection Methods 0.000 claims abstract description 18
- 239000007924 injection Substances 0.000 claims abstract description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 12
- 239000000843 powder Substances 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 230000003115 biocidal effect Effects 0.000 claims description 4
- 238000001291 vacuum drying Methods 0.000 claims description 4
- 229930186147 Cephalosporin Natural products 0.000 claims description 3
- 229940124587 cephalosporin Drugs 0.000 claims description 3
- 150000001780 cephalosporins Chemical class 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 238000000967 suction filtration Methods 0.000 claims description 3
- 239000006186 oral dosage form Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 7
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 229940088710 antibiotic agent Drugs 0.000 abstract description 2
- 239000002552 dosage form Substances 0.000 abstract 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 150000001782 cephems Chemical class 0.000 abstract 1
- 239000012530 fluid Substances 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 241000894006 Bacteria Species 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 4
- 241000193998 Streptococcus pneumoniae Species 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 229940124588 oral cephalosporin Drugs 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000606768 Haemophilus influenzae Species 0.000 description 2
- 241000588655 Moraxella catarrhalis Species 0.000 description 2
- 241000588653 Neisseria Species 0.000 description 2
- 241000588770 Proteus mirabilis Species 0.000 description 2
- 241000589516 Pseudomonas Species 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 241000304886 Bacilli Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 241000588923 Citrobacter Species 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 241000193985 Streptococcus agalactiae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention discloses a medicament compound of cefixime sodium, of which the molecular formula is C16H13N5Na2O7S2 and molecular mass is 497.5. The medicament compound is prepared by the following steps: 1 mol of cefixime and 2 mol of sodium bicarbonate are added with ethanol to be crystallized after completely reacting with each other at the normal temperature and pressure, and a crystallized product is filtered in a suction way, recrystallized, and dried in vacuum at a temperature below 60 DEG C to obtain the compound. The medicament compound not only can be used for peroral dosage forms but also can be used for various dosage forms, containing fluid injection, powder injection, freeze-dried powder injection, and the like in the application as cephem antibiotics. The medicament compound has the advantages of convenient and simple synthesis, low cost, less pollution, good water solubility, good absorbability and high therapeutic effect.
Description
Technical field:
The present invention relates to nitrogenous and heterogeneous ring compound sulphur, especially relate to Cefixime Micronized sodium medical compounds.The present invention also relates to the preparation method and the application of this medical compounds simultaneously.
Background technology:
Microbiotic Cefixime Micronized (Cefixime, C
16H
15N
5O
7S
2) be third generation oral cephalosporin antibiotics.Cefixime Micronized has broad-spectrum antibacterial action to gram-positive microorganism and negative bacterium, particularly the hemophilus influenzae in the influenza Pseudomonas in the gram-positive microorganism (as: streptococcus pneumoniae, epidermis suis), streptococcus pneumoniae and the Gram-negative bacteria, Morakot Bordetella, catarrh Pseudomonas, proteus mirabilis, gonococcus, branhamella catarrhalis, intestinal bacteria, Klebsiella, serratia, proteus, stream bacillus etc. is demonstrated the germicidal action stronger than other oral cephalosporanic olefinic.It has characteristics such as wide spectrum, efficient, anti-enzyme, low toxicity, is the anti-infective oral pharmaceutical of widespread use clinically.
And Cefixime Micronized is as oral cephalosporin, and it is the medicine of using dosage minimum in the cephalosporin antibiotic of all clinical uses up to now, and persistent effective bacteriocidal concentration is arranged in vivo.The formulation of listing is tablet, capsule, granule at present, but because this medicine solubleness in water is little, causes the bioavailability of these oral preparations low; The Cefixime Micronized poorly water-soluble can only be brought into play its anti-microbial effect as oral cephalosporin.Therefore, the use range of Cefixime Micronized has been subjected to certain limitation, especially just can't use concerning those can't swallow and exist the patient of dysphgia at all.
Summary of the invention:
The problem that the present invention is intended to solve the Cefixime Micronized poorly water-soluble, can't be prepared into injection provides a kind of Cefixime Micronized sodium medical compounds and preparation method thereof and as antibiotic application.This medical compounds good water solubility, synthetic easy, cost is low, has the curative effect same with Cefixime Micronized, can remedy the defective that Cefixime Micronized can't be prepared into injection, thereby has enlarged the use range of Cefixime Micronized effectively.
For achieving the above object, the technical solution used in the present invention is as follows:
A kind of Cefixime Micronized sodium medical compounds is characterized in that its molecular formula is C with following structural formula (I) expression
16H
13N
5Na
2O
7S
2, molecular weight is 497.5.
A kind of preparation method of Cefixime Micronized sodium medical compounds, it is characterized in that: at normal temperatures and pressures, after the sodium bicarbonate complete reaction with 1 mole Cefixime Micronized and 2 moles, add alcohol crystal, recrystallization again behind the suction filtration promptly gets Cefixime Micronized sodium product in vacuum-drying below 60 ℃.
Reaction formula of the present invention is as follows:
This product is white, off-white color or light yellow crystalline powder, and is soluble in water, slightly is dissolved in alcohol, is insoluble to acetone, and pH is 6～8.
A kind of Cefixime Micronized sodium medical compounds is as the application of cephalosporin antibiotic.
Described Cefixime Micronized sodium also can be used for multiple formulations such as liquid drugs injection, powder pin, freeze-dried powder except that can be used for oral dosage form.
The present invention is synthetic easy, cost is low, pollution is few, and good water solubility can be made into multiple formulations such as powder pin, liquid drugs injection, freeze-dried powder, and good absorption, the curative effect height.
Embodiment:
Embodiment 1: the preparation of Cefixime Micronized sodium
At normal temperatures and pressures, the sodium bicarbonate aqueous solution with 507.5 gram Cefixime Micronizeds and 1680 grams 10% adds in the reaction flask stirring reaction 2 hours, adding 10 gram needle-use activated carbons, stirred 20 minutes, and filtered, filtrate adds alcohol crystal, suction filtration, 50 ℃ of vacuum-dryings get Cefixime Micronized sodium first product.Under aseptic condition, use the aqueous ethanolic solution recrystallization, 50 ℃ of vacuum-dryings promptly get Cefixime Micronized sodium finished product 427 grams.
Yield: 85.9%
Proterties: off-white color crystalline powder
Content: 99.1%
PH:7.2 (10% aqueous solution)
Embodiment 2: the preparation of injection Cefixime Micronized sodium injection
The Cefixime Micronized sodium raw materials is pressed the packing of sterile powder injection prepared, promptly get injection Cefixime Micronized sodium injection.
Embodiment 3: the preparation of injection Cefixime Micronized sodium freeze-dried powder injection
Prescription Cefixime Micronized sodium 500 grams
5% sodium hydrogen carbonate solution is an amount of
Water for injection adds to 1000 milliliters
Method for making places sterile chamber at indoor Cefixime Micronized sodium 500 grams that take by weighing of aseptic technique, adds sterilized water for injection to about 500 milliliters, stirring makes molten, adds 5% sodium hydrogen carbonate solution and regulates in PH to 6.8～7.2 scopes, adds water for injection to capacity, the needle-use activated carbon that adds amount of preparation 2% then, stirred filter just, smart filter 5～10 minutes, packing, about pre-freeze 2 hours, lid was jumped a queue, rolled to frozen drying promptly after 24 hours.
Embodiment 4: pharmacology and toxicological experiment are relatively
Experimental drug: the Cefixime Micronized sodium of injection is as trial-product, with Cefixime Micronized raw material and preparation thereof in contrast.
(1) effect experiment:
Antibacterial tests result shows: the Cefixime Micronized sodium of injection to intestinal bacilli such as intestinal bacteria, pneumobacillus, Proteus mirabilis, bacterium vulgare and citrobacter etc.＜1mg/L; To MIC≤1mg/L of hemophilus influenzae, to the MIC≤0.5mg/L of gonococcus and branhamella catarrhalis; To MIC＜0.5mg/L streptococcus agalactiae, micrococcus scarlatinae, to MIC≤1mg/L of streptococcus pneumoniae; Most streptococcic MIC＜0.5mg/L.
Compare with the oral solid formulation of Cefixime Micronized, Cefixime Micronized sodium does not have the low problem of bioavailability, and its antimicrobial spectrum and antibacterial ability are identical with Cefixime Micronized, has characteristics such as wide spectrum, efficient, anti-enzyme, low toxicity.
(2) acute toxicity test
Cefixime Micronized mouse administration LD
50＞10000mg/Kg (oral); 4420～5840mg/Kg (quiet notes).Rat administration LD
5＞10000mg/Kg (oral); 6990～7890mg/Kg (quiet notes).The LD of Cefixime Micronized sodium injected in mice administration
50Be 5425mg/Kg, the 95% credible 5153.8～5296.2mg/Kg that is limited to illustrates that the toxicity of Cefixime Micronized sodium is little.
(3) part toxicity test
The Cefixime Micronized sodium of injection does not have blood vessel irritation, can not cause allergy and haemolysis.
Claims (5)
1, a kind of Cefixime Micronized sodium medical compounds is characterized in that its molecular formula is C with following structural formula (I) expression
16H
13N
5Na
2O
7S
2, molecular weight is 497.5,
2, the preparation method of medical compounds as claimed in claim 1, it is characterized in that: at normal temperatures and pressures, after the sodium bicarbonate complete reaction with 1 mole Cefixime Micronized and 2 moles, add alcohol crystal, recrystallization again behind the suction filtration promptly gets Cefixime Micronized sodium product in vacuum-drying below 60 ℃.
3, the application of medical compounds as claimed in claim 1 is characterized in that as the application in preparation cephalosporin antibiotic medicine.
4, the application of medical compounds as claimed in claim 3 is characterized in that being used for the application of liquid drugs injection, powder pin, freeze-dried powder formulation.
5, the application of medical compounds as claimed in claim 3 is characterized in that being used for the application of oral dosage form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410040017 CN1261439C (en) | 2004-06-18 | 2004-06-18 | Cefixime sodium pharmaceutical composition and its preparation and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410040017 CN1261439C (en) | 2004-06-18 | 2004-06-18 | Cefixime sodium pharmaceutical composition and its preparation and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1594322A CN1594322A (en) | 2005-03-16 |
| CN1261439C true CN1261439C (en) | 2006-06-28 |
Family
ID=34664431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410040017 Expired - Fee Related CN1261439C (en) | 2004-06-18 | 2004-06-18 | Cefixime sodium pharmaceutical composition and its preparation and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1261439C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100417383C (en) * | 2006-03-07 | 2008-09-10 | 中国药科大学 | A kind of effervescent tablet containing cefixime and its preparation method |
| CN102198104A (en) * | 2011-05-16 | 2011-09-28 | 王万玉 | Cefixime freeze-dried powder injection and preparation method thereof |
| CN104004003B (en) * | 2013-02-22 | 2016-05-25 | 广州白云山医药集团股份有限公司白云山制药总厂 | Cefixime derivative and its production and use |
-
2004
- 2004-06-18 CN CN 200410040017 patent/CN1261439C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1594322A (en) | 2005-03-16 |
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| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Sichuan Chuantou Medicine Biotechnology Co., Ltd. Assignor: Yu Anguo Contract fulfillment period: 2006.7.2 to 2011.7.2 contract change Contract record no.: 2009510000029 Denomination of invention: Cefixime sodium pharmaceutical composition and its preparation and application Granted publication date: 20060628 License type: Exclusive license Record date: 2009.9.11 |
|
| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2006.7.2 TO 2011.7.2; CHANGE OF CONTRACT Name of requester: SICHUAN CHUANTOU MEDICINE BIOTECHNOLOGY LIMITED LI Effective date: 20090911 |
|
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20060628 Termination date: 20130618 |