CN101697961A - New cefmenoxime hydrochloride preparation for drug administration by injection and preparation method thereof - Google Patents
New cefmenoxime hydrochloride preparation for drug administration by injection and preparation method thereof Download PDFInfo
- Publication number
- CN101697961A CN101697961A CN200910208262A CN200910208262A CN101697961A CN 101697961 A CN101697961 A CN 101697961A CN 200910208262 A CN200910208262 A CN 200910208262A CN 200910208262 A CN200910208262 A CN 200910208262A CN 101697961 A CN101697961 A CN 101697961A
- Authority
- CN
- China
- Prior art keywords
- cefmenoxime hydrochloride
- sodium bicarbonate
- abbott
- cefmenoxime
- injection
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a new cefmenoxime hydrochloride preparation which is prepared by mixing cefmenoxime hydrochloride asepsis powder with cosolvent sodium bicarbonate asepsis powder, wherein the weight ratio of cefmenoxime hydrochloride (reduced to be pure cefmenoxime hydrochloride) to sodium bicarbonate is 1:0.1-1:0.3, preferably is 1:0.2 i.e. 0.1-0.3g of sodium bicarbonate asepsis powder is added into 1g of cefmenoxime hydrochloride (reduced to be pure cefmenoxime hydrochloride). After evenly mixed, asepsis split charging technology is adopted, and mixture is added into an aseptic soda-lime glass moulding injection bottle according to the labelled amount, the plug is pressed, a cover is rolled, full inspection is carried out, and the qualified product is packaged to obtain the cefmenoxime hydrochloride for injection. The product can overcome the problems of poor cefmenoxime hydrochloride dissolubility, poor stability, high impurity of relevant substance, polymer and the like, low content and the like of the existing cefmenoxime hydrochloride for injection and can better ensure clinic drug using safety. The invention belongs to the technical field of drug.
Description
Technical field
The present invention relates to a kind of Abbott 50192 novel formulation, particularly relate to Abbott 50192 novel formulation of the injectable administration that contains the cosolvent sodium bicarbonate and preparation method thereof.Belong to medical technical field.
Background technology
Abbott 50192, chemical name: (6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyimino acetylamino]-3-[[[1-methyl isophthalic acid H-tetrazolium-5-yl]-sulfur] methyl]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-formates hydrochlorate (2: 1).
Chemical structural formula:
Abbott 50192 is the third generation cephalosporin of Japanese Takede Chemical Industries Ltd exploitation, and Gram-negative and male aerobe and anaerobe are all had antibacterial action, and the same with other third generation cephalosporin have an extremely strong antibacterial activity.In the gram negative bacteria, antibacterial action to escherichia coli, pneumobacillus is stronger slightly than cefotiam, obviously be better than the cefazolin sodium of the first generation, the antibacterial action of influenza being bitten blood bacillus, Bacillus proteus, serratia marcesens, Citrobacter, Enterobacter is also more intense, and Bacteroides is also had very strong antibacterial action.In gram positive bacteria, also stronger to micrococcus scarlatinae, pneumococcal antibacterial action.Peptococcus, Peptostreptococcus also there are the strong antibiotic effect, stable to beta-lactamase.This product is since nineteen eighty-three listing, and clinical practice constantly enlarges, and sales volume rises year by year, and enters state's latest edition pharmacopeia such as Japan and the United States.
Pharmacological action: this product is the semisynthetic cephalosporins broad ectrum antibiotic of the third generation, reaches bactericidal action by the biosynthesis that suppresses bacteria cell wall.It is because it has the good cell outer membrane permeability that this product has strong antibacterial action to gram negative bacteria, stable to beta-lactamase, and the affinity to penicillin-binding protein (PBPs) 1A, 1B and 3 is strong, thereby pair cell wall mucopeptide is cross-linked to form and has stronger inhibition.
In vitro tests shows that this product all has effect to gram positive bacteria and negative bacterium.To the antimicrbial power of gram positive bacteria, with micrococcus scarlatinae and streptococcus pneumoniae and opinion, effect is better than cephalo for amine (CTM) and cefazolin sodium (CEZ).Peptococcus, Peptostreptococcus are shown strong antimicrbial power.To the antimicrbial power of gram negative bacteria, with escherichia coli and pneumobacillus and opinion is better than CTM slightly, far be better than CEZ.To hemophilus influenza, Proteus, emplastic serratia, citrobacter belongs to, the antimicrbial power of intestinal Pseudomonas is stronger than CTM, and is strong more than CEZ.In addition Bacteroides is also shown strong antimicrbial power.
At present, the cefmenoxime hydrochloride in product of Ying Yonging is the mixed powder of Abbott 50192 and natrium carbonicum calcinatum clinically, during use this product is dissolved in 0.9% sodium chloride injection or the glucose injection intravenous drip.
There is following aspect problem in this preparation:
1, because Abbott 50192 is insoluble in water, therefore, under the hydrotropy condition, could dissolve.Natrium carbonicum calcinatum can at first form hydrate on the surface in course of dissolution, cause the sodium carbonate course of dissolution slow, thereby influenced the dissolving of Abbott 50192, makes product poorly soluble, and dissolution time is long, has brought inconvenience for clinical use.
2, because sodium carbonate alkalescence is strong, in course of dissolution, make the local alkaline higher phenomenon that occurs to make product in course of dissolution, produce a large amount of impurity, brought risk to clinical application.
3, process is quickened and long-time stability investigation test discovery the cefmenoxime hydrochloride in product of listing, and product stability is poor, and color is obviously deepened in storage process, and related substance and polymer obviously increase, and content obviously descends.
4, because the cefmenoxime hydrochloride in product of listing is poorly soluble, dissolution time is long during clinical use, inconvenient operation, and in long course of dissolution, impurity obviously increases, and makes adverse reaction rate height in the clinical practice, has increased the risk of clinical application.
Summary of the invention
The novel formulation that the purpose of this invention is to provide problems such as a kind ofly overcoming that existing cefmenoxime hydrochloride in is poorly soluble, impurity height such as poor stability, related substance and polymer, content are low, can improve the dissolubility of product, and help to improve the quality of products and product stability, better guarantee clinical drug safety.
Since sodium bicarbonate alkalescence than sodium carbonate a little less than, course of dissolution relaxes, be easy to Abbott 50192 in the combination of salt acid molecule, make the product course of dissolution even and rapid, and the pH value amplitude of variation is little in course of dissolution, impurity produces few, has improved security of products, has reduced the clinical application risk.
Therefore, cefmenoxime hydrochloride in novel formulation of the present invention is the mixed powder preparation of Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder, has promptly guaranteed the quality and the product stability of product in production and storage, use, has made things convenient for clinical practice again.
Technical scheme:
The Abbott 50192 aseptic powder is mixed with cosolvent sodium bicarbonate aseptic powder, Abbott 50192 (pure) is 1: 0.1～1: 0.3 with the weight ratio of sodium bicarbonate, and preferred proportion is 1: 0.2, and promptly 1g Abbott 50192 (pure) aseptic powder adds the sodium bicarbonate aseptic powder of 0.1～0.3g, behind the mix homogeneously, adopt aseptic subpackaged technology, be loaded in the cillin bottle after the sterilization tamponade by labelled amount, roll lid, full inspection, qualified back packing promptly obtains this product---cefmenoxime hydrochloride in.
The specific embodiment
Embodiment 1
The prescription of cefmenoxime hydrochloride in:
Abbott 50192 1000g (pure)
Sodium bicarbonate 200g
??????????????????????????????????????
Make 1000
Preparation technology:
Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the accurate weighing of recipe quantity, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, full inspection, qualified back packing.
Test example 1 cefmenoxime hydrochloride in stability test
Product in 25 ℃ of placements, is carried out 24 months long-term stable experiment, investigate its stability, the result shows, this preparation stabilization.The results are shown in Table 1.
Table 1
The room temperature stability test of test example 2 cefmenoxime hydrochloride in 0.9% sodium chloride injection
With draw 0.9% sodium chloride injection 10ml dissolving of this product 1, solution is preserved down in room temperature (25 ℃), investigates its stability, and the result shows, and is stable in the solution at room temperature 2 hours.The results are shown in Table 2.
Table 2
| Time | Color | Clarity | PH value | Content % | Total impurities % | Polymer % |
| 0 hour | ＜yellow No. 2 | Clarification | ??6.9 | ??95.8 | ??0.9 | ??0.2 |
| 1 hour | ＜yellow No. 3 | Clarification | ??7.0 | ??94.9 | ??1.0 | ??0.3 |
| 2 hours | ＜yellow No. 4 | Clarification | ??7.0 | ??94.2 | ??1.3 | ??0.5 |
| 4 hours | ＜yellow No. 5 | Clarification | ??7.1 | ??93.3 | ??1.6 | ??0.6 |
Test example 3 cefmenoxime hydrochloride in safety testings
Test by " chemicals zest, anaphylaxis and hemolytic investigative technique guideline " with this product:
(1) 0.5ml/ sensitization of normal saline solution (15mg/ml) of intramuscular injection cefmenoxime hydrochloride in the next day that Cavia porcellus being distinguished every, totally 3 times, normal saline solution (30mg/ml) 1ml of every single dose intravenous injection cefmenoxime hydrochloride in of the 14th and 21 day difference attacks after the sensitization first, after the attack, symptoms of allergic such as perpendicular hair, dyspnea, sneeze, death do not appear in Cavia porcellus.
(2) cefmenoxime hydrochloride in (200mg/ml) when clinical maximum administration concentration does not have haemolysis and agglutination to rabbit erythrocyte.
(3) the normal saline diluent (75mg/ml, 2ml/kg, 1 time/day) of continuous 5 days slow injection injection usefulness Abbott 50192s of rabbit auricular vein, perusal blood vessel no abnormality seen changes; The result of histopathologic examination shows, administration pick up the ears edge vein blood vessel and surrounding tissue and control sides comparison no significant difference.
The result shows that the administration of this product rabbit auricular vein does not have the obvious stimulation effect to rabbit blood vessel and muscle; Intravenous administration does not have sensitization to Cavia porcellus; Tame rabbit erythrocyte is not had external haemolysis and causes agglutination, illustrated that this product is safe and reliable, meet the injection requirement.
Embodiment 2
The prescription of cefmenoxime hydrochloride in:
Abbott 50192 1000g (pure)
Sodium bicarbonate 100g
???????????????????????????????????
Make 1000
Preparation technology:
Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the accurate weighing of recipe quantity, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, full inspection, qualified back packing.
Check result sees Table 3.
Table 3
| Project | Color | Clarity | PH value | Content % | Total impurities % |
| The result | ＜yellow No. 2 | Clarification | ??5.0 | ??95.2 | ??0.8 |
Embodiment 3
The prescription of cefmenoxime hydrochloride in:
Abbott 50192 1000g (pure)
Sodium bicarbonate 300g
???????????????????????????????????????
Make 1000
Preparation technology:
Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the accurate weighing of recipe quantity, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, full inspection, qualified back packing.
Check result sees Table 4.
Table 4
| Project | Color | Clarity | PH value | Content % | Total impurities % |
| The result | ＜yellow No. 5 | Clarification | ??8.3 | ??94.2 | ??1.8 |
Embodiment 4
The prescription of cefmenoxime hydrochloride in:
Abbott 50192 1000g (pure)
Sodium bicarbonate 130g
????????????????????????????????????
Make 1000
Preparation technology:
Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the accurate weighing of recipe quantity, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, full inspection, qualified back packing.
Check result sees Table 5.
Table 5
| Project | Color | Clarity | PH value | Content % | Total impurities % |
| The result | ＜yellow No. 1 | Clarification | ??5.6 | ??95.0 | ??0.9 |
Embodiment 5
The prescription of cefmenoxime hydrochloride in:
Abbott 50192 1000g (pure)
Sodium bicarbonate 150g
???????????????????????????
Make 1000
Preparation technology:
Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the accurate weighing of recipe quantity, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, full inspection, qualified back packing.
Check result sees Table 6.
Table 6
| Project | Color | Clarity | PH value | Content % | Total impurities % |
| The result | ＜yellow No. 3 | Clarification | ??6.1 | ??95.1 | ??0.8 |
Embodiment 6
The prescription of cefmenoxime hydrochloride in:
Abbott 50192 1000g (pure)
Sodium bicarbonate 180g
???????????????????????????????????
Make 1000
Preparation technology:
Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the accurate weighing of recipe quantity, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, full inspection, qualified back packing.
Check result sees Table 7.
Table 7
| Project | Color | Clarity | PH value | Content % | Total impurities % |
| The result | ＜yellow No. 3 | Clarification | ??6.4 | ??94.9 | ??0.9 |
Embodiment 7
The prescription of cefmenoxime hydrochloride in:
Abbott 50192 1000g (pure)
Sodium bicarbonate 210g
????????????????????????????????????????
Make 1000
Preparation technology:
Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the accurate weighing of recipe quantity, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, full inspection, qualified back packing.
Check result sees Table 8.
Table 8
| Project | Color | Clarity | PH value | Content % | Total impurities % |
| The result | ＜yellow 3 | Clarification | ??6.9 | ??95.0 | ??0.9 |
Embodiment 8
The prescription of cefmenoxime hydrochloride in:
Abbott 50192 1000g (pure)
Sodium bicarbonate 220g
?????????????????????????????????????????
Make 1000
Preparation technology:
Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the accurate weighing of recipe quantity, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, full inspection, qualified back packing.
Check result sees Table 9.
Table 9
| Project | Color | Clarity | PH value | Content % | Total impurities % |
| The result | ＜yellow No. 3 | Clarification | ??7.3 | ??94.3 | ??1.2 |
Embodiment 9
The prescription of cefmenoxime hydrochloride in:
Abbott 50192 1000g (pure)
Sodium bicarbonate 250g
?????????????????????????????????????????
Make 1000
Preparation technology:
Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the accurate weighing of recipe quantity, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, full inspection, qualified back packing.
Check result sees Table 10.
Table 10
| Project | Color | Clarity | PH value | Content % | Total impurities % |
| The result | ＜yellow No. 3 | Clarification | ??7.8 | ??93.2 | ??1.6 |
Claims (4)
1. the Abbott 50192 novel formulation of an injectable administration contains active ingredient Abbott 50192 and cosolvent carbonate.
2. novel formulation as claimed in claim 1 is characterized in that cosolvent is a sterile sodium bicarbonate.
3. novel formulation as claimed in claim 1 is characterized in that the active ingredient hydrochloric acid cefmenoxime (pure) and the weight ratio of sodium bicarbonate are 1: 0.1～1: 0.3, and preferred proportion is 1: 0.2.
4. as the preparation method of claim 1 and 3 described novel formulation, it is the sodium bicarbonate aseptic powder that 1g Abbott 50192 (pure) aseptic powder adds 0.1～0.3g, behind the mix homogeneously, adopt aseptic subpackaged technology, be sub-packed in the cillin bottle after the sterilization tamponade by labelled amount, roll lid, full inspection, qualified back packing promptly obtains this product---cefmenoxime hydrochloride in.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910208262A CN101697961A (en) | 2009-10-24 | 2009-10-24 | New cefmenoxime hydrochloride preparation for drug administration by injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910208262A CN101697961A (en) | 2009-10-24 | 2009-10-24 | New cefmenoxime hydrochloride preparation for drug administration by injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101697961A true CN101697961A (en) | 2010-04-28 |
Family
ID=42146426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910208262A Pending CN101697961A (en) | 2009-10-24 | 2009-10-24 | New cefmenoxime hydrochloride preparation for drug administration by injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101697961A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102499922A (en) * | 2011-10-20 | 2012-06-20 | 桂林澳林制药有限责任公司 | Cefmenoxime hydrochloride composition for injection and preparation thereof |
| CN104906035A (en) * | 2015-05-28 | 2015-09-16 | 浙江长典医药有限公司 | Cefmenoxime hydrochloride and low-sodium carrier drug composition for children |
-
2009
- 2009-10-24 CN CN200910208262A patent/CN101697961A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102499922A (en) * | 2011-10-20 | 2012-06-20 | 桂林澳林制药有限责任公司 | Cefmenoxime hydrochloride composition for injection and preparation thereof |
| CN102499922B (en) * | 2011-10-20 | 2012-11-21 | 桂林澳林制药有限责任公司 | Cefmenoxime hydrochloride composition for injection and preparation thereof |
| CN104906035A (en) * | 2015-05-28 | 2015-09-16 | 浙江长典医药有限公司 | Cefmenoxime hydrochloride and low-sodium carrier drug composition for children |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2713989A1 (en) | Stable liquid formulations of anti-infective agents and adjusted anti-infective agent dosing regimens | |
| CN101574351A (en) | Cefmetazole preparation used for injection and preparation method thereof | |
| CN100536843C (en) | Pharmaceutical composition for injection containing faropenem | |
| CN101697961A (en) | New cefmenoxime hydrochloride preparation for drug administration by injection and preparation method thereof | |
| CN102552275B (en) | Injection powder and injection preparation of cefoperazone sodium-tazobactam combination | |
| CN102860980A (en) | Method for preparing rocuronium bromide injection | |
| CN101904822B (en) | Faropenem sodium freeze-drying powder and preparation method thereof | |
| CN103073562A (en) | Method for refining cefamandole nafate, cefamandole nafate and application thereof | |
| CN102727451B (en) | Cefmetazole-containing pharmaceutical composition | |
| CN103083322B (en) | Medicinal composition containing injection cefmenoxime hydrochloride and compound amino acid injection | |
| CN103059045B (en) | Novel amoxicillin sodium and clavulanate potassium compound and pharmaceutical composition thereof | |
| CN102716096B (en) | Medicinal composition containing cefotiam hydrochloride | |
| CN102716075B (en) | Ceftizoxime sodium-containing pharmaceutical composition | |
| CN106176722A (en) | A kind of imipenem for injection cilastatin sodium aseptic powdery preparation and preparation method thereof | |
| CN103655460B (en) | Injection medicinal composition containing aztreonam, as well as preparation method and application thereof | |
| CN101972257B (en) | A kind of pharmaceutical composition containing Moxifloxacin | |
| CN105476954A (en) | Lomefloxacin hydrochloride injection and preparation method thereof | |
| CN107875154B (en) | Composition containing piperacillin, pharmaceutical preparation and application thereof | |
| CN105534961A (en) | Tobramycin inhalation solution and preparing method | |
| CN100516071C (en) | Amino butanetriol salt of cephalosporin compounds and preparing method | |
| CN106902116B (en) | Application of rifamycin-quinolizidone dual-target molecule | |
| CN101744825A (en) | Cefmenoxime hydrochloride preparation and preparation method | |
| CN105012249A (en) | Injection rifampicin and preparing method thereof | |
| CN102824310A (en) | Cefotiam-hydrochloride-containing medicine preparation and preparation method thereof | |
| CN116763783A (en) | Cloxacillin sodium composition and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20100428 |