CN105232468A - Flomoxef sodium powder injection and preparation method thereof - Google Patents
Flomoxef sodium powder injection and preparation method thereof Download PDFInfo
- Publication number
- CN105232468A CN105232468A CN201510739860.1A CN201510739860A CN105232468A CN 105232468 A CN105232468 A CN 105232468A CN 201510739860 A CN201510739860 A CN 201510739860A CN 105232468 A CN105232468 A CN 105232468A
- Authority
- CN
- China
- Prior art keywords
- sodium
- powder
- injection
- preparation
- aseptic
- 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
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides a flomoxef sodium powder injection and a preparation method thereof. The effective components in the prescription are flomoxef sodium aseptic powder and pharmaceutical adjuvants. The preparation method is as below: mixing evenly the flomoxef sodium aseptic powder and pharmaceutical adjuvants; filling the mixed powder in disinfected and sterilized control antibiotic glass bottle; and immediately plugging and sealing by an aluminum-plastic cap to obtain the flomoxef sodium powder injection. The flomoxef sodium powder injection has the advantages of good fluidity, accurate dosage, good stability, few impurity content, particle uniformity, and high solubility. The preparation method of the flomoxef sodium powder injection adopts direct fine mixing and packaging of aseptic raw materials and pharmaceutical adjuvants; the production process is simple for operation, mature in technology, easy to control, low in cost, and suitable for large-scale production and has low requirements on equipment and preparation conditions.
Description
Technical field
The invention belongs to pharmaceutical preparation, relate generally to flomocef sodium for injection powder injection formulation and preparation method.
Background technology
6315-S, have another name called (6R, 7R)-7-(2-((difluoromethyl) sulfur) acetylamino)-3-(((1-(2-ethoxy)-1H-TETRAZOLE-5-base) sulfur) methyl)-7-methoxyl group-8-oxo-5-oxa--1-azabicyclo [4.2.0] oct-2-ene-2-sodium formate, developed by Japanese Shionogi Seiyaku Kabushiki Kaisha, for white is to ivory buff powder or lyophilized products.Due to has a broad antifungal spectrum, highly stable to beta-lactamase, produce drug resistance hardly, and nephrotoxicity is very low, therefore the synthesis of 6315-S has important clinical and industrial value.
The 6315-S gone on the market at present is injection freeze-dried powder, directly prepares 6315-S by aseptic freeze-dried mode, has very high requirement for production equipment, and adopts freeze-dry process will consume huge energy consumption, adds production cost.In addition adopt 6315-S prepared by freeze-dry process, granule is uneven, includes the solids of block, thus easily causes the generation of impurity, is also unfavorable for the inspection of sample.Therefore be necessary to develop the preparation of 6315-S and preparation method to solve the problem.
Summary of the invention
In view of this, the object of the present invention is to provide a kind of flomocef sodium for injection powder injection formulation and preparation method thereof.
For realizing object of the present invention, the present invention adopts following technical scheme:
A kind of flomocef sodium for injection powder injection formulation, its prescription consists of: 6315-S aseptic powder and pharmaceutic adjuvant, pharmaceutic adjuvant comprises any one in medical sodium chloride, sodium citrate, sodium tartrate and sodium propionate, preferred medical sodium chloride, it is 70 ~ 120 μm that described 6315-S aseptic powder and the particle diameter of pharmaceutic adjuvant are, preferably 80 ~ 100 μm.
The weight ratio of described 6315-S aseptic powder and pharmaceutic adjuvant is 20:0.5 ~ 1, preferred 20:1.
Flomocef sodium for injection powder injection formulation preparation method of the present invention is: 6315-S aseptic powder and pharmaceutic adjuvant are crossed 100 mesh sieves and carries out precrushing, and recycling jet mill carries out in small, broken bits, mixes 2h after obtaining material.
The medicine bottle of flomocef sodium for injection powder injection formulation, every bottle containing main composition 6315-S 0.5g ~ 1g, preferred 1g.Every bottle containing pharmaceutic adjuvant 12 ~ 50mg, preferred 50mg.
The preparation method of flomocef sodium for injection powder injection formulation medicine bottle of the present invention is: aluminium-plastic cap is removed through outer package, dries 180 minutes, cool for subsequent use in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, cleans by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools for subsequent use.Vial is removed through outer package, is dried up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool for subsequent use by cleaning machine cleaning and clean compressed air.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, and the setting mixed powder time is 2h, for subsequent use.Pour into crossing 100 mesh sieves and jet mill 6315-S aseptic powder in small, broken bits and pharmaceutic adjuvant successively in batch mixer, cover lid, starter motor, mixed powder 2h, opens Cap for tin body and baiting valve carries out blowing.According to dosage carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.By subpackage and the intact sample of tamponade carry out rolling lid.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
As can be seen from above-mentioned technical scheme, the preparation method of flomocef sodium for injection powder injection formulation of the present invention is sterile raw material and pharmaceutic adjuvant directly accurate mixed powder, subpackage, simple in production process operation, technology maturation, easily controls, to equipment and preparation condition less demanding, cost is low, is suitable for large-scale production.Flomoxef sodium powder-needle preparation good fluidity of the present invention, dosage are accurately, good stability, impurity content are few, uniform particles, dissolubility are high.
Detailed description of the invention
The invention will be further described by way of example more below, provides implementation detail of the present invention, but be not be intended to limit protection scope of the present invention.
Embodiment 1
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool for subsequent use in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, cleans by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools for subsequent use.Vial is removed through outer package, is dried up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool for subsequent use by cleaning machine cleaning and clean compressed air.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, and the setting mixed powder time is 2h, for subsequent use.By cross 100 mesh sieves and jet mill in small, broken bits 6315-S aseptic powder 5000g and medical sodium chloride 250g pour into successively in batch mixer, cover lid, starter motor, mixed powder 2h, opens Cap for tin body and baiting valve carries out blowing.Contain the standard of main composition 6315-S 1g and medical sodium chloride 50mg by every 1 bottle, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.By subpackage and the intact sample of tamponade carry out rolling lid.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 2
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool for subsequent use in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, cleans by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools for subsequent use.Vial is removed through outer package, is dried up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool for subsequent use by cleaning machine cleaning and clean compressed air.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, and the setting mixed powder time is 2h, for subsequent use.To cross 100 mesh sieves and jet mill 6315-S aseptic powder 5000g in small, broken bits and medical sodium chloride 250g pours in batch mixer successively, cover lid, starter motor, mixed powder 2h, opens Cap for tin body and baiting valve carries out blowing.Contain the standard of main composition 6315-S 0.5g and medical sodium chloride 25mg by every 1 bottle, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.By subpackage and the intact sample of tamponade carry out rolling lid.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 3
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool for subsequent use in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, cleans by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools for subsequent use.Vial is removed through outer package, is dried up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool for subsequent use by cleaning machine cleaning and clean compressed air.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, and the setting mixed powder time is 2h, for subsequent use.To cross 100 mesh sieves and jet mill 6315-S aseptic powder 4000g in small, broken bits and medical sodium chloride 100g pours in batch mixer successively, cover lid, starter motor, mixed powder 2h, opens Cap for tin body and baiting valve carries out blowing.Contain the standard of main composition 6315-S 1g and medical sodium chloride 25mg by every 1 bottle, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.By subpackage and the intact sample of tamponade carry out rolling lid.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 4
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool for subsequent use in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, cleans by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools for subsequent use.Vial is removed through outer package, is dried up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool for subsequent use by cleaning machine cleaning and clean compressed air.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, and the setting mixed powder time is 2h, for subsequent use.To cross 100 mesh sieves and jet mill 6315-S aseptic powder 5000g in small, broken bits and medical sodium citrate 250g pours in batch mixer successively, cover lid, starter motor, mixed powder 2h, opens Cap for tin body and baiting valve carries out blowing.Contain the standard of main composition 6315-S 1g and the medical sodium citrate 50mg of adjuvant by every 1 bottle, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.By subpackage and the intact sample of tamponade carry out rolling lid.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 5
Preparation method:
Aluminium-plastic cap is removed through outer package, dries 180 minutes, cool for subsequent use in 120 DEG C of baking ovens.Rubber cork is removed through outer package equally, cleans by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools for subsequent use.Vial is removed through outer package, is dried up, eventually pass 350 DEG C of dry heat sterilizations 10 minutes, cool for subsequent use by cleaning machine cleaning and clean compressed air.Cleaning batch mixer tank body and baiting valve, regulate intervalometer, and the setting mixed powder time is 2h, for subsequent use.To cross 100 mesh sieves and jet mill 6315-S aseptic powder 5000g in small, broken bits and medical sodium tartrate 250g pours in batch mixer successively, cover lid, starter motor, mixed powder 2h, opens Cap for tin body and baiting valve carries out blowing.Contain the standard of main composition 6315-S 1g and the medical sodium tartrate 50mg of adjuvant by every 1 bottle, carry out aseptic subpackaged with control antibiotic glass bottle, tamponade.By subpackage and the intact sample of tamponade carry out rolling lid.Carry out lamp inspection by rolling the intact sample of lid, label and pack.
Embodiment 6
According to method continuous seepage three batches of flomocef sodium for injection powder injection formulations respectively of embodiment 1 ?5, carry out particle diameter, content, purity, pH value and water solublity to products obtained therefrom and measure, measurement result is in table 1.
The particle diameter of the different flomoxef sodium injection of table 1, content, purity, pH value and water solublity measurement result
From table 1 result, flomoxef sodium powder-needle preparation dosage of the present invention accurately, good stability, impurity content are few, uniform particles, dissolubility are high.
Embodiment 7
By the operation standard of long-term experiment and Acceleration study, detecting above group is first the stability of flomoxef sodium injection of embodiment 1 ?5, and does control experiment with the flomoxef preparation of sodium of listing.Wherein 6315-S and related impurities content adopt high performance liquid chromatography (HPLC) to detect.Concrete testing conditions is as follows:
Pillar: YMC-C18 liquid-phase chromatographic column, internal diameter 4.6mm, length 15cm, particle diameter 5 μm.Column temperature: 25 DEG C.Determined wavelength: 246nm.Mobile phase: add water 1000 milliliters, dissolves 6.94g potassium dihydrogen phosphate, 3.22g sodium hydrogen phosphate dodecahydrate and 1.60g bromination tetra-n-butyl ammonium successively.Get more than 750 milliliters solution, and add in this solution in 250 ml methanol, be made into mobile phase.
The long-term experiment result of the different flomoxef sodium injection of table 2
Table 3 goes on the market the long-term experiment result of flomoxef preparation of sodium
The Acceleration study result of the different flomoxef sodium injection of table 4
Table 5 goes on the market the Acceleration study result of flomoxef preparation of sodium
Show according to the long-term experiment of above flomoxef sodium injection of the present invention and listing flomoxef preparation of sodium and Acceleration study result, flomoxef sodium injection provided by the invention has higher purity and better stability than the flomoxef preparation of sodium of listing, and flomoxef sodium injection quality safety of the present invention is stablized in storage process, can long term storage.
Embodiment 8
Detecting above group is first the dissolution velocity of flomoxef sodium injection of embodiment 1 ?5, and does control experiment with the flomoxef preparation of sodium of listing.
Table 6 dissolution velocity comparative experiments result
| Numbering | Dissolution velocity |
| Embodiment 1 first | 15s |
| Embodiment 2 first | 15s |
| Embodiment 3 first | 17s |
| Embodiment 4 first | 21s |
| Embodiment 5 first | 30s |
| Listing flomoxef preparation of sodium | 37s |
From table 6 result, flomoxef sodium powder-needle preparation dissolution velocity of the present invention significantly improves.
Embodiment 9
Adopting doubling dilution to detect above group is respectively first the minimum inhibitory concentration MIC of flomoxef sodium injection of embodiment 1-5
90, and do control experiment with the flomoxef preparation of sodium of listing.
Table 7 minimum inhibitory concentration MIC
90test experience result
From table 7 result, compare with listing flomoxef preparation of sodium, flomoxef sodium powder-needle preparation of the present invention has significant therapeutic effect for bacterial infection.
After the explanation of reading this method, those skilled in the art can make various change or amendment to the present invention, and these equivalent form of values fall within the application's appended claims institute limited range equally.
Claims (10)
1. a flomocef sodium for injection powder injection formulation, it is characterized in that: be made up of 6315-S aseptic powder and pharmaceutic adjuvant, pharmaceutic adjuvant comprises any one in medical sodium chloride, sodium citrate, sodium tartrate and sodium propionate, and described 6315-S aseptic powder and the particle diameter of pharmaceutic adjuvant are 70 ~ 120 μm.
2. flomocef sodium for injection preparation according to claim 1, is characterized in that: described pharmaceutic adjuvant is medical sodium chloride.
3. flomocef sodium for injection preparation according to claim 1 and 2, is characterized in that: the weight ratio of described 6315-S aseptic powder and pharmaceutic adjuvant is 20:0.5 ~ 1.
4. flomocef sodium for injection preparation according to claim 3, is characterized in that: the particle diameter of 6315-S aseptic powder and pharmaceutic adjuvant is 80 ~ 100 μm, and the weight ratio of 6315-S aseptic powder and pharmaceutic adjuvant is 20:1.
5. claim 1 ?the preparation method of 4 arbitrary described flomocef sodium for injection powder injection formulations be: 6315-S aseptic powder and pharmaceutic adjuvant are crossed 100 mesh sieves and carries out precrushing, recycling jet mill carries out in small, broken bits, mixes 2h after obtaining material.
6. claim 1 ?the medicine bottle of 4 arbitrary described flomocef sodium for injection powder injection formulations, it is characterized in that: every bottle containing main composition 6315-S 0.5g ~ 1g, pharmaceutic adjuvant 12 ~ 50mg.。
7. the medicine bottle of flomocef sodium for injection powder injection formulation according to claim 6, is characterized in that: every bottle containing main composition 6315-S 1g, pharmaceutic adjuvant 50mg.
8. the preparation method of the medicine bottle of the flomocef sodium for injection powder injection formulation described in claim 6 or 7, is characterized in that, comprise the steps:
1) preparation vessels and batch mixer is cleared up;
2) pour into crossing 100 mesh sieves and jet mill 6315-S aseptic powder in small, broken bits and pharmaceutic adjuvant successively in batch mixer, mixed powder 2h;
3) aseptic subpackaged.
9. the preparation method of flomocef sodium for injection powder injection formulation according to claim 8, is characterized in that, described step 1) cleaning preparation vessels and batch mixer comprise:
Plastic-aluminum is placed in 120 DEG C of baking ovens and dries 180 minutes, cools for subsequent use;
Rubber cork cleans by washing plug machine, in 150 DEG C of dry heat sterilizations 180 minutes, cools for subsequent use;
Vial is dried up by cleaning machine cleaning and clean compressed air, eventually passes 350 DEG C of dry heat sterilizations 10 minutes, cools for subsequent use;
Cleaning batch mixer tank body and baiting valve, regulate intervalometer, and the setting mixed powder time is 2h, for subsequent use.
10. the preparation method of flomocef sodium for injection powder injection formulation according to claim 8, is characterized in that, described step 3) aseptic subpackagedly to comprise:
Open Cap for tin body after mixed powder completes and baiting valve carries out blowing, according to dosage carry out aseptic subpackaged with control antibiotic glass bottle, tamponade; By subpackage and the intact sample of tamponade carry out rolling lid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510739860.1A CN105232468A (en) | 2015-11-03 | 2015-11-03 | Flomoxef sodium powder injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510739860.1A CN105232468A (en) | 2015-11-03 | 2015-11-03 | Flomoxef sodium powder injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105232468A true CN105232468A (en) | 2016-01-13 |
Family
ID=55030474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510739860.1A Pending CN105232468A (en) | 2015-11-03 | 2015-11-03 | Flomoxef sodium powder injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105232468A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101966152A (en) * | 2010-10-29 | 2011-02-09 | 广州白云山天心制药股份有限公司 | Cefpiramide composite |
| CN103142617A (en) * | 2013-03-29 | 2013-06-12 | 山东罗欣药业股份有限公司 | Cefuroxime lysine medicinal composition |
| CN103536550A (en) * | 2013-10-15 | 2014-01-29 | 海南卫康制药(潜山)有限公司 | Flomoxef sodium composition freeze-dried powder for injection |
-
2015
- 2015-11-03 CN CN201510739860.1A patent/CN105232468A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101966152A (en) * | 2010-10-29 | 2011-02-09 | 广州白云山天心制药股份有限公司 | Cefpiramide composite |
| CN103142617A (en) * | 2013-03-29 | 2013-06-12 | 山东罗欣药业股份有限公司 | Cefuroxime lysine medicinal composition |
| CN103536550A (en) * | 2013-10-15 | 2014-01-29 | 海南卫康制药(潜山)有限公司 | Flomoxef sodium composition freeze-dried powder for injection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103693791A (en) | Sterile injection water production technique and sterile compressed air preparation method | |
| CN102659818A (en) | Hydrochloric acid cefotiam crystalline compound, preparation method thereof and medicine combination containing compound | |
| CN102526040B (en) | Method for preparing composition of mezlocillin sodium and sulbactam sodium for injection in ratio of 4: 1 | |
| CN106606494A (en) | Pimavanserin pharmaceutical composition and preparation method thereof | |
| CN103435496A (en) | Bromhexine hydrochloride compound, and preparation method, medicinal composition and preparation thereof | |
| CN104840427B (en) | A kind of pharmaceutical composition containing Menglusitena | |
| CN105232468A (en) | Flomoxef sodium powder injection and preparation method thereof | |
| CN103224504B (en) | Injection sodium cefonicid compound, preparation method and pharmaceutical composition | |
| CN104688743B (en) | Cefprozil suspension and preparation method thereof | |
| CN104224725A (en) | Tebipenem pivoxil granule and preparation method thereof | |
| CN105456213A (en) | Montelukast sodium tablet | |
| CN105250241A (en) | Transdermal patch preparation process | |
| CN105963321B (en) | A kind of composite vitamin E medicine membrane of oral cavity and preparation method thereof | |
| CN103191061B (en) | Cefbuperazone sodium composition powder for injection and preparation method thereof | |
| CN105085511B (en) | A kind of new aztreonam compound | |
| CN103655578A (en) | Powder mixing method for cefoperazone sodium and sulbactam sodium | |
| CN104188914B (en) | Amoxicillin powder and its production technology | |
| CN105055169B (en) | A method of preparing Imipenem and Cilasatin Sodium aseptic powdery | |
| CN103536578B (en) | A kind of Cefixime Capsules and preparation method thereof | |
| CN104208031B (en) | A kind of Olanzapine Tablets composition and preparation method thereof | |
| CN101002767A (en) | Dispersion tablets of penicillin V potassium, and its preparing method | |
| CN110051637A (en) | Amoxicillin and clavulanate potassium preparation and preparation method thereof | |
| CN103040758B (en) | A kind of pharmaceutical composition containing cefathiamidine compound and preparation method thereof | |
| CN104940162A (en) | Cefixime capsules and preparation method thereof | |
| CN103284961B (en) | Preparing method of cobamamide freeze-drying formulation for injection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160113 |