CN103371968A - Tobramycin sulfate injection and process for preparing same - Google Patents
Tobramycin sulfate injection and process for preparing same Download PDFInfo
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- CN103371968A CN103371968A CN 201210111796 CN201210111796A CN103371968A CN 103371968 A CN103371968 A CN 103371968A CN 201210111796 CN201210111796 CN 201210111796 CN 201210111796 A CN201210111796 A CN 201210111796A CN 103371968 A CN103371968 A CN 103371968A
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Abstract
The invention provides a tobramycin sulfate injection and a process for preparing the tobramycin sulfate injection. Every 10,000ml of the tobramycin sulfate injection contains the following raw materials: 400g of tobramycin, 25-38g of sodium bisulfite, 0.8-1.2g of EDTA-2Na (ethylenediaminetetraacetic acid and disodium) and the balance of water for injection. The process comprises the following steps of: adding the water for injection into a proportioning tank, wherein the amount of the added water for injection is 80% of total amount of the raw materials; introducing CO2 into the water for injection for 10-20 minutes until the water for injection is saturated; adding tobramycin into the proportioning tank; adding 25% (volume concentration) sulfuric acid into the proportioning tank; stirring to dissolve the tobramycin; adding the sodium bisulfite and solution of the EDTA-2Na dissolved with the water for injection into the proportioning tank; keeping the pH value of a solution at 4.7-5.1; adding the water for injection until the total amount of the solution reaches the preparation amount; stirring the solution uniformly; introducing CO2 into the solution; filtering the solution with a folded filtering element until the solution is clear; filling the solution into an ampoule, and sealing the ampoule, wherein N2 is introduced into the ampoule in the process of filling the solution. The steps are carried out in the aseptic preoaration condition. The process provided by the invention has the advantage that the SAL (sterility assurance level) of the sterilized tobramycin sulfate injection can be not more than 10<-3>.
Description
Technical field
The present invention relates to medical technical field, relate in particular to tobramycin sulfate injection and preparation process thereof.
Background technology
The tobramycin sulfate injection belongs to aminoglycoside antibiotics, and Main Ingredients and Appearance is tobramycin.This product belongs to aminoglycoside antibiotics.Antimicrobial spectrum and gentamycin are approximate, and the gram-negative bacterias such as escherichia coli, aerobacteria, klebsiella bacillus, proteus mirabilis, the positive Bacillus proteus of some indole, Pseudomonas aeruginosa, some Neisseria, some non-pigment serratia marcecens and shigella dysenteriae are had antibacterial action; This product is strong 3～5 times than gentamycin to the antibacterial action of Pseudomonas aeruginosa, and is extremely sensitive to this product to the Pseudomonas aeruginosa of gentamycin medium sensitivity.In the gram positive bacteria, staphylococcus aureus (comprise and produce the lactamase strain) is responsive to this product; Streptococcus (comprising micrococcus scarlatinae, streptococcus pneumoniae, streptococcus faecalis etc.) is all to this product drug resistance.Anaerobe (Bacteroides), tubercule bacillus, rickettsia, virus and fungus are also to this product drug resistance.The mechanism of action of this product is to be combined with bacterial ribosome 30S subunit, anti-bacteria protein synthetic.
This product mainly is applicable to Neonatal Sepsis, septicemia, central nervous system infection (comprising meningitis), urogenital infections, pulmonary infection, biliary tract infection, abdominal cavity infection and peritonitis, bone infection, burn, the skin soft-tissue infection due to Pseudomonas aeruginosa, Proteus, escherichia coli, Klebsiella, Enterobacter, the Serratia, acute and chronic otitis media, sinusitis etc., or unites for staphy lococcus infection (the methicillin-resistant bacterial strain is invalid) with other antibacterials.But sheath inner injecting medicine-feeding when this product is used for Pseudomonas aeruginosa meningitis or ventriculitis; Can be with the molten suction this product of seasonal epidemic pathogens as auxiliary treatment when being used for bronchus and pulmonary infection.It is invalid that this product infects most D group B streptococcus.
State Food and Drug Administration evaluates the center and has issued [2008] No. 7 literary compositions of state's food medicine prison notes--" about the notice of issue chemical drugs injection and the requirement of multicomponent Biochemical Drugs injection basic fundamental " (being designated hereinafter simply as " notice ") in 2008, its literary composition regulation: small-volume injection should be taked terminal sterilization technique, the suggestion first-selection is excessively killed method (F0 〉=12), can not tolerate the condition of excessively killing such as product, can consider to adopt probability of surviving method (8≤F0＜12), but all should guarantee the horizontal sterility assurance of the SAL(sterilization assurance level after the product sterilization) be not more than 10
-6Adopt other F0 value less than the technique of 8 terminal sterilization condition, will not approve in principle.Can not adopt terminal sterilization technique if any sufficient according to proof, and be the kind of clinical necessary drug administration by injection, can consider to adopt sterile production technique, but should guarantee that SAL is not more than 10
-3Adopted simultaneously the auxiliary kind of sterilizing of flowing steam for filtration sterilization technique, proposed amendments is terminal sterilization technique, to really adopting the kind of terminal sterilization technique, should be revised as sterile production technique.
At present, 100 ℃ of existing sterilization process of 30 minutes of tobramycin sulfate injection can't satisfy above-mentioned " notice " for the requirement of the SAL after the product sterilization, investigate it through test and can not adopt terminal sterilization technique, therefore need to improve existing preparation process.
Summary of the invention
Main purpose of the present invention is to provide a kind of tobramycin sulfate injection and preparation process thereof, solves problems of the prior art and deficiency.
For achieving the above object, technical scheme provided by the invention is:
A kind of tobramycin sulfate injection in every 10000ml injection, comprises following raw material:
Tobramycin 400g
Sodium sulfite 25g ~ 38g
EDTA-2Na 0.8g~1.2g
Water for injection adds to 10000ml.
A kind of tobramycin sulfate injection in every 10000ml injection, comprises following raw material:
Tobramycin 400g
Sodium sulfite 32g
EDTA-2Na 1g
Water for injection adds to 10000ml.
The preparation process of arbitrary described tobramycin sulfate injection in above-mentioned two kinds of prescriptions has following steps:
(1) in material-compound tank, add the water for injection below 30 ℃ of preparing total amount 80%, and the logical CO of Xiang Shuizhong
2Gas 10 ~ 20 minutes is until saturated;
(2) tobramycin is added in the material-compound tank;
(3) again with the 25%(volumetric concentration) sulphuric acid adds in the material-compound tank, and stir and made the tobramycin dissolving in 5 minutes;
(4) add in the material-compound tank with sodium sulfite and with the water-soluble EDTA-2Na solution of 30 ~ 80ml injection;
(5) whether the pH value of test solution is 4.7 ~ 5.1, if pH value in this interval, then directly enters next step; If pH value not in this interval, then adds an amount of 25%(volumetric concentration in addition) sulphuric acid or 20%(mass concentration) NaOH regulates pH value, until this value is 4.7 ~ 5.1;
(6) add the water for injection below 30 ℃ until the solution total amount is the preparation total amount, with solution stirring 5 ~ 15 minutes until evenly, pass into simultaneously CO
2
(7) successively be filtered to clear and bright by 0.45 μ m and the collapsible filter element of crossing of 0.22 μ m solution;
(8) solution that step (7) is obtained carries out embedding, logical N in ampoule during embedding
2
Further, all carry out under the sterile production condition described step (1) ~ (8).
Further, further comprise afterwards sterilization steps (9) in step (8), described step (9) is the product sterilization that step (8) is obtained, sterilising conditions be 100 ℃ 30 minutes.
In sum, beneficial effect of the present invention is: guaranteed the horizontal sterility assurance of SAL(sterilization assurance level in the tobramycin sulfate injection after the sterilization) be not more than 10
-3
The specific embodiment
Below in conjunction with embodiment the present invention is described in detail, embodiment is intended to explain and non-limiting technical scheme of the present invention.
The object of the invention is to, a kind of tobramycin sulfate injection and preparation process thereof are provided.
Embodiment 1:
A kind of tobramycin sulfate injection in the described injection of every 10000ml, comprises following raw material:
Tobramycin 400g
Sodium sulfite 25g
EDTA-2Na 0.8g
Water for injection adds to 10000ml.
A kind of preparation process of tobramycin sulfate injection has following steps:
(1) in material-compound tank, add the water for injection below 30 ℃ of preparing total amount 80%, and the logical CO of Xiang Shuizhong
2Gas 10 ~ 20 minutes is until saturated;
(2) tobramycin is added in the material-compound tank;
(3) again with the 25%(volumetric concentration) sulphuric acid adds in the material-compound tank, and stir and made the tobramycin dissolving in 5 minutes;
(4) add in the material-compound tank with sodium sulfite and with the water-soluble EDTA-2Na solution of 30 ~ 80ml injection;
(5) whether the pH value of test solution is 4.7 ~ 5.1, if pH value in this interval, then directly enters next step; If pH value not in this interval, then adds an amount of 25%(volumetric concentration in addition) sulphuric acid or 20%(mass concentration) NaOH regulates pH value, until this value is 4.7 ~ 5.1;
(6) add water for injection below 30 ℃ until the solution total amount is 10000ml, with solution stirring 5 ~ 15 minutes until evenly, pass into simultaneously CO
2
(7) successively be filtered to clear and bright by 0.45 μ m and the collapsible filter element of crossing of 0.22 μ m solution;
(8) solution that step (7) is obtained carries out embedding, logical N in ampoule during embedding
2
All carry out under the sterile production condition above-mentioned steps (1) ~ (8).
Embodiment 2:
A kind of tobramycin sulfate injection in the described injection of every 10000ml, comprises following raw material:
Tobramycin 400g
Sodium sulfite 38g
EDTA-2Na 1.2g
Water for injection adds to 10000ml.
A kind of preparation process of tobramycin sulfate injection has following steps:
(1) in material-compound tank, add the water for injection below 30 ℃ of preparing total amount 80%, and the logical CO of Xiang Shuizhong
2Gas 10 ~ 20 minutes is until saturated;
(2) tobramycin is added in the material-compound tank;
(3) again with the 25%(volumetric concentration) sulphuric acid adds in the material-compound tank, and stir and made the tobramycin dissolving in 5 minutes;
(4) add in the material-compound tank with sodium sulfite and with the water-soluble EDTA-2Na solution of 30 ~ 80ml injection;
(5) whether the pH value of test solution is 4.7 ~ 5.1, if pH value in this interval, then directly enters next step; If pH value not in this interval, then adds an amount of 25%(volumetric concentration in addition) sulphuric acid or 20%(mass concentration) NaOH regulates pH value, until this value is 4.7 ~ 5.1;
(6) add water for injection below 30 ℃ until the solution total amount is 10000ml, with solution stirring 5 ~ 15 minutes until evenly, pass into simultaneously CO
2
(7) successively be filtered to clear and bright by 0.45 μ m and the collapsible filter element of crossing of 0.22 μ m solution;
(8) solution that step (7) is obtained carries out embedding, logical N in ampoule during embedding
2
(9) the product sterilization that step (8) is obtained, sterilising conditions be 100 ℃ 30 minutes.
Embodiment 3:
A kind of tobramycin sulfate injection in the described injection of every 10000ml, comprises following raw material:
Tobramycin 400g
Sodium sulfite 32g
EDTA-2Na 1g
Water for injection adds to 10000ml.
A kind of preparation process of tobramycin sulfate injection has following steps:
(1) in material-compound tank, add the water for injection below 30 ℃ of preparing total amount 80%, and the logical CO of Xiang Shuizhong
2Gas 10 ~ 20 minutes is until saturated;
(2) tobramycin is added in the material-compound tank;
(3) again with the 25%(volumetric concentration) sulphuric acid adds in the material-compound tank, and stir and made the tobramycin dissolving in 5 minutes;
(4) add in the material-compound tank with sodium sulfite and with the water-soluble EDTA-2Na solution of 30 ~ 80ml injection;
(5) whether the pH value of test solution is 4.7 ~ 5.1, if pH value in this interval, then directly enters next step; If pH value not in this interval, then adds an amount of 25%(volumetric concentration in addition) sulphuric acid or 20%(mass concentration) NaOH regulates pH value, until this value is 4.7 ~ 5.1;
(6) add water for injection below 30 ℃ until the solution total amount is 10000ml, with solution stirring 5 ~ 15 minutes until evenly, pass into simultaneously CO
2
(7) successively be filtered to clear and bright by 0.45 μ m and the collapsible filter element of crossing of 0.22 μ m solution;
(8) solution that step (7) is obtained carries out embedding, logical N in ampoule during embedding
2
All carry out under the sterile production condition above-mentioned steps (1) ~ (8).
Embodiment 4:
A kind of tobramycin sulfate injection in the described injection of every 10000ml, comprises following raw material:
Tobramycin 400g
Sodium sulfite 35g
EDTA-2Na 1.1g
Water for injection adds to 10000ml.
A kind of preparation process of tobramycin sulfate injection has following steps:
(1) in material-compound tank, add the water for injection below 30 ℃ of preparing total amount 80%, and the logical CO of Xiang Shuizhong
2Gas 10 ~ 20 minutes is until saturated;
(2) tobramycin is added in the material-compound tank;
(3) again with the 25%(volumetric concentration) sulphuric acid adds in the material-compound tank, and stir and made the tobramycin dissolving in 5 minutes;
(4) add in the material-compound tank with sodium sulfite and with the water-soluble EDTA-2Na solution of 30 ~ 80ml injection;
(5) whether the pH value of test solution is 4.7 ~ 5.1, if pH value in this interval, then directly enters next step; If pH value not in this interval, then adds an amount of 25%(volumetric concentration in addition) sulphuric acid or 20%(mass concentration) NaOH regulates pH value, until this value is 4.7 ~ 5.1;
(6) add water for injection below 30 ℃ until the solution total amount is 10000ml, with solution stirring 5 ~ 15 minutes until evenly, pass into simultaneously CO
2
(7) successively be filtered to clear and bright by 0.45 μ m and the collapsible filter element of crossing of 0.22 μ m solution;
(8) solution that step (7) is obtained carries out embedding, logical N in ampoule during embedding
2
(9) the product sterilization that step (8) is obtained, sterilising conditions be 100 ℃ 30 minutes.
The above only is preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (5)
1. the tobramycin sulfate injection is characterized in that, in the described injection of every 10000ml, comprises following raw material:
Tobramycin 400g
Sodium sulfite 25g ~ 38g
EDTA-2Na 0.8g~1.2g
Water for injection adds to 10000ml.
2. tobramycin sulfate injection according to claim 1 is characterized in that, in the described injection of every 10000ml, comprises following raw material:
Tobramycin 400g
Sodium sulfite 32g
EDTA-2Na 1g
Water for injection adds to 10000ml.
3. the preparation process of arbitrary described tobramycin sulfate injection in the claim 1 ~ 2 is characterized in that having following steps:
(1) in material-compound tank, add the water for injection below 30 ℃ of preparing total amount 80%, and the logical CO of Xiang Shuizhong
2Gas 10 ~ 20 minutes is until saturated;
(2) tobramycin is added in the material-compound tank;
(3) again with the 25%(volumetric concentration) sulphuric acid adds in the material-compound tank, and stir and made the tobramycin dissolving in 5 minutes;
(4) add in the material-compound tank with sodium sulfite and with the water-soluble EDTA-2Na solution of 30 ~ 80ml injection;
(5) whether the pH value of test solution is 4.7 ~ 5.1, if pH value in this interval, then directly enters next step; If pH value not in this interval, then adds an amount of 25%(volumetric concentration in addition) sulphuric acid or 20%(mass concentration) NaOH regulates pH value, until this value is 4.7 ~ 5.1;
(6) add the water for injection below 30 ℃ until the solution total amount is the preparation total amount, with solution stirring 5 ~ 15 minutes until evenly, pass into simultaneously CO
2
(7) successively be filtered to clear and bright by 0.45 μ m and the collapsible filter element of crossing of 0.22 μ m solution;
(8) solution that step (7) is obtained carries out embedding, logical N in ampoule during embedding
2
4. preparation process as claimed in claim 3 is characterized in that, all carry out under the sterile production condition described step (1) ~ (8).
5. preparation process as claimed in claim 3 is characterized in that, further comprises afterwards sterilization steps in step (8)
(9), described step (9) is the product sterilization that step (8) is obtained, sterilising conditions be 100 ℃ 30 minutes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210111796 CN103371968A (en) | 2012-04-17 | 2012-04-17 | Tobramycin sulfate injection and process for preparing same |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210111796 CN103371968A (en) | 2012-04-17 | 2012-04-17 | Tobramycin sulfate injection and process for preparing same |
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| CN103371968A true CN103371968A (en) | 2013-10-30 |
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|---|---|---|---|
| CN 201210111796 Pending CN103371968A (en) | 2012-04-17 | 2012-04-17 | Tobramycin sulfate injection and process for preparing same |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106265606A (en) * | 2015-05-13 | 2017-01-04 | 上海禾丰制药有限公司 | A kind of tobramycin sulfate inhalation solution and preparation method thereof |
| CN106389312A (en) * | 2016-09-18 | 2017-02-15 | 天津金耀药业有限公司 | Pharmaceutical composition of metaraminol bitartrate injection |
| CN114796107A (en) * | 2022-05-09 | 2022-07-29 | 西藏邦臣药业集团有限公司 | Tobramycin sulfate injection containing nicotinide diphosphate and preparation method thereof |
-
2012
- 2012-04-17 CN CN 201210111796 patent/CN103371968A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106265606A (en) * | 2015-05-13 | 2017-01-04 | 上海禾丰制药有限公司 | A kind of tobramycin sulfate inhalation solution and preparation method thereof |
| CN106389312A (en) * | 2016-09-18 | 2017-02-15 | 天津金耀药业有限公司 | Pharmaceutical composition of metaraminol bitartrate injection |
| CN114796107A (en) * | 2022-05-09 | 2022-07-29 | 西藏邦臣药业集团有限公司 | Tobramycin sulfate injection containing nicotinide diphosphate and preparation method thereof |
| CN114796107B (en) * | 2022-05-09 | 2024-01-09 | 西藏邦臣药业集团有限公司 | Tobramycin sulfate injection containing nicotin diphosphate and preparation method thereof |
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Application publication date: 20131030 |