CN102451154A - Netilmicin sulfate injection and preparation method thereof - Google Patents
Netilmicin sulfate injection and preparation method thereof Download PDFInfo
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- CN102451154A CN102451154A CN2010105209373A CN201010520937A CN102451154A CN 102451154 A CN102451154 A CN 102451154A CN 2010105209373 A CN2010105209373 A CN 2010105209373A CN 201010520937 A CN201010520937 A CN 201010520937A CN 102451154 A CN102451154 A CN 102451154A
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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Abstract
The invention relates to a netilmicin sulfate injection and a preparation method thereof. The netilmicin sulfate injection is characterized in that: every 1,000 ml of injection contains 50,000,000 units of netilmicin sulfate, 0.5-2g of an antioxidant and 0.1-1g of a complexing agent, and the pH value of the netilmicin sulfate injection is 5.3-5.7. A preparation process of the netilmicin sulfate injection comprises the following steps of: cooling an appropriate amount of water for injection to below 30 DEG C under the condition that the air cleanliness is in a hundred level; introducing nitrogen to remove oxygen; adding a prescription dose of the antioxidant and the complexing agent into the water for injection for completely dissolving; adding a prescription dose of the netilmicin sulfate into a solution; stirring for completely dissolving; adsorbing with 0.05-0.2 percent (g/ml) needle active carbon; primarily filtering with one set of 1mum filter for removing carbon; adjusting the pH to 5.3-5.7 with a sodium citrate solution; stirring uniformly; fixing the volume to a full dose by using the water for injection; finely filtering with one set of 0.22/0.22mum polypropylene foldable filter core filter and two sets of 0.22/0.22mum polyether sulfone microporous membrane filter core filters for removing bacteria; embedding under a hundred-level condition (introducing nitrogen in the entire process); assisting in sterilizing at the temperature of 100 DEG C; and performing lamp inspection and packaging. Due to the adoption of a scientific formula and process, the stability of the netilmicin sulfate injection is ensured; and due to the adoption of a sterile assistant sterilization preparation method, the sterile guarantee level of a medicament is raised.
Description
Technical field:
The present invention relates to medical technical field, a kind of semisynthetic aminoglycoside broad ectrum antibiotic netilmicin sulfate inj and preparation method thereof.
Background technology:
The mechanism of action of netilmicin sulfate inj is to combine with bacterial ribosome 30S subunit, suppresses the synthetic of bacterioprotein.Be applicable to severe infections due to the responsive gram negative bacilli of treatment, like neonate sepsis, septicemia, central nervous system infection (comprising meningitis), urinary tract genital system infection, respiratory tract infection, gastrointestinal infection, peritonitis, biliary tract infection, skin or bone infection due to Pseudomonas aeruginosa, Proteus (indole is positive and negative), escherichia coli, Klebsiella, Enterobacter, Serratia and the citrobacter genus etc., otitis media, sinusitis, soft tissue infection, listeriosis etc.These article often can obtain synergism with beta-lactam class drug combination.
A lot of cephalosporins and quinolones new drug though go on the market in recent years, but still can't the unique aminoglycoside medicaments of metalepsis mechanism.Netilmicin sulfate is that such medicine nephrotoxicity is slight and more rare, and ototoxicity is low than gentamycin, tobramycin and amikacin, and clinical efficacy is superior to gentamycin etc.Become and treat the choice drug that responsive gram negative bacilli comprises severe infections due to the bacillus pyocyaneus clinically because of it has more safety and effectiveness.
Netilmicin sulfate is soluble in water, in the netilmicin structure unsaturated double-bond is arranged, and injection is easy oxidation discoloration in production and storage process.At present this kind listing preparation has small-volume injection, lyophilized injectable powder, bulk capacity injection, but produce and storage process in phenomenons such as in various degree oxidation stain, related substance rising are all arranged.According to experimental result and relevant bibliographical information, the principal element that influences its injection quality is: the pH value of sterilising temp, airborne oxygen, medicinal liquid, and its sterilising temp is difficult above 105 ℃, otherwise content descends, its colour changed into yellow, and related substance obviously raises.This just means that the injection of this product is difficult for adopting the terminal sterilization method to produce.So there is dosage form at present: small-volume injection, the conventional production method (100 ℃ of sterilizations) of bulk capacity injection can not fully guarantee aseptic requirement, and especially the bulk capacity injection risk is bigger; Lyophilized injectable powder is though aseptic assurance can reach 10
-3Level, but exist complicated process of preparation, cost higher, clinical use such as need redissolve at shortcoming.Therefore, improve stability of drug, invention is a kind of can effectively prevent the netilmicin sulfate oxidation stain and make the method for preparing of its aseptic assurance higher level to be very useful.
Summary of the invention:
The objective of the invention is to the defective to prior art, provide that a kind of technology is simple relatively, steady quality, aseptic assurance level are higher, the netilmicin sulfate inj of drug safety and preparation method thereof.
Technical scheme of the present invention is achieved in that sulfur acid netilmicin 5,000 ten thousand units in per 1000 milliliters of injection, antioxidant 0.5～2g, and chelating agent 0.1～1g, pH value is between 5.3～5.7.Preparation technology of the present invention is: at air purity is under hundred grades of conditions, will prepare in right amount with water for injection to be cooled to below 30 ℃, logical nitrogen deoxygenation; The antioxidant of recipe quantity, chelating agent added make dissolving fully in the water for injection, the netilmicin sulfate of recipe quantity is added in the above-mentioned solution, stir and make dissolving fully; With the needle-use activated carbon absorption of 0.05～0.2% (g/ml) concentration, take off charcoal with the filter just of 1 μ m filter, 1 cover, regulate pH between 5.3～5.7 with liquor sodii citratis; Stir; Be settled to full dose with water for injection, with 0.22/0.22 μ m polypropylene foldable filter element filter 1 cover and the 2 cover fine straining degerming of 0.22/0.22 μ m microporous membrane of polyethersulfone candle filter, embedding under hundred grades of conditions (overall process inflated with nitrogen); Auxiliary sterilization below 100 ℃, lamp inspection, packing promptly get.
Technical essential of the present invention is: be that the exposed operation of medicinal liquid adopts sterile production technology from being formulated into filling and sealing 1; 2, preparation is cooled to below 30 ℃ and towards the nitrogen deoxygenation with water for injection; 3, selected suitable antioxidant and chelating agent for use; 4, the pH value of making the pH value regulator with liquor sodii citratis and controlling medicinal liquid is between 5.3～5.7; 5, ultrafiltration combines with aseptic filtration; 6, auxiliary sterilization below 100 ℃.The prescription of science and technology have guaranteed the stability of netilmicin sulfate inj, and is aseptic+auxiliary method for preparing of sterilizing, and improved the aseptic assurance level of medicine.
The specific embodiment:
Embodiment 1: at air purity is under hundred grades of conditions, gets 700ml water for injection, is cooled to about 30 ℃, logical N
210 minutes, adding sodium sulfite 1g, calcium disodium edetate 0.1g stirred and make dissolving fully, and the netilmicin sulfate that adds 5,000 ten thousand units stirs and makes dissolving fully; Needle-use activated carbon with 0.1% (g/ml) concentration adsorbed 15 minutes; Take off charcoal with the filter just of 1 μ m filter, 1 cover, add water for injection, regulate pH between 5.3～5.7 with 10% liquor sodii citratis to nearly 1000ml; Stir; Add water for injection to 1000ml, with 0.22/0.22 μ m polypropylene foldable filter element filter 1 cover and the 2 cover fine straining degerming of 0.22/0.22 μ m microporous membrane of polyethersulfone candle filter, embedding under hundred grades of conditions (overall process inflated with nitrogen); 100 ℃ of auxiliary sterilizations in 2,30 minutes, lamp inspection, packing promptly get.
Embodiment 2: at air purity is under hundred grades of conditions, gets 700ml water for injection, is cooled to about 30 ℃, logical N
210 minutes, adding sodium pyrosulfite 1g, disodium edetate 0.1g stirred and make dissolving fully, and the netilmicin sulfate that adds 5,000 ten thousand units stirs and makes dissolving fully; Needle-use activated carbon with 0.1% (g/ml) concentration adsorbed 15 minutes; Take off charcoal with the filter just of 1 μ m filter, 1 cover, add water for injection, regulate pH between 5.3～5.7 with 10% liquor sodii citratis to nearly 1000ml; Stir; Add water for injection to 1000ml, with 0.22/0.22 μ m polypropylene foldable filter element filter 1 cover and the 2 cover fine straining degerming of 0.22/0.22 μ m microporous membrane of polyethersulfone candle filter, embedding under hundred grades of conditions (overall process inflated with nitrogen); Auxiliary sterilization in 100 ℃, 30 minutes, lamp inspection, packing promptly get.
Embodiment 3: at air purity is under hundred grades of conditions, gets 700ml water for injection, is cooled to about 30 ℃, logical N
210 minutes, adding sodium sulfite 1g, disodium edetate 0.1g stirred and make dissolving fully, and the netilmicin sulfate that adds 5,000 ten thousand units stirs and makes dissolving fully; Needle-use activated carbon with 0.1% (g/ml) concentration adsorbed 15 minutes; Take off charcoal with the filter just of 1 μ m filter, 1 cover, add water for injection, regulate pH between 5.3～5.7 with 10% liquor sodii citratis to nearly 1000ml; Stir; Add water for injection to 1000ml, with 0.22/0.22 μ m polypropylene foldable filter element filter 1 cover and the 2 cover fine straining degerming of 0.22/0.22 μ m microporous membrane of polyethersulfone candle filter, embedding under hundred grades of conditions (overall process inflated with nitrogen); Auxiliary sterilization in 100 ℃, 30 minutes, lamp inspection, packing promptly get.
Embodiment 4: at air purity is under hundred grades of conditions, gets 700ml water for injection, is cooled to about 30 ℃, logical N
210 minutes, adding sodium pyrosulfite 1g, calcium disodium edetate 0.1g stirred and make dissolving fully, and the netilmicin sulfate that adds 5,000 ten thousand units stirs and makes dissolving fully; Needle-use activated carbon with 0.1% (g/ml) concentration adsorbed 15 minutes; Take off charcoal with the filter just of 1 μ m filter, 1 cover, add water for injection, regulate pH between 5.3～5.7 with 10% liquor sodii citratis to nearly 1000ml; Stir; Add water for injection to 1000ml, with 0.22/0.22 μ m polypropylene foldable filter element filter 1 cover and the 2 cover fine straining degerming of 0.22/0.22 μ m microporous membrane of polyethersulfone candle filter, embedding under hundred grades of conditions (overall process inflated with nitrogen); Auxiliary sterilization in 100 ℃, 30 minutes, lamp inspection, packing promptly get.
Claims (7)
1. netilmicin sulfate inj and preparation method thereof is characterized in that: sulfur acid netilmicin 5,000 ten thousand units in per 1000 milliliters of injection, and antioxidant 0.5～2g, chelating agent 0.1～1g, pH value is between 5.3～5.7.
2. the method for preparing of netilmicin sulfate inj according to claim 1, it is characterized in that: at air purity is under hundred grades of conditions, will prepare in right amount with water for injection to be cooled to below 30 ℃; Logical nitrogen deoxygenation adds antioxidant, the chelating agent of recipe quantity and makes dissolving fully in the water for injection, and the netilmicin sulfate of recipe quantity is added in the above-mentioned solution; Stirring makes dissolving fully; With the needle-use activated carbon absorption of 0.05～0.2% (g/ml) concentration, take off charcoal with the filter just of 1 μ m filter, 1 cover, regulate pH between 5.3～5.7 with liquor sodii citratis; Stir; Be settled to full dose with water for injection, with 0.22/0.22 μ m polypropylene foldable filter element filter 1 cover and the 2 cover fine straining degerming of 0.22/0.22 μ m microporous membrane of polyethersulfone candle filter, embedding under hundred grades of conditions (overall process inflated with nitrogen); Auxiliary sterilization below 100 ℃, lamp inspection, packing promptly get.
3. the method for preparing of netilmicin sulfate inj according to claim 1 and 2, it is characterized in that: the antioxidant of use comprises sodium sulfite, sodium pyrosulfite, preferred sodium sulfite; The chelating agent that uses comprises calcium disodium edetate, disodium edetate, preferred calcium disodium edetate; The pH value regulator that uses is liquor sodii citratis, preferred 10% liquor sodii citratis.
4. the method for preparing of netilmicin sulfate inj according to claim 1 and 2 is characterized in that: from being formulated into filling and sealing is that the exposed operation of medicinal liquid adopts sterile production technology.
5. the method for preparing of netilmicin sulfate inj according to claim 1 and 2 is characterized in that: preparation is cooled to below 30 ℃ with water for injection and towards the nitrogen deoxygenation.
6. the method for preparing of netilmicin sulfate inj according to claim 1 and 2 is characterized in that: production process adopts ultrafiltration to combine with aseptic filtration.
7. the method for preparing of netilmicin sulfate inj according to claim 1 and 2 is characterized in that: production process employing " aseptic+auxiliary sterilization " method for preparing, wherein auxiliary sterilization below 100 ℃, preferred 100 ℃, 30 minutes sterilising conditions.
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| CN2010105209373A CN102451154A (en) | 2010-10-14 | 2010-10-14 | Netilmicin sulfate injection and preparation method thereof |
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| CN2010105209373A CN102451154A (en) | 2010-10-14 | 2010-10-14 | Netilmicin sulfate injection and preparation method thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104606132A (en) * | 2015-01-30 | 2015-05-13 | 上海华源安徽锦辉制药有限公司 | Method for dissolving ambroxol hydrochloride raw materials |
| CN105147599A (en) * | 2015-09-21 | 2015-12-16 | 成都天台山制药有限公司 | Netilmicin sulfate injection and preparing method |
| CN105213301A (en) * | 2015-09-21 | 2016-01-06 | 成都天台山制药有限公司 | Netilmicin sulfate inj and quality control method thereof |
| CN111686072A (en) * | 2020-06-28 | 2020-09-22 | 江苏吴中医药集团有限公司 | Linezolid injection and preparation method thereof |
| CN113171348A (en) * | 2021-04-28 | 2021-07-27 | 海南通用康力制药有限公司 | Preparation method of netilmicin sulfate sterile powder injection for injection |
| CN114177140A (en) * | 2021-12-10 | 2022-03-15 | 卓和药业集团股份有限公司 | Netilmicin sulfate aerosol |
| WO2022166933A1 (en) * | 2021-02-05 | 2022-08-11 | 上海科技大学 | Anti-coronavirus application of compound |
| CN115671044A (en) * | 2022-11-29 | 2023-02-03 | 江苏四环生物制药有限公司 | Netilmicin sulfate injection and preparation method thereof |
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| CN101461783A (en) * | 2008-12-16 | 2009-06-24 | 海南美大制药有限公司 | Netilmicin sulphate nano micelle preparation for intravenous injection and preparation method thereof |
| WO2009108406A2 (en) * | 2008-01-10 | 2009-09-03 | Trustees Of Boston University | Engineered bacteriophages as adjuvants for antimicrobial agents and compositions and methods of use thereof |
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104606132A (en) * | 2015-01-30 | 2015-05-13 | 上海华源安徽锦辉制药有限公司 | Method for dissolving ambroxol hydrochloride raw materials |
| CN104606132B (en) * | 2015-01-30 | 2017-09-22 | 上海华源安徽锦辉制药有限公司 | A kind of dissolving method of ambroxol hydrochloride raw material |
| CN105147599A (en) * | 2015-09-21 | 2015-12-16 | 成都天台山制药有限公司 | Netilmicin sulfate injection and preparing method |
| CN105213301A (en) * | 2015-09-21 | 2016-01-06 | 成都天台山制药有限公司 | Netilmicin sulfate inj and quality control method thereof |
| CN105213301B (en) * | 2015-09-21 | 2018-07-27 | 成都天台山制药有限公司 | Netilmicin sulfate injection and its quality control method |
| CN105147599B (en) * | 2015-09-21 | 2018-07-27 | 成都天台山制药有限公司 | Netilmicin sulfate injection and preparation method |
| CN111686072A (en) * | 2020-06-28 | 2020-09-22 | 江苏吴中医药集团有限公司 | Linezolid injection and preparation method thereof |
| WO2022166933A1 (en) * | 2021-02-05 | 2022-08-11 | 上海科技大学 | Anti-coronavirus application of compound |
| CN113171348A (en) * | 2021-04-28 | 2021-07-27 | 海南通用康力制药有限公司 | Preparation method of netilmicin sulfate sterile powder injection for injection |
| CN114177140A (en) * | 2021-12-10 | 2022-03-15 | 卓和药业集团股份有限公司 | Netilmicin sulfate aerosol |
| CN115671044A (en) * | 2022-11-29 | 2023-02-03 | 江苏四环生物制药有限公司 | Netilmicin sulfate injection and preparation method thereof |
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Application publication date: 20120516 |