CN1830440A - Metronidazule injection and its preparation method and use - Google Patents
Metronidazule injection and its preparation method and use Download PDFInfo
- Publication number
- CN1830440A CN1830440A CN 200510051481 CN200510051481A CN1830440A CN 1830440 A CN1830440 A CN 1830440A CN 200510051481 CN200510051481 CN 200510051481 CN 200510051481 A CN200510051481 A CN 200510051481A CN 1830440 A CN1830440 A CN 1830440A
- Authority
- CN
- China
- Prior art keywords
- metronidazole
- injection
- gets
- fully
- water
- 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
A liquid injection of metronidazole for treating anaerobe infection is prepared from metronidazole, sodium chloride, prepanediol, and the water for injection through dissolving the metronidazole in propanediol and conventional steps.
Description
Technical field
The present invention relates to a kind of metronidazole injection and its production and use, belong to chemical field of medicaments.
Background technology
The metronidazole injection Main Ingredients and Appearance is a metronidazole, and chemical name 2-methyl-5-nitro imidazoles-1-ethanol is white or yellowish crystallization or crystalline powder, have little smelly, bitter in the mouth and slightly salty.Molten in the ethanol part omitted, slightly soluble in water or chloroform, soluble,very slightly in ether, fusing point are 159～163 ℃.
Metronidazole has the strong antibiotic effect to most of anaerobe, but aerobe and facultative anaerobe there is not effect, antimicrobial spectrum comprises bacteroides fragilis and other Bacteroides, fusiform bacilarmature, aerogenesis clostridium, Eubacterium, Wei Rong coccus, dyspepsiacoccus and peptostreptococcus etc., and actinomyces, Lactobacillus, propionibacterium are to this product drug resistance.The a little higher than Mlc of its bacteriocidal concentration.
This product still can suppress the ameba redox reaction, and the protozoon nitrogen chain is ruptured.In vitro tests proves, when drug level was 1～2mg/L, amoeba histolytica form can take place in 6～20 hours changes, and all is killed in 24 hours, when concentration is 0.2mg/L, can kill amoeba histolytica in 72 hours.This product has the powerful effect of killing infusorian, and its mechanism is not bright.Show by acute toxicity testing and sub-acute toxicity test: metronidazole does not all have influence to hemopoietic system, liver, renal function and blood fat.
At present, be that main active is applied to clinical having with the metronidazole: Metronidazole Tablet, metronidazole effervescent tablet, metronidazole suppository, metronidazole capsule, metronidazole glucose infusion solutions, metronidazole injection etc.
Metronidazole injection is mainly used in the treatment of anaerobic infection.Intravenous drip (1) adult usual amounts: maintenance dose is by body weight 7.5mg/kg by body weight 15mg/kg (the 70kg adult is 1g) first for anaerobic infection, intravenously administrable, and intravenous drip in per 6～8 hours once.(2) children's's usual amounts: the injected dose of anaerobic infection is with the adult.
The metronidazole that contains 5mg so far in the metronidazole injection with small volume among every ml, because dissolubility slightly soluble in water of metronidazole, can not make the big preparation of concentration, clinical use is extremely inconvenient, 10 of once minimum uses, can only rely on the transfusion high capacity to satisfy injected dose, infusion preparation itself is inconvenient to transport, injection with small volume of the present invention can be produced the preparation of big concentration, concentration is up to the metronidazole that contains 25mg among every ml, and once using only needs 2 positive usual amounts that can satisfy human body.
Summary of the invention
The object of the present invention is to provide a kind of metronidazole injection, during clinical use, 2 positive usual amounts that can satisfy human body only once.
A further object of the present invention is to provide a kind of preparation method of metronidazole injection.
Another object of the present invention is to provide of the application of a kind of metronidazole injection at disease medicaments such as preparation treatment anaerobic infections.
A kind of metronidazole injection of the present invention comprises metronidazole, sodium chloride, propylene glycol, water for injection, it is characterized in that, in order effectively to dissolve metronidazole, uses the propylene glycol of 1～50 times of amount, and sodium chloride is 0.4～0.9%.
For guaranteeing the quality of the pharmaceutical preparations, the employed filter membrane of technical process of the present invention is organic filter membrane.
The preparation method of a kind of metronidazole injection of the present invention, comprise the steps: earlier with the propylene glycol dissolving of metronidazole with 1～50 times of amount, other gets 1～100 times water for injection dissolving sodium chloride, and two kinds of medicinal liquids are mixed, and regulates pH value, sterilizes and make metronidazole injection.
The preparation method of metronidazole injection of the present invention specifically comprises the steps:
Earlier metronidazole is dissolved in the propylene glycol of 1～50 times of amount, gets medicinal liquid A; Other gets the water for injection of 1～100 times of amount, and adding sodium chloride fully stirs and makes dissolving fully, gets medical liquid B; With medicinal liquid A and the abundant mix homogeneously of medical liquid B, add 0.01%～0.5% active carbon, heated and boiled 15～30 minutes, decarbonization filtering, last adjust pH is 4.5～7.0, fill behind end-filtration, sterilization, lamp inspection, packing form injection.
The pH of metronidazole injection of the present invention is 4.5～7.0, is preferably pH5.8～6.2, and the pH value regulator can be selected this area regulator commonly used for use, such as 10% sodium hydroxide or 10% hydrochloric acid solution.
Sterilizing installation and technology that described sterilization can adopt those skilled in the art to use always.For example, use water-bath sterilization or steam sterilization, sterilized 30-45 minute down at 100-110 ℃.
Preferably, the preparation method of metronidazole injection of the present invention comprises the steps:
Earlier metronidazole is dissolved in the propylene glycol of 20～30 times of amounts, gets medicinal liquid A; Other gets the water for injection of 10～30 times of amounts, and adding sodium chloride fully stirs and makes dissolving fully, gets medical liquid B; With medicinal liquid A and the abundant mix homogeneously of medical liquid B, add 0.01%～0.5% active carbon, heated and boiled 15～30 minutes, decarbonization filtering, last adjust pH is 5.8～6.2, fill behind end-filtration, sterilization, lamp inspection, packing form injection.
The metronidazole injection that adopts preparation method of the present invention and get, character is colourless or almost colourless clear liquid, specification can be 10ml: 50mg, 20ml: 100mg, 20ml: 500mg, 100ml: 500mg, 250ml: 500mg, and most preferred specification is 20ml: 500mg.
Be mainly used in the treatment of anaerobic infection during metronidazole injection clinical practice of the present invention.Intravenous drip (1) adult usual amounts: maintenance dose is by body weight 7.5mg/kg by body weight 15mg/kg (the 70kg adult is 1g) first for anaerobic infection, intravenously administrable, and intravenous drip in per 6～8 hours once.(2) children's's usual amounts: the injected dose of anaerobic infection is with the adult.But injection long term administration of the present invention.
Metronidazole has the strong antibiotic effect to most of anaerobe, but aerobe and facultative anaerobe there is not effect, antimicrobial spectrum comprises bacteroides fragilis and other Bacteroides, fusiform bacilarmature, aerogenesis clostridium, Eubacterium, Wei Rong coccus, dyspepsiacoccus and peptostreptococcus etc., and actinomyces, Lactobacillus, propionibacterium are to this product drug resistance.The a little higher than Mlc of its bacteriocidal concentration.
This product still can suppress the ameba redox reaction, and the protozoon nitrogen chain is ruptured.In vitro tests proves, when drug level was 1～2mg/L, amoeba histolytica form can take place in 6～20 hours changes, and all is killed in 24 hours, when concentration is 0.2mg/L, can kill amoeba histolytica in 72 hours.This product has the powerful effect of killing infusorian, and its mechanism is not bright.
The specific embodiment
Following embodiment further describes the present invention, but described embodiment only is used to illustrate the present invention rather than restriction the present invention.
Embodiment 1
Earlier metronidazole is dissolved in the propylene glycol of 10 times of amounts, gets medicinal liquid A; Other gets the water for injection of 10 times of amounts, add 0.4% sodium chloride and fully stir and make fully dissolving, medical liquid B; With medicinal liquid A and the abundant mix homogeneously of medical liquid B, add 0.02% active carbon, heated and boiled 15 minutes, decarbonization filtering, standardize solution, last adjust pH is 4.8, fill behind end-filtration, sterilization, lamp inspection, packing form injection.
Embodiment 2
Earlier metronidazole is dissolved in the propylene glycol of 20 times of amounts, gets medicinal liquid A; Other gets the water for injection of 20 times of amounts, add 0.8% sodium chloride and fully stir and make fully dissolving, medical liquid B; With medicinal liquid A and the abundant mix homogeneously of medical liquid B, add 0.03% active carbon, heated and boiled 20 minutes, decarbonization filtering, standardize solution, last adjust pH is 5.2, fill behind end-filtration, sterilization, lamp inspection, packing form injection.
Embodiment 3
Earlier metronidazole is dissolved in the propylene glycol of 30 times of amounts, gets medicinal liquid A; Other gets the water for injection of 30 times of amounts, add 0.9% sodium chloride and fully stir and make fully dissolving, medical liquid B; With medicinal liquid A and the abundant mix homogeneously of medical liquid B, add 0.06% active carbon, heated and boiled 20 minutes, decarbonization filtering, standardize solution, last adjust pH is 6.5, fill behind end-filtration, sterilization, lamp inspection, packing form injection.
Embodiment 4
Earlier metronidazole is dissolved in the propylene glycol of 50 times of amounts, gets medicinal liquid A; Other gets the water for injection of 80 times of amounts, add 0.7% sodium chloride and fully stir and make fully dissolving, medical liquid B; With medicinal liquid A and the abundant mix homogeneously of medical liquid B, add 0.3% active carbon, heated and boiled 20 minutes, decarbonization filtering, standardize solution, last adjust pH is 6.8, fill behind end-filtration, sterilization, lamp inspection, packing form injection.
Embodiment 5
Earlier metronidazole is dissolved in the propylene glycol of 50 times of amounts, gets medicinal liquid A; Other gets the water for injection of 40 times of amounts, add 0.85% sodium chloride and fully stir and make fully dissolving, medical liquid B; With medicinal liquid A and the abundant mix homogeneously of medical liquid B, add 0.5% active carbon, heated and boiled 20 minutes, decarbonization filtering, standardize solution, last adjust pH is 6.0, fill behind end-filtration, sterilization, lamp inspection, packing form injection.
Experimental example 1
This experimental example is most preferably specification 20ml of injection of the present invention: the detection of relevant every gainer under 500mg outward appearance, pH value, the injection item.
Character: medicine composition injection of the present invention is colourless or almost colourless clear liquid.
PH value: measure according to two appendix VI of Chinese Pharmacopoeia version in 2000 H, medicine composition injection pH value of the present invention is 4.5-7.0, meets quality standard.
Bacterial endotoxin: get this product, contain the endotoxin amount among inspection (two appendix XI of Chinese Pharmacopoeia version in 2000 E mensuration) every 1ml should be less than 0.35EU in accordance with the law, and this product is up to specification.
Aseptic: get this product, check (two appendix XI of Chinese Pharmacopoeia version in 2000 H mensuration) in accordance with the law, this product is up to specification.
Clarity: get this product, check that according to " clarity test detailed rules and regulations and criterion " this product is up to specification.
Experimental example 2
This experimental example is most preferably specification 20ml of injection of the present invention: the qualitative determination of composition among the 500mg.
(1) get this product an amount of (being equivalent to metronidazole 10mg approximately),, according to the test of the discriminating (1) under the metronidazole item, show identical reaction.
(2) get this product an amount of (being equivalent to metronidazole 0.1g approximately), put evaporate to dryness in the water-bath, residue shows identical result according to the test of the discriminating (2) under the metronidazole item.
(3) get solution under the assay item, (two appendix IV of Chinese Pharmacopoeia version in 2000 A measures, and at the wavelength place of 277nm absorption maximum is arranged, and at the wavelength place of 241nm minimal absorption is arranged according to spectrophotography.
(4) this product shows sodium salt and muriatic identification.
Injection of the present invention is all up to specification with the inspection of beginning a project.
Experimental example 3
This experimental example is for being most preferably specification 20ml of injection of the present invention: muriatic mensuration among the 500mg.
Precision is measured this product an amount of (being equivalent to metronidazole 50mg approximately) and is added water to 50ml, add 5～8 of 2% dextrin solution 5ml, calcium carbonate 0.1g and fluorescein indicator solutions, after shaking up,, become blush by yellow green to turbid solution with silver nitrate titration liquid (0.1mol/L) titration.Consume silver nitrate titration liquid (0.1mol/L) and should be 13.2～14.6ml or 35.1～38.8ml (specification of 250ml: 500mg) or 2.1～5.4ml (specification of 20ml: 500mg).
Injection of the present invention is through three batches mensuration, and chloride is checked up to specification.
Experimental example 4
This experimental example is the most preferably quantitative assay of specification 20ml: 500mg of injection of the present invention.
It is an amount of that precision is measured this product, adds hydrochloric acid solution (9 → 1000) and quantitatively be diluted to the solution that contains metronidazole 12.5 μ g among every 1ml approximately, according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), measures trap at the wavelength place of 277nm, presses C
6H
9N
3O
3Absorptance (E
1% 1cm) be 377 calculating, promptly.
Injection of the present invention is through three batches assay, result's following (seeing Table 1):
Table 1: metronidazole assay result
| Lot number (20ml: 500mg) | Account for labelled amount % |
| 20040601 | 99.6 |
| 20040602 | 102.8 |
| 20040603 | 100.3 |
Comparative example 1
The metronidazole injection clarity that the explanation of this comparative example is produced with process using propylene glycol processing of the present invention is better than producing with conventional compound method.
Table 2: the comparison of technology of the present invention and common process clarity
| One technology of the present invention | Two common process | |
| Method for making | Earlier metronidazole is dissolved in the propylene glycol of 30 times of amounts, gets medicinal liquid A; Other gets the water for injection of 30 times of amounts, add 0.85% sodium chloride and fully stir and make fully dissolving, medical liquid B; With medicinal liquid A and the abundant mix homogeneously of medical liquid B, the active carbon of adding 0.2%, heated and boiled 20 minutes, decarbonization filtering, standardize solution, last adjust pH is 6.0, fill behind end-filtration, sterilization, lamp inspection, packing forms injection. | A) get the fresh water for injection of amount of preparation 40%, add the sodium chloride in the prescription, fully stir and make dissolving fully, add the metronidazole in the prescription, fully stir and make dissolving fully, add 0.2% active carbon, decarbonization filtering, standardize solution, regulate pH6.0, intermediate products after the assay was approved, with medicinal liquid through the end-filtration fill, sterilization, lamp inspection, pack the metronidazole injection finished product. |
| Clarity (is closed | Get 200 of this product, by " clarity test is thin | Get 200 of this product, by " clarity test |
| The lattice rate is greater than 95%) | Then and criterion " check: 20040601 batches: qualification rate 99.6%.20040602 batches: qualification rate 99.5%.20040603 batches: qualification rate 99.5%.The chips of glass factor of breaking and producing because of ampoule when getting rid of fill, after this PROCESS FOR TREATMENT, the clarity qualification rate reaches 100% substantially. | Detailed rules and regulations and criterion " check: 220040601 batches: qualification rate 79.8%.20040602 batches: qualification rate 79.5%.20040603 batches: qualification rate 80.5%.The chips of glass factor of breaking and producing because of ampoule when getting rid of fill, after this PROCESS FOR TREATMENT, the clarity qualification rate is between 85～87%. |
Comparative example 2
This comparative example explanation has identical curative effect when using metronidazole injection clinical practice with common process production clinically with metronidazole injection of the present invention, does not have other untoward reaction.
Table 3: the comparison of technology of the present invention and common process clinical efficacy
| Metronidazole injection of the present invention | The metronidazole injection of common process | |
| Usage and dosage | (1) adult's usual amounts: anaerobic infection, maintenance dose is by body weight 7.5mg/kg by body weight 15mg/kg (the 70kg adult is 1g) first for intravenously administrable, and intravenous drip in per 6～8 hours once.(2) children's's usual amounts: the injected dose of anaerobic infection is with the adult. | (1) adult's usual amounts: anaerobic infection, maintenance dose is by body weight 7.5mg/kg by body weight 15mg/kg (the 70kg adult is 1g) first for intravenously administrable, and intravenous drip in per 6～8 hours once.(2) children's's usual amounts: the injected dose of anaerobic infection is with the adult. |
| Clinical use | Treat 53 routine vaginitis patients | Treat 40 vaginitis patients |
| Other untoward reaction are observed | Do not have. | Do not have. |
| Zest is observed | No pain phenomenon. | No pain phenomenon. |
Claims (5)
1. a metronidazole injection comprises metronidazole, sodium chloride, propylene glycol, water for injection, it is characterized in that, for guaranteeing that metronidazole can fully be dissolved in the water for injection, needs with the propylene glycol of 1～50 times of amount metronidazole fully to be dissolved.
2. a kind of metronidazole injection according to claim 1 is characterized in that described sodium chloride content is preferably 0.4～0.9%.
3. according to any one metronidazole injection in claim 1 or 2, it is characterized in that described filter membrane all adopts organic filter membrane to filter.
4. the preparation method of metronidazole injection according to claim 1 is characterized in that, comprises the steps: earlier metronidazole to be dissolved in the propylene glycol of 1～50 times of amount, gets medicinal liquid A; Other gets the water for injection of 1～100 times of amount, and adding sodium chloride fully stirs and makes dissolving fully, gets medical liquid B; With medicinal liquid A and the abundant mix homogeneously of medical liquid B, add 0.01%～0.5% active carbon, heated and boiled 15～30 minutes, decarbonization filtering, last adjust pH is 4.5～7.0, fill behind end-filtration, sterilization, lamp inspection, packing form injection.
5. metronidazole injection according to claim 1 is used for the treatment of anaerobic infection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510051481 CN1830440A (en) | 2005-03-08 | 2005-03-08 | Metronidazule injection and its preparation method and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510051481 CN1830440A (en) | 2005-03-08 | 2005-03-08 | Metronidazule injection and its preparation method and use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1830440A true CN1830440A (en) | 2006-09-13 |
Family
ID=36993042
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510051481 Pending CN1830440A (en) | 2005-03-08 | 2005-03-08 | Metronidazule injection and its preparation method and use |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1830440A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102274167A (en) * | 2011-07-20 | 2011-12-14 | 蚌埠丰原涂山制药有限公司 | Method for preparing metronidazole injection |
| CN102552127A (en) * | 2012-01-31 | 2012-07-11 | 石家庄开发区博欣医药科技开发有限公司 | Ornidazole injection |
| CN106619501A (en) * | 2017-01-02 | 2017-05-10 | 江苏恒丰强生物技术有限公司 | Metronidazole glucose injection and preparation method thereof |
| CN108096198A (en) * | 2017-12-26 | 2018-06-01 | 金华智济药物科技合伙企业（有限合伙） | Novel antibacterial pharmaceutical composition when prevention and treatment aerobic bacteria and anaerobic bacteria mixed infection and preparation method thereof |
| CN111012738A (en) * | 2019-11-26 | 2020-04-17 | 江苏恒丰强生物技术有限公司 | Metronidazole injection and preparation method thereof |
| WO2020259464A1 (en) * | 2019-06-28 | 2020-12-30 | 石家庄四药有限公司 | Metronidazole and sodium chloride injection and preparation method therefor |
-
2005
- 2005-03-08 CN CN 200510051481 patent/CN1830440A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102274167A (en) * | 2011-07-20 | 2011-12-14 | 蚌埠丰原涂山制药有限公司 | Method for preparing metronidazole injection |
| CN102274167B (en) * | 2011-07-20 | 2013-01-09 | 安徽丰原淮海制药有限公司 | Method for preparing metronidazole injection |
| CN102552127A (en) * | 2012-01-31 | 2012-07-11 | 石家庄开发区博欣医药科技开发有限公司 | Ornidazole injection |
| CN106619501A (en) * | 2017-01-02 | 2017-05-10 | 江苏恒丰强生物技术有限公司 | Metronidazole glucose injection and preparation method thereof |
| CN108096198A (en) * | 2017-12-26 | 2018-06-01 | 金华智济药物科技合伙企业（有限合伙） | Novel antibacterial pharmaceutical composition when prevention and treatment aerobic bacteria and anaerobic bacteria mixed infection and preparation method thereof |
| WO2020259464A1 (en) * | 2019-06-28 | 2020-12-30 | 石家庄四药有限公司 | Metronidazole and sodium chloride injection and preparation method therefor |
| CN111012738A (en) * | 2019-11-26 | 2020-04-17 | 江苏恒丰强生物技术有限公司 | Metronidazole injection and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1138541C (en) | Pharmaceutically stable oxaliplatinum prepn. | |
| CN1314396C (en) | Application of levoornidazole in preparation of anti anaerobic bacteria infection medicine | |
| CN1830440A (en) | Metronidazule injection and its preparation method and use | |
| CN1686116A (en) | Levo ornidazole vein administration agent and its preparation method | |
| CN101919811A (en) | Levetiracetam injection and preparation method thereof | |
| CN102772360A (en) | Doxycycline hydrochloride injection for animals and preparation method for doxycycline hydrochloride injection | |
| CN1823768A (en) | Cimetidine freeze dried composition | |
| CN1813739A (en) | Nalmefene hydro chloride lyophilized powder formulation for injection | |
| CN117379378A (en) | Compound amoxicillin soluble powder for livestock and preparation process thereof | |
| CN1429558A (en) | Mannosan peptide injection and its preparation and use method | |
| CN109481459B (en) | Compound electrolyte glucose injection and preparation method thereof | |
| CN1830428A (en) | Sodium ferulate injection and its preparation method | |
| CN105769756B (en) | A kind of fumaric acid Sitafloxacin hydrate injection and preparation method thereof | |
| CN1739530A (en) | Aspirin-Al-lysine for injection | |
| CN101336903B (en) | Preparation method of (s)-ornidazole disodium phosphate intravenous preparation for injection | |
| CN1830426A (en) | New houttuynine sodium bisulfite injection and its preparation method and use | |
| CN1186094C (en) | Piracetam medicine composition with function of promoting thinking and memory and its prepn | |
| CN107875154B (en) | Composition containing piperacillin, pharmaceutical preparation and application thereof | |
| CN1830434A (en) | Preparation method of troxerutin injection | |
| US11534438B2 (en) | Composition containing piperacillin, pharmaceutical formulation thereof and use thereof | |
| CN1231223C (en) | Breviscapine infusion preparation and its preparing method | |
| CN1706391A (en) | Terramycin suspension emulsion | |
| CN1555788A (en) | Thio pronine transfursion liquid and its preparation method | |
| CN1254244C (en) | Balofoxacin liquid preparation preparing method and its use | |
| CN104983678A (en) | Ornidazole infusion preparation and preparation technology 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 | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Xu Wenjie Document name: Notification of the application for patent for invention to go through the substantive examination procedure |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |