CN113181113A - Preparation method of metronidazole sodium chloride injection - Google Patents
Preparation method of metronidazole sodium chloride injection Download PDFInfo
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- CN113181113A CN113181113A CN202110465351.XA CN202110465351A CN113181113A CN 113181113 A CN113181113 A CN 113181113A CN 202110465351 A CN202110465351 A CN 202110465351A CN 113181113 A CN113181113 A CN 113181113A
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- metronidazole
- sodium chloride
- injection
- preparation
- prescription
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
Abstract
The invention relates to the technical field of metronidazole medicaments, in particular to a preparation method of a metronidazole sodium chloride injection, which comprises the following steps of (1) sequentially adding injection water, citric acid, anhydrous disodium hydrogen phosphate, metronidazole and sodium chloride into a diluting preparation tank for diluting preparation, stirring for dissolving, and supplementing the injection water to the full amount of a prescription, wherein the metronidazole is pureness; (2) stirring uniformly, sampling and detecting; (3) filtration, embedment, sterilization, packing, whole preparation process adopts the one-step preparation of rare prescription, shortens the production time greatly, reduces the risk of microbial contamination, avoids thick prescription in-process cardinal remedy metronidazole to be filtered, and citric acid, anhydrous disodium hydrogen phosphate can adjust the pH value in the prescription, need not to add the PH regulator specially, satisfy the quality requirement, have reduced the risk of adjusting the PH in-process and have introduced impurity, can avoid the PH regulator to add the inhomogeneous condition of back stirring to appear simultaneously.
Description
Technical Field
The invention relates to the technical field of metronidazole medicines, and in particular relates to a preparation method of a metronidazole sodium chloride injection.
Background
The metronidazole raw material medicine is a nitroimidazole type antibiotic raw material medicine, and can effectively treat serious infection caused by sensitive anaerobic bacteria, mixed infection of aerobic bacteria and anaerobic bacteria and bacteroides fragilis infection with drug resistance of clindamycin, chloramphenicol and penicillin after being prepared into an injection.
Most preparation methods of metronidazole sodium chloride injection at present are carried out for adopting thick two-step mode of joining in marriage after filtration to rare joining in marriage, need use two preparation jars at this in-process, thick jar and rare joining in marriage jar promptly, this kind of method exists and prepares time for a long time, the problem that the microorganism pollution risk is high, and because the solubility of metronidazole bulk drug in aqueous is general, can have undissolved metronidazole, adopt thick filtration after joining in marriage to change rare joining in marriage the mode, can filter undissolved metronidazole and lead to its content to reduce, and can not reach the quality standard.
Disclosure of Invention
The invention aims to provide a preparation method of metronidazole sodium chloride injection, which solves the technical problems that the preparation process of the existing metronidazole sodium chloride injection is time-consuming, increases microbial pollution and can not reach the quality standard.
The invention is realized by the following technical scheme: the method comprises the following steps:
(1) sequentially adding water for injection, citric acid, anhydrous disodium hydrogen phosphate, metronidazole and sodium chloride into a diluting preparation tank for diluting preparation, stirring for dissolving, and adding water for injection to the full amount of the prescription, wherein the metronidazole is pure;
(2) stirring uniformly, sampling and detecting;
(3) filtering, bottling, sterilizing, and packaging.
Preferably, the method comprises the following steps:
(1) adding 70-80% of injection water in the total volume of the prescription into a preparation tank, sequentially adding citric acid, anhydrous disodium hydrogen phosphate, metronidazole and sodium chloride in the prescription, stirring to dissolve, and supplementing the injection water to the total volume of the prescription, wherein the metronidazole is purer;
(2) stirring uniformly, sampling and detecting;
(3) filtering, bottling, sterilizing, and packaging.
Preferably, the preparation tank is a letdown tank.
Preferably, the weight ratio of the citric acid to the anhydrous disodium hydrogen phosphate to the metronidazole to the sodium chloride is 0.024-0.026:0.045-0.050:0.5: 0.8.
Preferably, the weight ratio of the citric acid to the anhydrous disodium hydrogen phosphate to the metronidazole to the sodium chloride is 0.024:0.045:0.5: 0.8.
Preferably, the weight ratio of the citric acid to the anhydrous disodium hydrogen phosphate to the metronidazole to the sodium chloride is 0.026:0.050:0.5: 0.8.
Preferably, the sterilization conditions in step (3) are sterilization at a temperature of 121 ℃ for 12 min.
Preferably, the pH value of the injection solution after the uniform stirring in the step (2) is 4.5-7.0.
Compared with the prior art, the invention has the following advantages and beneficial effects:
(1) the whole preparation process adopts a one-step preparation method of dilute preparation, so that the production time is greatly shortened, the risk of microbial contamination is reduced, the risk of filtering metronidazole serving as a main drug in the concentrated preparation process is avoided, the pH value can be adjusted by citric acid and anhydrous disodium hydrogen phosphate in the formula, a pH regulator is not required to be specially added for pH adjustment, the quality requirement is met, the risk of introducing impurities in the pH adjustment process is reduced, and the condition of uneven stirring after the pH regulator is added can be avoided.
(2) The temperature is not required to be controlled in the preparation process, the metronidazole and other auxiliary materials can be well dissolved by utilizing the temperature of the injection water, and the risk that impurities such as nitrite and the like are increased due to heating and boiling for ensuring the complete dissolution of the main materials in the existing concentration preparation process is avoided.
(3) The preparation process does not use activated carbon, so that the condition that the main content is reduced due to the adsorption of the activated carbon on the main components of the liquid medicine is avoided under the condition of ensuring the sterility, and meanwhile, the treatment cost of the activated carbon after use is reduced.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following examples, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not used as limitations of the present invention.
Example 1: a preparation method of metronidazole sodium chloride injection comprises the following steps:
(1) adding injection water accounting for 70-80% of the total volume of the prescription into a diluting preparation tank, sequentially adding citric acid, anhydrous disodium hydrogen phosphate, metronidazole and sodium chloride according to the prescription, stirring and dissolving, and supplementing the injection water to the total volume of the prescription, wherein metronidazole is pure;
(2) stirring uniformly, sampling and detecting the pH value, the character, the content of metronidazole, sodium chloride and the like;
(3) filtering the liquid medicine after the liquid medicine is qualified, filling and sealing, sterilizing at the temperature of 121 ℃ for 12min, and packaging.
Wherein the weight ratio of the citric acid to the anhydrous disodium hydrogen phosphate to the metronidazole to the sodium chloride is 0.024-0.026:0.045-0.050:0.5:0.8, and can be 0.024:0.045:0.5:0.8 or 0.026:0.050:0.5:0.8, the volume of the water for the first injection can account for 70%, 80% or 75% of the total volume of the prescription, and the PH value of the injection is 4.5-7.0 after the water for the first injection is added to the full prescription and is uniformly stirred.
Example 2: a preparation method of metronidazole sodium chloride injection comprises the following steps:
(1) adding 0.7L of water for injection into a diluting preparation tank, sequentially adding 0.24g of citric acid, 0.45g of anhydrous disodium hydrogen phosphate, 5g of metronidazole and 8g of sodium chloride, stirring until the citric acid, the anhydrous disodium hydrogen phosphate, the metronidazole and the sodium chloride are completely dissolved, adding 1L of water for injection, continuously stirring uniformly, sampling to determine the pH value, the character, the content of the metronidazole and the sodium chloride of the liquid medicine, and simultaneously inspecting related impurities of the metronidazole;
(2) filtering the prepared liquid medicine, filling, sterilizing at 121 ℃ for 12 minutes, and packaging.
The following table one shows the detection results of the liquid medicine in example 2, and the properties of the liquid medicine, PH, metronidazole content, nitrite content and impurity content all meet the quality standards.
Watch 1
Example 3: a preparation method of metronidazole sodium chloride injection comprises the following steps:
(1) adding 0.7L of water for injection into a diluting preparation tank, sequentially adding 0.26g of citric acid, 0.5g of anhydrous disodium hydrogen phosphate, 5g of metronidazole and 8g of sodium chloride, stirring until the citric acid, the anhydrous disodium hydrogen phosphate, the metronidazole and the sodium chloride are completely dissolved, adding 1L of water for injection, continuously stirring uniformly, sampling to determine the pH value, the character, the content of the metronidazole and the sodium chloride of the liquid medicine, and simultaneously inspecting related impurities of the metronidazole;
(2) filtering the liquid medicine after the liquid medicine is qualified, filling and sealing the liquid medicine, sterilizing the liquid medicine for 12 minutes at 121 ℃, and packaging the liquid medicine.
The second table below shows the test results of the liquid medicine in example 3, and the properties, PH, metronidazole content, nitrite content and impurity content of the liquid medicine all meet the quality standards.
Watch two
Example 4: a preparation method of metronidazole sodium chloride injection comprises the following steps:
(1) adding 3.5L of water for injection into a diluting preparation tank, sequentially adding 1.25g of citric acid, 2.38g of anhydrous disodium hydrogen phosphate, 25g of metronidazole and 40g of sodium chloride, stirring until the citric acid, the anhydrous disodium hydrogen phosphate, the metronidazole and the sodium chloride are completely dissolved, adding injection water to 5L, continuously stirring uniformly, taking a sample to determine the pH value, the character, the content of the metronidazole and the sodium chloride of the liquid medicine, and simultaneously inspecting related impurities of the metronidazole;
(2) filtering the prepared liquid medicine, filling, sterilizing at 121 ℃ for 12 minutes, and packaging.
The third table below shows the test results of the liquid medicine in example 4, and the properties of the liquid medicine, PH, metronidazole content, sodium chloride content, osmotic pressure, bacterial endotoxin content and impurity content all meet the quality standards.
Watch III
Example 5: a preparation method of metronidazole sodium chloride injection comprises the following steps:
(1) adding 4300L of water for injection into a diluting preparation tank, sequentially adding 1.5kg of citric acid, 2, 8kg of anhydrous disodium hydrogen phosphate, 30kg of metronidazole and 48kg of sodium chloride, stirring until the citric acid, the anhydrous disodium hydrogen phosphate, the metronidazole and the sodium chloride are completely dissolved, adding injection water to 5900L, continuously stirring uniformly, sampling to determine the pH value, the character, the content of the metronidazole and the sodium chloride of the liquid medicine, and simultaneously inspecting related impurities of the metronidazole;
(2) filtering the prepared liquid medicine, filling, sterilizing at 121 ℃ for 12 minutes, and packaging.
The following table four shows the detection results of the liquid medicine in example 5, and the properties of the liquid medicine, PH, metronidazole content, sodium chloride content, osmotic pressure, bacterial endotoxin content and impurity content all meet the quality standards.
Watch four
The above-mentioned embodiments, objects, technical solutions and advantages of the present invention are further described in detail, it should be understood that the above-mentioned embodiments are only exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (7)
1. A preparation method of metronidazole sodium chloride injection is characterized by comprising the following steps:
(1) sequentially adding water for injection, citric acid, anhydrous disodium hydrogen phosphate, metronidazole and sodium chloride into a diluting preparation tank for diluting preparation, stirring for dissolving, and adding water for injection to the full amount of the prescription, wherein the metronidazole is pure;
(2) stirring uniformly, sampling and detecting;
(3) filtering, bottling, sterilizing, and packaging.
2. The method for preparing metronidazole sodium chloride injection as claimed in claim 1, characterised in that it comprises the following steps:
(1) adding injection water accounting for 70-80% of the total volume of the prescription into a preparation tank, sequentially adding citric acid, anhydrous disodium hydrogen phosphate, metronidazole and sodium chloride in the prescription, stirring to dissolve, and supplementing the injection water to the total volume of the prescription, wherein the metronidazole is purer;
(2) stirring uniformly, sampling and detecting;
(3) filtering, bottling, sterilizing, and packaging.
3. The method for preparing metronidazole sodium chloride injection as claimed in claim 2, characterized in that: the weight ratio of the citric acid to the anhydrous disodium hydrogen phosphate to the metronidazole to the sodium chloride is 0.024-0.026:0.045-0.050:0.5: 0.8.
4. The method for preparing metronidazole sodium chloride injection as claimed in claim 2, characterized in that: the weight ratio of the citric acid to the anhydrous disodium hydrogen phosphate to the metronidazole to the sodium chloride is 0.024:0.045:0.5: 0.8.
5. The method for preparing metronidazole sodium chloride injection as claimed in claim 2, characterized in that: the weight ratio of the citric acid to the anhydrous disodium hydrogen phosphate to the metronidazole to the sodium chloride is 0.026:0.050:0.5: 0.8.
6. The method for preparing metronidazole sodium chloride injection as claimed in any of claims 1 to 5, wherein: the sterilization condition in the step (3) is sterilization at a temperature of 121 ℃ for 12 min.
7. The method for preparing metronidazole sodium chloride injection as claimed in any of claims 1 to 5, wherein: the PH value of the injection after the uniform stirring in the step (2) is 4.5-7.0.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110465351.XA CN113181113A (en) | 2021-04-28 | 2021-04-28 | Preparation method of metronidazole sodium chloride injection |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110465351.XA CN113181113A (en) | 2021-04-28 | 2021-04-28 | Preparation method of metronidazole sodium chloride injection |
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| CN113181113A true CN113181113A (en) | 2021-07-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN202110465351.XA Withdrawn CN113181113A (en) | 2021-04-28 | 2021-04-28 | Preparation method of metronidazole sodium chloride injection |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090017105A1 (en) * | 2007-03-19 | 2009-01-15 | Dhiraj Khattar | Proliposomal and liposomal compositions of poorly water soluble drugs |
| CN109431994A (en) * | 2018-12-20 | 2019-03-08 | 江西润泽药业有限公司 | Metronidazole injection and its preparation method and application |
| CN109432123A (en) * | 2018-11-23 | 2019-03-08 | 济南康和医药科技有限公司 | A kind of compound electrolyte glucose injection and preparation method thereof |
| CN110314133A (en) * | 2019-06-28 | 2019-10-11 | 石家庄四药有限公司 | A kind of metronidazole injection and preparation method thereof |
| WO2020221652A1 (en) * | 2019-04-28 | 2020-11-05 | Reponex Pharmaceuticals A/S | Composition for the intraperitoneal treatment of secondary bacterial peritonitis with reduction of complications |
| CN112137955A (en) * | 2020-11-05 | 2020-12-29 | 江苏豪森药业集团有限公司 | Morpholine ornidazole injection and preparation method thereof |
| CN113230208A (en) * | 2021-04-28 | 2021-08-10 | 四川科伦药业股份有限公司 | Fluconazole sodium chloride injection and preparation method thereof |
-
2021
- 2021-04-28 CN CN202110465351.XA patent/CN113181113A/en not_active Withdrawn
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090017105A1 (en) * | 2007-03-19 | 2009-01-15 | Dhiraj Khattar | Proliposomal and liposomal compositions of poorly water soluble drugs |
| CN109432123A (en) * | 2018-11-23 | 2019-03-08 | 济南康和医药科技有限公司 | A kind of compound electrolyte glucose injection and preparation method thereof |
| CN109431994A (en) * | 2018-12-20 | 2019-03-08 | 江西润泽药业有限公司 | Metronidazole injection and its preparation method and application |
| WO2020221652A1 (en) * | 2019-04-28 | 2020-11-05 | Reponex Pharmaceuticals A/S | Composition for the intraperitoneal treatment of secondary bacterial peritonitis with reduction of complications |
| CN110314133A (en) * | 2019-06-28 | 2019-10-11 | 石家庄四药有限公司 | A kind of metronidazole injection and preparation method thereof |
| CN112137955A (en) * | 2020-11-05 | 2020-12-29 | 江苏豪森药业集团有限公司 | Morpholine ornidazole injection and preparation method thereof |
| CN113230208A (en) * | 2021-04-28 | 2021-08-10 | 四川科伦药业股份有限公司 | Fluconazole sodium chloride injection and preparation method thereof |
Non-Patent Citations (2)
| Title |
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| 詹顺江，等: "利用正交试验法制订甲硝唑注射液配制工艺", 《海峡药学》 * |
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Application publication date: 20210730 |