CN113797165A - Ornidazole injection - Google Patents
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- CN113797165A CN113797165A CN202111159778.3A CN202111159778A CN113797165A CN 113797165 A CN113797165 A CN 113797165A CN 202111159778 A CN202111159778 A CN 202111159778A CN 113797165 A CN113797165 A CN 113797165A
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- 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
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- 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
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- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- 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
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- 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
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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
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- 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
- A61P31/04—Antibacterial agents
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Abstract
The invention relates to an ornidazole injection. The ornidazole injection comprises ornidazole, glycerol, ethanol and water, and the pH value of the ornidazole injection is adjusted by using a citric acid-disodium hydrogen phosphate buffer solution. The ornidazole injection has the pH value within the range of human body tolerable intravenous administration, so that adverse reactions such as administration pain and phlebitis are reduced, the administration compliance is improved, impurities are few, the purity is high, the high-temperature, high-humidity and low-temperature stability is excellent, the use of propylene glycol is avoided, and the high-safety ornidazole injection has excellent safety.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to an ornidazole injection.
Background
Ornidazole (ornidazole) is used for treating various infectious diseases caused by sensitive anaerobic bacteria such as Bacteroides fragilis, Bacteroides dirachtii, Bacteroides ovani, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Clostridium, Eubacterium, Peptococcus and Peptococcus, helicobacter tararii, Bacteroides melanogaster, Clostridium, CO2 Haemophilus, and Bacteroides gingivalis.
For the existing ornidazole injection, the influence of the pH value on the related substances of the ornidazole injection is very obvious, when the pH value of the ornidazole injection is more than 3.5, the related substances are increased more and exceed the content limit of a quality standard, and when the pH value is adjusted to be below 3.0, the increase of the related substances is relatively less, so the existing ornidazole injection can only be prepared under the condition of lower pH value. However, the pH value of the blood of a normal human body is 7.35-7.45, the pH value of the human body which can tolerate the transfusion is 4-9, and the ornidazole injection with low pH value exceeds the tolerance limit of the human body, so that the injection pain is easy to cause, and the adverse reactions such as phlebitis and the like are caused, and the compliance of a patient is poor. In addition, although the stability of the ornidazole injection can be improved by lowering the pH value, after high-temperature sterilization, the related substances of the ornidazole injection still rise, propylene glycol is also required to be added as a stabilizer, in order to improve the stability of the ornidazole injection, a larger amount of propylene glycol is required to be added as a stabilizer to keep the stability of the ornidazole injection, the dosage of the propylene glycol is higher and even up to 30%, however, the propylene glycol has a larger side effect as a stabilizer, easily causes the side effect which is not tolerated by human bodies, and as an injection solvent, the propylene glycol also has a certain stimulation effect, and increases the administration risk.
In order to improve the stability of the ornidazole injection, ethanol is often used as a pure solvent in the existing ornidazole injection, however, the ethanol is a volatile, flammable and explosive solvent, and the ethanol is used as the pure solvent, so that the requirements on preparation equipment and conditions of the ornidazole injection are high, the preparation cost of the ornidazole injection is increased, and the danger of flammability, explosiveness and the like is easily caused.
Research on the existing ornidazole injection finds that the ornidazole injection has poor stability under low temperature (such as-10 ℃ to 10 ℃) and is easy to have the problem of exceeding the standard of insoluble particles.
Therefore, there is a need in the art to develop an ornidazole injection capable of reducing adverse reactions such as administration pain and phlebitis and improving stability, thereby improving administration compliance and safety of the ornidazole injection.
Disclosure of Invention
The invention aims to provide the ornidazole injection which can reduce adverse reactions such as administration pain, phlebitis and the like and improve the stability, thereby improving the administration compliance and the safety of the ornidazole injection.
The invention provides an ornidazole injection, which comprises the following components:
preferably, the ornidazole injection comprises the following components:
preferably, the ornidazole injection comprises the following components:
preferably, the ornidazole injection comprises the following components:
preferably, the ornidazole injection comprises the following components:
preferably, the ornidazole injection comprises the following components:
preferably, the ornidazole injection comprises the following components:
preferably, the ornidazole injection comprises the following components:
preferably, the water comprises water for injection.
Preferably, the citric acid-disodium hydrogen phosphate buffer comprises citric acid, disodium hydrogen phosphate and water.
Preferably, the pH of the citric acid-disodium hydrogen phosphate buffer is 3.6-3.9, preferably 3.7-3.9, more preferably 3.75-3.80.
Preferably, the molar ratio of the citric acid to the disodium hydrogen phosphate is (0.5-1.5): (0.5-1.5), preferably (0.8-1.2): (0.8-1.2), preferably 1: 1.
Preferably, in the citric acid-disodium hydrogen phosphate buffer, the molar/volume ratio (mmol: ml) of the citric acid to the water is 1:25-40, preferably 1:30-35, more preferably 1: 32-35.
Preferably, the citric acid-disodium hydrogen phosphate buffer has a molar/volume ratio (mmol: ml) of the disodium hydrogen phosphate to the water of 1:25-40, preferably 1:30-35, more preferably 1: 32-35.
Preferably, the citric acid-disodium hydrogen phosphate buffer solution is prepared by the following method: mixing citric acid, disodium hydrogen phosphate and water to obtain a citric acid-disodium hydrogen phosphate buffer solution.
Preferably, the citric acid-disodium hydrogen phosphate buffer solution is prepared by the following method: 14-16mmol of citric acid and 14-16mmol of disodium hydrogen phosphate are dissolved in 490-510ml of water to obtain a citric acid-disodium hydrogen phosphate buffer solution.
In a second aspect of the present invention, there is provided a method for preparing the ornidazole injection according to the first aspect of the present invention, said method comprising the steps of:
(1) mixing the prescription amount of glycerol, the prescription amount of ethanol and the prescription amount of water to obtain a solvent;
(2) adding ornidazole with the prescription amount into the solvent, and stirring and uniformly mixing to obtain liquid medicine;
(3) and (3) adjusting the pH value of the liquid medicine by using a citric acid-disodium hydrogen phosphate buffer solution, filtering and sterilizing to obtain the ornidazole injection.
Preferably, in the step (2), the temperature for mixing is 35-45 ℃, preferably 38-42 ℃.
Preferably, the step (2) comprises the steps of:
adding ornidazole with the amount of the prescription into the solvent with the amount of 50-70%, stirring and mixing uniformly, adding the rest amount of the solvent, and stirring and mixing uniformly to obtain the liquid medicine.
Preferably, the step (2) comprises the steps of:
adding ornidazole with the amount of the prescription into the solvent with the amount of 55-65%, stirring and mixing uniformly, adding the rest amount of the solvent, and stirring and mixing uniformly to obtain the liquid medicine.
Preferably, the step (2) comprises the steps of:
adding ornidazole in a prescription amount into the solvent in an amount of 50-70%, stirring and dissolving at 35-45 ℃, adding the rest amount of the solvent, and stirring and uniformly mixing at 35-45 ℃ to obtain liquid medicine.
Preferably, the step (2) comprises the steps of:
adding ornidazole in the amount of the prescription into the solvent in the amount of 55-65%, stirring and dissolving at 38-42 ℃, adding the rest amount of the solvent, and stirring and uniformly mixing at 38-42 ℃ to obtain liquid medicine.
Preferably, in the step (3), the pH of the liquid medicine is adjusted to 4.5-6.5, preferably 5.0-6.0, preferably 5.2-5.6, preferably 5.4, by using a citric acid-disodium hydrogen phosphate buffer solution.
Preferably, in the step (3), the filtration comprises microfiltration.
Preferably, the microfiltration membrane comprises a 0.1-0.5 μm microfiltration membrane.
Preferably, the microfiltration membrane comprises a 0.1-0.3 μm microfiltration membrane.
Preferably, the microfiltration membrane comprises a 0.22 μm microfiltration membrane.
Preferably, in the step (3), the temperature for sterilization is 100-.
Preferably, in the step (3), the sterilization time is 20-40min, preferably 25-35min, and more preferably 30 min.
Preferably, in the step (3), after filtration, the mixture is packaged in ampoules and then sterilized.
In a third aspect of the present invention, there is provided a use of the ornidazole injection according to the first aspect of the present invention in the preparation of a medicament for preventing and/or treating infectious diseases caused by microorganisms selected from the group consisting of: bacteroides fragilis, bacteroides diesei, bacteroides ovatus, bacteroides thetaiotaomicron, bacteroides vulgatus, clostridium difficile, eubacterium, enterococcus and streptococcus digesta, helicobacter tarmitis, bacteroides melanoides, clostridium, CO2 vibrio bacteriovorus, gingival bacteroides, or combinations thereof.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments.
Detailed Description
The invention discloses an ornidazole injection, which comprises ornidazole, glycerol, ethanol and water, and the pH value of the ornidazole injection is adjusted by using a citric acid-disodium hydrogen phosphate buffer solution. The ornidazole injection has the pH value within the range of human body tolerable intravenous administration, so that adverse reactions such as administration pain and phlebitis are reduced, the administration compliance is improved, impurities are few, the purity is high, the high-temperature, high-humidity and low-temperature stability is excellent, the use of propylene glycol is avoided, and the high-safety ornidazole injection has excellent safety.
Term(s) for
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
As used herein, the terms "comprises," "comprising," "includes," "including," and "including" are used interchangeably and include not only closed-form definitions, but also semi-closed and open-form definitions. In other words, the term includes "consisting of … …", "consisting essentially of … …".
Ornidazole injection
The ornidazole injection has the pH value within the range of human body tolerable intravenous administration, so that adverse reactions such as administration pain and phlebitis are reduced, the administration compliance is improved, impurities are few, the purity is high, the high-temperature, high-humidity and low-temperature stability is excellent, the use of propylene glycol is avoided, and the high-safety ornidazole injection has excellent safety.
In a preferred embodiment of the present invention, the ornidazole injection solution comprises the following components:
in a preferred embodiment of the present invention, the ornidazole injection solution comprises the following components:
in a preferred embodiment of the present invention, the ornidazole injection solution comprises the following components:
in a preferred embodiment of the present invention, the ornidazole injection solution comprises the following components:
in a preferred embodiment of the present invention, the ornidazole injection solution comprises the following components:
in a preferred embodiment of the present invention, the ornidazole injection solution comprises the following components:
in a preferred embodiment of the present invention, the ornidazole injection solution comprises the following components:
in a preferred embodiment of the present invention, the ornidazole injection solution comprises the following components:
in a preferred embodiment of the present invention, the water comprises water for injection.
In a preferred embodiment of the present invention, the citric acid-disodium hydrogen phosphate buffer comprises citric acid, disodium hydrogen phosphate and water.
Preferably, the pH of the citric acid-disodium hydrogen phosphate buffer is 3.6-3.9, preferably 3.7-3.9, more preferably 3.75-3.80.
Preferably, the molar ratio of the citric acid to the disodium hydrogen phosphate is (0.5-1.5): (0.5-1.5), preferably (0.8-1.2): (0.8-1.2), preferably 1: 1.
Preferably, in the citric acid-disodium hydrogen phosphate buffer, the molar/volume ratio (mmol: ml) of the citric acid to the water is 1:25-40, preferably 1:30-35, and more preferably 1: 32-35.
Preferably, the citric acid-disodium hydrogen phosphate buffer has a molar/volume ratio (mmol: ml) of the disodium hydrogen phosphate to the water of 1:25-40, preferably 1:30-35, more preferably 1: 32-35.
Preferably, the citric acid-disodium hydrogen phosphate buffer solution is prepared by the following method: mixing citric acid, disodium hydrogen phosphate and water to obtain a citric acid-disodium hydrogen phosphate buffer solution.
Typically, the citric acid-disodium hydrogen phosphate buffer is prepared by the following method: 14-16mmol of citric acid and 14-16mmol of disodium hydrogen phosphate are dissolved in 490-510ml of water to obtain a citric acid-disodium hydrogen phosphate buffer solution.
Preparation method
The invention also provides a preparation method of the ornidazole injection.
In a preferred embodiment of the present invention, the preparation method of the ornidazole injection comprises the following steps:
(1) mixing the prescription amount of glycerol, the prescription amount of ethanol and the prescription amount of water to obtain a solvent;
(2) adding ornidazole with the prescription amount into the solvent, and stirring and uniformly mixing to obtain liquid medicine;
(3) and (3) adjusting the pH value of the liquid medicine by using a citric acid-disodium hydrogen phosphate buffer solution, filtering and sterilizing to obtain the ornidazole injection.
Preferably, in the step (2), the temperature for mixing is 35-45 ℃, preferably 38-42 ℃.
Preferably, the step (2) comprises the steps of:
adding ornidazole with the amount of the prescription into the solvent with the amount of 50-70%, stirring and mixing uniformly, adding the rest amount of the solvent, and stirring and mixing uniformly to obtain the liquid medicine.
Preferably, the step (2) comprises the steps of:
adding ornidazole with the amount of the prescription into the solvent with the amount of 55-65%, stirring and mixing uniformly, adding the rest amount of the solvent, and stirring and mixing uniformly to obtain the liquid medicine.
Preferably, the step (2) comprises the steps of:
adding ornidazole in a prescription amount into the solvent in an amount of 50-70%, stirring and dissolving at 35-45 ℃, adding the rest amount of the solvent, and stirring and uniformly mixing at 35-45 ℃ to obtain liquid medicine.
Preferably, the step (2) comprises the steps of:
adding ornidazole in the amount of the prescription into the solvent in the amount of 55-65%, stirring and dissolving at 38-42 ℃, adding the rest amount of the solvent, and stirring and uniformly mixing at 38-42 ℃ to obtain liquid medicine.
Preferably, in the step (3), the pH of the liquid medicine is adjusted to 4.5-6.5, preferably 5.0-6.0, preferably 5.2-5.6, preferably 5.4, by using a citric acid-disodium hydrogen phosphate buffer solution.
Preferably, in the step (3), the filtration comprises microfiltration.
Preferably, the microfiltration membrane comprises a 0.1-0.5 μm microfiltration membrane.
Preferably, the microfiltration membrane comprises a 0.1-0.3 μm microfiltration membrane.
Preferably, the microfiltration membrane comprises a 0.22 μm microfiltration membrane.
Preferably, in the step (3), the temperature for sterilization is 100-.
Preferably, in the step (3), the sterilization time is 20-40min, preferably 25-35min, and more preferably 30 min.
Preferably, in the step (3), after filtration, the mixture is packaged in ampoules and then sterilized.
Use of
The invention also provides an application of the ornidazole injection, which is used for preparing a medicament for preventing and/or treating infectious diseases caused by microorganisms selected from the following groups: bacteroides fragilis, bacteroides diesei, bacteroides ovatus, bacteroides thetaiotaomicron, bacteroides vulgatus, clostridium difficile, eubacterium, enterococcus and streptococcus digesta, helicobacter tarmitis, bacteroides melanoides, clostridium, CO2 vibrio bacteriovorus, gingival bacteroides, or combinations thereof.
The main advantages of the invention include:
1. the pH value of the ornidazole injection developed by the invention is in the range of human body tolerable intravenous administration, thereby reducing adverse reactions such as administration pain, phlebitis and the like and improving administration compliance.
2. The ornidazole injection developed by the invention has the advantages of less impurities, high purity and excellent stability, and avoids the use of propylene glycol, thereby having excellent safety.
3. The ornidazole injection developed by the invention has excellent high-temperature, high-humidity and low-temperature stability, so that the ornidazole injection is convenient to store and transport and has wide application environment range (such as hot and cold regions).
4. The ornidazole injection developed by the invention has the advantages of simple prescription and preparation process, low cost, safety, reliability and suitability for industrial production.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental methods in the following examples, which are not specified under specific conditions, are generally performed under conventional conditions.
Example 1
This example 1 provides an ornidazole injection and a method for preparing the same
1. The prescription of ornidazole injection is shown in the following table 1:
TABLE 1 Ornidazole injection prescription
| Components | Dosage of |
| Ornidazole | 10g |
| Glycerol | 2ml |
| Ethanol | 28ml |
| Water for injection | 30ml |
| Adjusting pH to with citric acid-disodium hydrogen phosphate buffer | 5.4 |
The citric acid-disodium hydrogen phosphate buffer solution is prepared as follows: 15mmol of citric acid and 15mmol of disodium hydrogen phosphate were dissolved in 500ml of water for injection to obtain a citric acid-disodium hydrogen phosphate buffer.
2. The preparation method of the ornidazole injection comprises the following steps:
(1) preparing a solvent: mixing the prescription amount of glycerol, the prescription amount of ethanol and the prescription amount of water for injection to obtain the solvent.
(2) Adding ornidazole in the amount of the prescription into solvent in the amount of 60%, stirring and dissolving at 40 ℃, adding the solvent in the amount of the remaining 40%, and stirring and uniformly mixing at 40 ℃ to obtain liquid medicine.
(3) Adjusting pH of the medicinal liquid to 5.4 with citric acid-disodium hydrogen phosphate buffer solution, filtering with 0.22 μm microporous membrane, packaging in ampoule bottle, and sterilizing at 121 deg.C for 30min to obtain ornidazole injection.
Comparative example 1
The comparative example 1 provides an ornidazole injection and a preparation method thereof
1. The prescription of ornidazole injection is shown in the following table 2:
TABLE 2 Ornidazole injection prescription
| Components | Dosage of |
| Ornidazole | 10g |
| Ethanol | 30ml |
| Water for injection | 30ml |
| Adjusting pH to with citric acid-disodium hydrogen phosphate buffer | 5.4 |
The citric acid-disodium hydrogen phosphate buffer solution is prepared as follows: 15mmol of citric acid and 15mmol of disodium hydrogen phosphate were dissolved in 500ml of water for injection to obtain a citric acid-disodium hydrogen phosphate buffer.
2. The preparation method of the ornidazole injection comprises the following steps:
(1) preparing a solvent: mixing the prescription amount of ethanol and the prescription amount of water for injection to obtain a solvent.
(2) Adding ornidazole in the amount of the prescription into solvent in the amount of 60%, stirring and dissolving at 40 ℃, adding the solvent in the amount of the remaining 40%, and stirring and uniformly mixing at 40 ℃ to obtain liquid medicine.
(3) Adjusting pH of the medicinal liquid to 5.4 with citric acid-disodium hydrogen phosphate buffer solution, filtering with 0.22 μm microporous membrane, packaging in ampoule bottle, and sterilizing at 121 deg.C for 30min to obtain ornidazole injection.
Comparative example 2
The comparative example 2 provides an ornidazole injection and a preparation method thereof
1. The prescription of ornidazole injection is shown in table 3 below:
TABLE 3 Ornidazole injection prescription
| Components | Dosage of |
| Ornidazole | 10g |
| Glycerol | 2ml |
| Ethanol | 28ml |
| Phosphate buffer | 30ml |
Wherein, the phosphate buffer solution is prepared as follows: 15mmol of sodium dihydrogen phosphate was dissolved in 500ml of water for injection to obtain a phosphate buffer.
2. The preparation method of the ornidazole injection comprises the following steps:
(1) preparing a solvent: mixing the prescription amount of glycerol, the prescription amount of ethanol and the prescription amount of phosphate buffer solution to obtain the solvent.
(2) Adding ornidazole in the amount of the prescription into solvent in the amount of 60%, stirring and dissolving at 40 ℃, adding the solvent in the amount of the remaining 40%, and stirring and uniformly mixing at 40 ℃ to obtain liquid medicine.
(3) Filtering the medicinal liquid with 0.22 μm microporous membrane, packaging in ampoule bottle, and sterilizing at 121 deg.C for 30min to obtain ornidazole injection.
Stability survey
1. Accelerated stability review
According to the guidelines of the stability test of pharmaceutical preparations in Chinese pharmacopoeia, accelerated stability test is performed under the conditions of 40 + -2 ℃ and 75 + -5% relative humidity RH, the stability of the ornidazole injection prepared in example 1 after preparation (0 day), 1, 3 and 6 months is accelerated, impurities and contents are measured by HPLC, and the results are shown in Table 4:
TABLE 4 accelerated stability test results of ornidazole injection prepared in example 1 at 40 + -2 deg.C and RH 75 + -5%
Remarking: before sterilization, the intermediate liquid medicine is sterilized at 121 ℃ in the preparation process.
As can be seen from table 4, the ornidazole injection prepared in example 1 has excellent accelerated stability, meets the quality requirements, and is convenient to store and transport.
2. Investigation of Low temperature stability
The stability of the ornidazole injections prepared in example 1 and comparative examples 1-2 at low temperature of 4 ℃ was examined. The specific determination method comprises the following steps: the ornidazole injections prepared in example 1 and comparative examples 1-2 were examined at 4 deg.c and RH 75 ± 5% for 1, 3 and 6 months, and then examined for insoluble particles according to the insoluble particle examination method in chinese pharmacopoeia, and the results are shown in the following table 5:
TABLE 5 stability test results of ornidazole injections prepared in example 1 and comparative examples 1-2 at 4 deg.C and RH 75 + -5%
As can be seen from table 5, the ornidazole injection prepared in example 1 has excellent low-temperature stability and meets the quality requirements.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.
Claims (10)
1. The ornidazole injection is characterized by comprising the following components:
2. the ornidazole injection as claimed in claim 1, wherein the ornidazole injection comprises the following components:
3. the ornidazole injection as claimed in claim 1, wherein the ornidazole injection comprises the following components:
4. the ornidazole injection as claimed in claim 1, wherein the ornidazole injection comprises the following components:
5. the ornidazole injection as claimed in claim 1, wherein the ornidazole injection comprises the following components:
6. the ornidazole injection as claimed in claim 1, wherein the ornidazole injection comprises the following components:
7. the ornidazole injection of claim 1 wherein the citric acid-disodium phosphate buffer comprises citric acid, disodium phosphate and water.
8. The ornidazole injection as claimed in claim 1, wherein the citric acid-disodium hydrogen phosphate buffer is prepared by the following method: 14-16mmol of citric acid and 14-16mmol of disodium hydrogen phosphate are dissolved in 490-510ml of water to obtain a citric acid-disodium hydrogen phosphate buffer solution.
9. A method of preparing the ornidazole injection of claim 1, characterised in that it comprises the steps of:
(1) mixing the prescription amount of glycerol, the prescription amount of ethanol and the prescription amount of water to obtain a solvent;
(2) adding ornidazole with the prescription amount into the solvent, and stirring and uniformly mixing to obtain liquid medicine;
(3) and (3) adjusting the pH value of the liquid medicine by using a citric acid-disodium hydrogen phosphate buffer solution, filtering and sterilizing to obtain the ornidazole injection.
10. Use of the ornidazole injection according to claim 1, in the preparation of a medicament for the prevention and/or treatment of infectious diseases caused by microorganisms chosen from the group consisting of: bacteroides fragilis, bacteroides diesei, bacteroides ovatus, bacteroides thetaiotaomicron, bacteroides vulgatus, clostridium difficile, eubacterium, enterococcus and streptococcus digesta, helicobacter tarmitis, bacteroides melanoides, clostridium, CO2 vibrio bacteriovorus, gingival bacteroides, or combinations thereof.
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| CN202111159778.3A CN113797165A (en) | 2021-09-30 | 2021-09-30 | Ornidazole injection |
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|---|---|---|---|
| CN202111159778.3A CN113797165A (en) | 2021-09-30 | 2021-09-30 | Ornidazole injection |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1820748A (en) * | 2005-12-19 | 2006-08-23 | 广东先强药业有限公司 | Levo-ornidazole freeze-dried powder injection |
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