CN114028345B - Aspoxicillin freeze-dried agent for injection and preparation process thereof - Google Patents
Aspoxicillin freeze-dried agent for injection and preparation process thereof Download PDFInfo
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- CN114028345B CN114028345B CN202111366438.8A CN202111366438A CN114028345B CN 114028345 B CN114028345 B CN 114028345B CN 202111366438 A CN202111366438 A CN 202111366438A CN 114028345 B CN114028345 B CN 114028345B
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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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
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
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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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
- A61K9/0012—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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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
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention provides a preparation process of aspoxicillin freeze-dried preparation for injection, which takes 45-55 parts of aspoxicillin, 1-2 parts of mannitol, 0.2-0.4 part of sodium glutamate and 250-300 parts of water for injection as raw materials in parts by weight, aspoxicillin liquid medicine is prepared by step mixing, and the aspoxicillin liquid medicine is prepared into the aspoxicillin freeze-dried preparation for injection which is stable at high temperature and has good redissolution effect through three stages of prefreezing, sublimating and drying.
Description
Technical Field
The invention relates to the field of aspoxicillin, and in particular relates to an aspoxicillin freeze-dried preparation for injection and a preparation process thereof.
Background
Aspoxicillin is a semi-synthetic penicillin broad-spectrum antibiotic, and has a strong antibacterial effect, and the antibacterial spectrum comprises gram-positive bacteria such as staphylococcus, streptococcus and pneumococcus, and gram-negative bacteria such as escherichia coli, influenza bacillus and anaerobic bacteroides. The traditional Chinese medicine composition is clinically used for septicemia, endocarditis, respiratory tract infection, biliary tract infection, peritonitis and the like caused by sensitive bacteria.
The aspoxicillin is not stable in a solution state and is suitable for being prepared into a freeze-dried preparation for use, and CN103467492B is an aspoxicillin compound, a pharmaceutical composition, a preparation and a preparation method thereof use the aspoxicillin as a main drug, and a pharmaceutical adjuvant is at least one selected from an excipient, a pH value regulator, a cosolvent and an osmotic pressure regulator; the excipient is at least one of lactose, sorbitol, xylitol, dextran, mannitol and sodium chloride; the alkali in the pH regulator is at least one selected from potassium hydroxide, sodium bicarbonate and sodium carbonate; the acid is at least one selected from hydrochloric acid, phosphoric acid and sulfuric acid. Aspoxicillin is sensitive to high temperature, new impurities are generated in a high-temperature environment, and therefore a preparation process is needed for preparing aspoxicillin freeze-dried preparation with high stability in the high-temperature environment, and product loss is reduced in the preparation process.
Disclosure of Invention
Therefore, the invention provides an aspoxicillin freeze-dried agent for injection and a preparation process thereof, which improve the stability of aspoxicillin in a high-temperature environment and reduce the loss of products.
The technical scheme of the invention is realized as follows:
an aspoxicillin freeze-dried agent for injection comprises the following raw materials in parts by weight: 45-55 parts of aspoxicillin, 1-2 parts of mannitol, 0.2-0.4 part of sodium glutamate and 250-300 parts of water for injection.
Further, the preparation process of aspoxicillin for injection comprises the following steps:
s1, adding mannitol and sodium glutamate into water for injection, and stirring to prepare a solution 1;
s2, adding aspoxicillin into the solution 1, and stirring to obtain a solution 2;
s3, adjusting the pH value of the solution 2 to 7.3-7.7 by using a sodium citrate solution to prepare a solution 3, and filtering to prepare aspoxicillin liquid medicine;
s4, sub-packaging aspoxicillin liquid medicine in injection bottles made of low borosilicate glass tubes, regulating the temperature of a partition plate to be-15 to-20 ℃, placing the sub-packaged aspoxicillin on the partition plate, cooling to-35 to-38 ℃, keeping the temperature of the aspoxicillin liquid medicine to be-30 ℃, and preserving the temperature for 1.5 to 2.5 hours to obtain a pre-frozen aspoxicillin product;
s5, adjusting the vacuum degree to be 5-7pa, heating to 0-4 ℃, and preserving heat for 15-25h when the temperature of the aspoxicillin product reaches-2 ℃ to obtain a sublimed aspoxicillin product;
s6, adjusting the vacuum degree to 8-10pa, heating to 35-37 ℃, and preserving the temperature for 4-6h when the temperature of the aspoxicillin product reaches 30 ℃ to obtain the aspoxicillin for injection.
Further, the temperature of the solution 1, the solution 2, the solution 3 and the aspoxicillin liquid medicine is 2-4 ℃.
Further, in the step S3, the filtering is performed by stirring and adsorbing for 15-25min by using medicinal carbon, and the using mass of the medicinal carbon is 0.10% of the total mass of the solution 4.
Further, in the step S4, the aspoxicillin liquid medicine low borosilicate glass tube injection bottle is subpackaged, the temperature of the partition plate is controlled to be-15 to-20 ℃, the subpackaged aspoxicillin is placed on the partition plate, and the temperature is reduced to-35 to-38 ℃ at the rate of 1-2 ℃/min.
Further, in step S5, the temperature is raised to 0-4 ℃ at a rate of 0.4-0.6 ℃/min.
Further, in step S6, the temperature is raised to 35-37 ℃ at a rate of 0.2-0.4 ℃/min.
Further, in the step S2, the stirring speed is 180-220r/min, and the stirring time is 20-30min.
Further, in the step S3, the concentration of the sodium citrate solution is 0.1-0.2 mol/L.
Compared with the prior art, the invention has the beneficial effects that:
according to the invention, 45-55 parts of aspoxicillin, 1-2 parts of mannitol, 0.2-0.4 part of sodium glutamate and 250-300 parts of water for injection are taken as raw materials to prepare an aspoxicillin freeze-drying agent for injection, the aspoxicillin is slightly dissolved in water, the aspoxicillin is compounded with auxiliary materials, and the solubility of the aspoxicillin freeze-drying agent is increased by means of adding alkali to form salt; in order to ensure that the aspoxicillin is qualified in appearance and the storage time is prolonged, mannitol is used as a support agent, the use amount of water for injection is determined according to the properties of raw materials and auxiliary materials, and the aspoxicillin freeze-dried preparation for injection with high stability and good dissolution effect is prepared.
The freeze-drying process improves the product quality and reduces the loss of finished products through reasonable temperature rising and reducing rates and temperature setting. In the pre-freezing process, the phenomena of non-uniform crystallization and product loss are easy to occur due to too fast temperature rise, and the sublimation effect is further deteriorated due to non-uniform crystallization; in the sublimation process, the temperature is raised too fast, so that the interior of aspoxicillin is heated unevenly and broken, and the moisture removing effect in the sublimation process is reduced.
Detailed Description
In order to better understand the technical content of the invention, specific examples are provided below to further illustrate the invention.
The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified.
The materials, reagents and the like used in the examples of the present invention are commercially available unless otherwise specified.
EXAMPLE 1 Process for the preparation of injectable aspoxicillin lyophilisate
(1) Weighing the following raw materials in parts by weight: 45 parts of aspoxicillin, 1 part of mannitol, 0.2 part of sodium glutamate and 250 parts of water for injection for later use.
(2) Adding mannitol and sodium glutamate into injectable water, stirring to obtain solution 1, and maintaining the temperature of solution 1 at 2 deg.C.
(3) Adding aspoxicillin into the solution 1, stirring for 20min at 180r/min to obtain a solution 2, and keeping the temperature of the solution 2 at 2 ℃.
(4) Adjusting pH of the solution 2 to 7.3 with 0.1mol/L sodium citrate solution to obtain solution 3, stirring and adsorbing the solution 3 with 0.10% (w/w) medicinal carbon for 15min to obtain aspoxicillin liquid, and maintaining the temperature of the aspoxicillin liquid at 2 deg.C.
(5) Subpackaging aspoxicillin liquid medicine by using a low borosilicate glass tube injection bottle, regulating the temperature of a partition plate to be-15 ℃, placing the subpackaged aspoxicillin on the partition plate, cooling to-35 ℃ at a cooling rate of 1 ℃/min, keeping the temperature of the aspoxicillin liquid medicine to be-30 ℃, and preserving the heat for 1.5 hours to prepare a pre-frozen aspoxicillin product;
(6) Adjusting the vacuum degree to 5pa, heating to 0 ℃ at the heating rate of 0.4 ℃/min, and keeping the temperature for 15h when the temperature of the aspoxicillin product reaches-2 ℃ to obtain a sublimed aspoxicillin product;
(7) Adjusting the vacuum degree to 8pa, heating to 35 ℃ at the heating rate of 0.2 ℃/min, and keeping the temperature for 4h when the temperature of the aspoxicillin product reaches 30 ℃ to prepare the aspoxicillin for injection.
EXAMPLE 2 preparation of aspoxicillin lyophilized formulation for injection
(1) Weighing the following raw materials in parts by weight: 55 parts of aspoxicillin, 2 parts of mannitol, 0.4 part of sodium glutamate and 300 parts of water for injection for later use.
(2) Adding mannitol and sodium glutamate into injectable water, stirring to obtain solution 1, and maintaining the temperature of solution 1 at 4 deg.C.
(3) Adding aspoxicillin into the solution 1, stirring at 220r/min for 30min to obtain solution 2, and maintaining the temperature of the solution 2 at 4 deg.C.
(4) Adjusting pH of the solution 2 to 7.7 with 0.2mol/L sodium citrate solution to obtain solution 3, stirring and adsorbing the solution 3 with 0.10% (w/w) medicinal carbon for 25min to obtain aspoxicillin liquid, and maintaining the temperature of the aspoxicillin liquid at 4 deg.C.
(5) Subpackaging aspoxicillin liquid medicine by using low borosilicate glass tube injection bottles, regulating the temperature of a partition plate to be-20 ℃, placing the subpackaged aspoxicillin on the partition plate, cooling to-38 ℃ at a cooling rate of 2 ℃/min, keeping the temperature of the aspoxicillin liquid medicine to be-30 ℃, and preserving the heat for 2.5 hours to prepare a pre-frozen aspoxicillin product.
(6) Adjusting the vacuum degree to 7pa, heating to 4 ℃ at the heating rate of 0.6 ℃/min, and keeping the temperature for 25h when the temperature of the aspoxicillin product reaches-2 ℃ to obtain the sublimated aspoxicillin product.
(7) Adjusting the vacuum degree to 10pa, heating to 37 ℃ at the heating rate of 0.4 ℃/min, and keeping the temperature for 6h when the temperature of the aspoxicillin product reaches 30 ℃, thereby obtaining the aspoxicillin for injection.
EXAMPLE 3 preparation of aspoxicillin lyophilized formulation for injection
(1) Weighing the following raw materials in parts by weight: 50 parts of aspoxicillin, 1.5 parts of mannitol, 0.3 part of sodium glutamate and 280 parts of water for injection for later use.
(2) Adding mannitol and sodium glutamate into injectable water, stirring to obtain solution 1, and maintaining the temperature of solution 1 at 3 deg.C.
(3) Adding aspoxicillin into the solution 1, stirring at 200r/min for 25min to obtain a solution 2, and keeping the temperature of the solution 2 at 3 ℃.
(4) Adjusting pH of the solution 2 to 7.5 with 0.15mol/L sodium citrate solution to obtain solution 3, stirring and adsorbing the solution 3 with 0.10% (w/w) medicinal carbon for 20min to obtain aspoxicillin liquid medicine, and maintaining the temperature of the aspoxicillin liquid medicine at 3 deg.C.
(5) Subpackaging aspoxicillin liquid medicine by using a low borosilicate glass tube injection bottle, regulating the temperature of a partition plate to be-17 ℃, placing the subpackaged aspoxicillin on the partition plate, cooling to-36.5 ℃ at a cooling rate of 1.5 ℃/min, keeping the temperature of the aspoxicillin liquid medicine to be-30 ℃ and preserving the heat for 2 hours to prepare a prefrozen aspoxicillin product;
(6) Adjusting the vacuum degree to 6pa, heating to 2 ℃ at the heating rate of 0.5 ℃/min, and keeping the temperature for 20h when the temperature of the aspoxicillin product reaches-2 ℃ to obtain a sublimed aspoxicillin product;
(7) Adjusting the vacuum degree to 9pa, heating to 36 ℃ at the heating rate of 0.3 ℃/min, and keeping the temperature for 5h when the temperature of the aspoxicillin product reaches 30 ℃ to prepare the aspoxicillin for injection.
Comparative example 1
On the basis of the example 3, the raw material components are adjusted, specifically: weighing the following raw materials in parts by weight: 50 parts of aspoxicillin, 1.5 parts of glucose, 0.3 part of sodium glutamate and 280 parts of water for injection for later use.
Comparative example 2
On the basis of the embodiment 3, the usage amount of the water for injection is adjusted, specifically: weighing the following raw materials in parts by weight: 50 parts of aspoxicillin, 1.5 parts of mannitol, 0.3 part of sodium glutamate and 360 parts of water for injection for later use.
Comparative example 3
On the basis of the embodiment 3, the cooling rate in the step (5) is adjusted, specifically: subpackaging aspoxicillin liquid medicine by using low borosilicate glass tube injection bottles, regulating the temperature of a partition plate to be-17 ℃, placing the subpackaged aspoxicillin on the partition plate, cooling to-36.5 ℃ at a cooling rate of 3 ℃/min, keeping the temperature of the aspoxicillin liquid medicine to be-30 ℃ and preserving the heat for 2 hours to prepare a pre-frozen aspoxicillin product.
Comparative example 4
On the basis of the embodiment 3, the temperature increase rate in the step (6) is adjusted, specifically: adjusting the vacuum degree to 6pa, heating to 2 ℃ at the heating rate of 2 ℃/min, and keeping the temperature for 20h when the temperature of the aspoxicillin product reaches 0 ℃, thereby obtaining the sublimed aspoxicillin product.
Comparative example 5
On the basis of the embodiment 3, the temperature increase rate in the step (7) is adjusted, specifically: adjusting the vacuum degree to 9pa, heating to 36 ℃ at the heating rate of 1 ℃/min, and keeping the temperature for 5h when the temperature of the aspoxicillin product reaches 30 ℃, thereby obtaining the aspoxicillin for injection.
Test example 1
Using the preparation processes of examples 1-3 and comparative examples 1-5 to prepare 100 bottles of aspoxicillin freeze-dried preparations for injection respectively, and the prepared aspoxicillin freeze-dried preparations for injection are subjected to appearance property, pH value, content and related substance (total impurity) detection and influence factor test (high temperature): storing at 60 deg.C for 10 days, and testing appearance, pH value, content and related substances (total impurities). The content and related substances are detected according to a detection method in aspoxicillin quality research in Anhui medicine.
Yield (%) = (total amount-number of damage)/total amount × 100
The breakage is the case of bottle washing and breakage.
TABLE 1 detection results of appearance, pH, content, related substances (total impurities) and yield of aspoxicillin lyophilized preparation for injection
Experimental results show that the aspoxicillin freeze-dried preparation for injection prepared by combining the raw materials and the preparation process has the advantages of good appearance, low breakage rate, no obvious increase or decrease of the content and low impurity content. Comparative example 1 adjusting component raw materials, using glucose to easily decompose under alkaline conditions to generate 5-hydroxy furfural, affecting the quality of injection; comparative example 2 the use amount of the water for injection is adjusted, so that the concentration of the liquid medicine is changed, the pre-freezing effect is reduced, and the quality of the finished product is influenced; the comparative example 3 adjusts the cooling rate in the pre-freezing process, and the temperature difference inside the liquid medicine is too large due to too fast cooling, so that not only crystallization nonuniformity is easy to occur, the bottom of a finished product is shrunk and layered, but also bottle cracking is easy to occur; comparative example 4 the heating rate is adjusted, the collapse of the middle of the product is caused by the drying shrinkage of the product, and the sublimation effect is poor; comparative example 5 the rate of temperature rise was adjusted, resulting in non-uniform evaporation of water and slightly lumping of the finished product.
TABLE 2 high temperature 10 days influencing factor test results
The experimental result shows that the raw materials and the preparation process are combined, the prepared aspoxicillin freeze-dried preparation for injection is stored for 10 days at high temperature (60 ℃), the content reduction range is less than 1%, the total impurity growth range is less than 0.2%, the requirements are met, the formula of the invention is reasonably combined with the preparation process, and the prepared aspoxicillin freeze-dried preparation for injection has stable and controllable quality.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (5)
1. An aspoxicillin freeze-dried agent for injection is characterized by comprising the following raw materials in parts by weight: 45-55 parts of aspoxicillin, 1-2 parts of mannitol, 0.2-0.4 part of sodium glutamate and 250-300 parts of water for injection;
the preparation method comprises the following steps:
s1, adding mannitol and sodium glutamate into water for injection, and stirring to obtain a solution 1;
s2, adding aspoxicillin into the solution 1, and stirring to obtain a solution 2;
s3, adjusting the pH value of the solution 2 to 7.3-7.7 by using a sodium citrate solution to prepare a solution 3, and filtering to prepare aspoxicillin liquid medicine;
s4, sub-packaging the aspoxicillin liquid medicine in a low borosilicate glass tube injection bottle, regulating the temperature of a partition board to be minus 15 to minus 20 ℃, placing the sub-packaged aspoxicillin on the partition board, cooling to be minus 35 to minus 38 ℃ at a cooling rate of 1 to 2 ℃/min, keeping the temperature of the aspoxicillin liquid medicine to be minus 30 ℃, and preserving the heat for 1.5 to 2.5 hours to prepare a pre-frozen aspoxicillin product;
s5, adjusting the vacuum degree to 5-7pa, heating to 0~4 ℃ at the heating rate of 0.4-0.6 ℃/min, and preserving heat for 15-25h when the temperature of the aspoxicillin product reaches-2 ℃ to obtain the sublimed aspoxicillin product;
s6, adjusting the vacuum degree to be 8-10pa, heating to 35-37 ℃ at the heating rate of 0.2-0.4 ℃/min, and keeping the temperature for 4-6h when the temperature of the aspoxicillin product reaches 30 ℃, thereby preparing the aspoxicillin for injection.
2. The process for preparing aspoxicillin lyophilized formulation for injection as claimed in claim 1, wherein the temperature of solution 1, solution 2, solution 3 and aspoxicillin liquid is 2-4 ℃.
3. The preparation process of aspoxicillin lyophilized formulation for injection of claim 1, wherein in step S3, the filtration is performed by stirring and adsorbing with medicinal charcoal for 15-25min, and the use mass of the medicinal charcoal is 0.10% of the total mass of solution 4.
4. The process for preparing aspoxicillin lyophilized formulation for injection as claimed in claim 1, wherein in step S2, the stirring speed is 180-220r/min, and the stirring time is 20-30min.
5. The preparation process of aspoxicillin lyophilized formulation for injection of claim 1, wherein in step S3, the concentration of the sodium citrate solution is 0.1-0.2 mol/L.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998022114A1 (en) * | 1996-11-15 | 1998-05-28 | Dumex-Alpharma A/S | A method for promoting tissue repair |
| WO2004066910A2 (en) * | 2003-01-31 | 2004-08-12 | Glenmark Pharmaceuticals Ltd. | Controlled release modifying complex and pharmaceutical compositions thereof |
| CN101862299A (en) * | 2009-04-17 | 2010-10-20 | 北京本草天源药物研究院 | Preparation method of aspoxicillin freeze-dried powder injection |
| CN103467492A (en) * | 2013-08-14 | 2013-12-25 | 湖南三清药业有限公司 | Aspoxicillin compound, pharmaceutical composition, preparation and preparation method thereof |
-
2021
- 2021-11-18 CN CN202111366438.8A patent/CN114028345B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998022114A1 (en) * | 1996-11-15 | 1998-05-28 | Dumex-Alpharma A/S | A method for promoting tissue repair |
| WO2004066910A2 (en) * | 2003-01-31 | 2004-08-12 | Glenmark Pharmaceuticals Ltd. | Controlled release modifying complex and pharmaceutical compositions thereof |
| CN101862299A (en) * | 2009-04-17 | 2010-10-20 | 北京本草天源药物研究院 | Preparation method of aspoxicillin freeze-dried powder injection |
| CN103467492A (en) * | 2013-08-14 | 2013-12-25 | 湖南三清药业有限公司 | Aspoxicillin compound, pharmaceutical composition, preparation and preparation method thereof |
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