CN111110627B - Amikacin sulfate injection and preparation method thereof - Google Patents
Amikacin sulfate injection and preparation method thereof Download PDFInfo
- Publication number
- CN111110627B CN111110627B CN201811278757.1A CN201811278757A CN111110627B CN 111110627 B CN111110627 B CN 111110627B CN 201811278757 A CN201811278757 A CN 201811278757A CN 111110627 B CN111110627 B CN 111110627B
- Authority
- CN
- China
- Prior art keywords
- injection
- amikacin sulfate
- acetate
- sodium
- buffering agent
- 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.)
- Active
Links
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
-
- 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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an amikacin sulfate injection taking acetate as a buffering agent and a preparation method thereof, the injection contains active ingredient amikacin sulfate, the buffering agent, an antioxidant and a pH regulator, the buffering agent is acetate, and the pH value range of the injection is 3.5-5.5. The invention has the advantages that the thermal stability of the amikacin sulfate injection is improved, and the acetate is taken as a buffering agent, so that the degradation of the amikacin sulfate in the process of moist heat sterilization is effectively reduced, and the stability of the pharmaceutical preparation in the processes of transportation and storage is ensured.
Description
Technical Field
The invention relates to a stable amikacin sulfate injection and a preparation method thereof.
Background
Amikacin sulfate injection belongs to semi-synthetic aminoglycoside antibiotics, is stable to most aminoglycoside inactivating enzymes, is particularly suitable for treating serious infection caused by gram-negative bacilli to kanamycin, gentamicin or tobramycin resistant strains, and is widely applied clinically.
The existing amikacin sulfate injection prescription can be summarized into two types, one type does not contain a buffering agent, and the other type contains citrate as a buffering agent. The former does not contain a buffering agent, and the pH value of the product cannot be kept stable in the processes of transportation and storage; the latter contains citrate, the citrate reacts with amikacin sulfate under heating, after moist heat sterilization, a plurality of unknown impurities are generated, the regulation of ICH impurity quality control limit is exceeded, the impurities are in a growing trend in the storage process, no literature report about the safety of the impurities exists at present, the safety and the effectiveness of the product have great risks, and the prescription of the product needs to be improved.
Disclosure of Invention
In order to solve the problems, the invention provides a stable amikacin sulfate injection taking sodium acetate as a buffering agent.
The invention provides an amikacin sulfate injection which contains an active ingredient amikacin sulfate, a buffering agent, an antioxidant and a pH regulator, wherein the buffering agent is acetate, and the pH value of the injection is 3.5-5.5, preferably 4.5-5.0.
The invention has the advantages that the thermal stability of the amikacin sulfate injection is improved, and the acetate is taken as a buffering agent, so that the degradation of the amikacin sulfate in the process of moist heat sterilization is effectively reduced, and the stability of the pharmaceutical preparation in the processes of transportation and storage is ensured.
Preferably, the amikacin sulfate injection solution of the invention, wherein the buffer is selected from sodium acetate or potassium acetate; the buffer is preferably sodium acetate.
Preferably, the amikacin sulfate injection of the invention, wherein the antioxidant is selected from sodium metabisulfite, sodium sulfite, sodium bisulfite or sodium thiosulfate, preferably sodium metabisulfite.
Preferably, the amikacin sulfate injection of the invention, wherein the pH regulator is selected from sulfuric acid, hydrochloric acid or acetic acid; the pH regulator is preferably sulfuric acid.
Preferably, the amikacin sulfate injection of the invention, wherein the concentration of acetate in the injection is in the range of 0.01-20mg/ml; the preferred concentration is 9.7-18mg/ml; most preferably at a concentration of 15-17mg/ml.
According to the invention, the acetate buffer is added into the amikacin sulfate, and the type and concentration range of the buffer are controlled at the same time, so that the problem of impurity increase of the amikacin sulfate injection after moist heat sterilization and in the storage process is solved, the defects of the prior art are overcome, the impurities in the product are greatly reduced, the stability of the product is improved to a great extent, and the product is easy to store and transport; meanwhile, because the impurities are greatly reduced, the safety and the effectiveness of the product are also improved, and the safe and effective guarantee is provided for the clinical application of the product.
The invention also provides a method for preparing the amikacin sulfate injection, which comprises the following steps:
a) Adding a buffering agent, an antioxidant and amikacin sulfate into water for injection, and stirring for dissolving;
b) Adding a pH regulator into the solution obtained in the step a), and regulating the pH value to 3.5-5.5;
c) Filtering the solution obtained in the step b), and subpackaging;
d) Sterilizing by moist heat to obtain the injection product,
wherein, the antioxidant is sodium pyrosulfite or sodium sulfite, the pH regulator is sulfuric acid, the pH value adjusting range is preferably 4.5-5.0, the buffering agent is sodium acetate, and the concentration range of the sodium acetate is 0.01-20mg/ml, preferably 9.7-18mg/ml, and most preferably 15-17mg/ml.
The preparation method provided by the invention is simple to operate, easy for large-scale production, and the obtained product is low in impurity content and good in stability.
Detailed Description
The invention is further illustrated by the following specific examples. It should be understood that: the examples of the present invention are provided for illustration only and not for limitation of the present invention. The technical scheme obtained by simply improving the invention or equivalently replacing the conventional means or components on the basis of the technical scheme of the invention belongs to the protection scope of the invention.
In order to investigate the influence of sodium citrate on amikacin sulfate injection impurities, the inventors carried out the following experiment-
The first experimental example: amikacin sulfate impurity influence factor experiment
The experimental materials were: the samples prepared according to the prescription on the market, the blank auxiliary material without active ingredients, the sample containing sodium citrate and the sample without sodium citrate are detailed in the table 1-
TABLE 1 preparation of Experimental prescription samples of amikacin sulfate injection
Each of the above samples was prepared and put into an ampoule, and subjected to moist heat sterilization (121 ℃ C. For 15 min), and the results of comparing the impurity conditions before and after sterilization are shown in Table 2:
TABLE 2 comparison of impurity detection before and after sterilization
The results show that the impurities of the sodium citrate-containing sample are obviously higher than those of other formulas after sterilization, which indicates that amikacin sulfate and sodium citrate have certain effects under high temperature conditions to cause the generation of impurities.
The inventor finally obtains the stable amikacin sulfate injection preparation formula through a series of research experiments, screening and verification, and a group of examples comprise:
example 1
| Main medicine/auxiliary material | Final concentration |
| Amikacin sulfate | 250mg/ml |
| Sodium acetate | 16mg/ml |
| Sodium metabisulfite | 6.6mg/ml |
| Sulfuric acid | Adjusting pH to 4.5 |
| Water for injection | Adding to 1ml |
The preparation process comprises the following steps:
a) Adding sodium acetate, sodium metabisulfite and amikacin sulfate into 75 percent of the final volume of water for injection, and stirring for dissolving;
b) Adding dilute sulfuric acid into the solution obtained in the step a), and adjusting the pH value to 4.5;
c) Filtering the solution obtained in the step b) and subpackaging;
d) Sterilizing by moist heat to obtain the injection product.
Example 2
| Main medicine/auxiliary material | Final concentration |
| Amikacin sulfate | 250mg/ml |
| Sodium acetate | 9.7mg/ml |
| Sodium metabisulfite | 6.6mg/ml |
| Sulfuric acid | Adjusting pH to 4.5 |
| Water for injection | Adding to 1ml |
The preparation process comprises the following steps:
a) Adding sodium acetate, sodium metabisulfite and amikacin sulfate into 75 percent of the final volume of water for injection, and stirring for dissolving; b) Adding dilute sulfuric acid into the solution obtained in the step a), and adjusting the pH value to 4.5;
c) Filtering the solution obtained in the step b) and subpackaging;
d) And (5) sterilizing by moist heat to obtain the injection product.
Example 3
| Main medicine/auxiliary material | Final concentration |
| Amikacin sulfate | 250mg/ml |
| Sodium acetate | 18mg/ml |
| Sodium metabisulfite | 6.6mg/ml |
| Sulfuric acid | Adjusting pH to 4.5 |
| Water for injection | Adding to 1ml |
The preparation process comprises the following steps:
a) Adding sodium acetate, sodium metabisulfite and amikacin sulfate into 75 percent of the final volume of water for injection, and stirring for dissolving; b) Adding dilute sulfuric acid into the solution obtained in the step a), and adjusting the pH value to 4.5;
c) Filtering the solution obtained in the step b) and subpackaging;
d) Sterilizing by moist heat to obtain the injection product.
Example 4
| Main medicine/auxiliary material | Final concentration |
| Amikacin sulfate | 250mg/ml |
| Sodium acetate | 16mg/ml |
| Sodium sulfite | 4mg/ml |
| Sulfuric acid | Adjusting pH to 5.0 |
| Water for injection | Adding to 1ml |
The preparation process comprises the following steps:
a) Adding sodium acetate, sodium sulfite and amikacin sulfate into 75 percent of the final volume of water for injection, stirring and dissolving;
b) Adding dilute sulfuric acid into the solution obtained in the step a), and adjusting the pH value to 5.0;
c) Filtering the solution obtained in the step b) and subpackaging;
d) Sterilizing by moist heat to obtain the injection product.
Example 5
| Main medicine/auxiliary material | Final concentration |
| Amikacin sulfate | 250mg/ml |
| Sodium acetate | 16mg/ml |
| Sodium bisulfite | 6mg/ml |
| Sulfuric acid | Adjusting pH to 4.5 |
| Water for injection | Adding to 1ml |
The preparation process comprises the following steps:
a) Adding sodium acetate, sodium bisulfite and amikacin sulfate into 75% of the final volume of water for injection, and stirring for dissolving;
b) Adding dilute sulfuric acid into the solution obtained in the step a), and adjusting the pH value to 4.5;
c) Filtering the solution obtained in the step b) and subpackaging;
d) Sterilizing by moist heat to obtain the injection product.
Example 6
| Main medicine/auxiliary material | Final concentration |
| Amikacin sulfate | 100mg/ml |
| Sodium acetate | 16mg/ml |
| Sodium bisulfite | 6mg/ml |
| Sulfuric acid | Adjusting pH to 3.5 |
| Water for injection | Adding to 1ml |
The preparation process comprises the following steps:
a) Adding sodium acetate, sodium bisulfite and amikacin sulfate into 80% of the final volume of water for injection, and stirring for dissolving;
b) Adding dilute sulfuric acid into the solution obtained in the step a), and adjusting the pH value to 3.5;
c) Filtering the solution obtained in the step b) and subpackaging;
d) And (5) sterilizing by moist heat to obtain the injection product.
To further confirm the quality of the injection solution product (sodium acetate as a buffer), the inventors conducted comparative studies on examples 1, 2 and 4 of the present invention and the original formulation of amikacin sulfate injection (sodium citrate as a buffer), including the resistance to moist heat sterilization and the sensitivity of the injection to light and high temperature, as follows:
experimental example ii comparative experiment for resistance to moist heat sterilization:
the samples of example 1, example 2 and example 4 and the typical prescription sample of the amikacin sulfate injection on the market at present are subjected to moist heat sterilization (121 ℃ for 15 min), and the change of impurities before and after the moist heat sterilization of the samples is examined. The results show that: many impurity peaks are generated after the sodium citrate prescription is sterilized, impurities are not obviously changed before and after the sodium acetate prescription is sterilized, and total impurities of the sodium citrate prescription are obviously higher than those of the sodium acetate prescription. The sodium acetate is shown as a buffering agent to effectively improve the stability of the amikacin sulfate injection in the process of moist heat sterilization, and the detailed results are shown in the following table 3:
TABLE 3 examination results of impurities before and after sterilization of different buffer salt samples
Experimental example three influencing factors comparative experiment:
samples of example 1, example 2 and amikacin sulfate injection were each exposed to light (1.4X 10) and the formulation was originally marketed (sodium citrate as buffer) 6 Lux hr) and high temperature (60 ℃ C.) were left for 10 days to examine the stability of the sample. The results are shown in Table 4:
TABLE 4 different buffer salt samples influence factor test results
As can be seen from table 4: the impurities of the three samples have no obvious change after 10 days of illumination; the impurities in the sodium acetate formula (examples 1 and 2) are slightly increased after 10 days of high temperature, and the impurities in the sodium citrate formula are obviously increased after 10 days of high temperature. The results show that: compared with the sodium citrate prescription, the sodium acetate is used as a buffering agent to effectively reduce the degradation of the amikacin sulfate injection.
The test results prove that: the sodium acetate is used as a buffering agent, so that the degradation of amikacin sulfate in the process of moist heat sterilization can be reduced, the stability of a pharmaceutical preparation in the processes of transportation and storage is ensured, the purity of the pharmaceutical preparation is ensured, the generation of impurities is reduced, the toxic or side effect of the pharmaceutical preparation is reduced, the medication risk is reduced, and the safety of the pharmaceutical preparation is improved.
Claims (3)
1. An amikacin sulfate injection consists of active ingredients of amikacin sulfate, a buffering agent, an antioxidant, a pH regulator and water for injection, and is characterized in that: the buffer is acetate, the pH value of the injection is 4.5-5.0,
the buffer agent is sodium acetate, and the buffer agent is sodium acetate,
the antioxidant is sodium metabisulfite,
the pH regulator is sulfuric acid, and the pH regulator is a sodium hydroxide,
the concentration range of acetate in the injection is 9.7-18mg/ml,
the concentration of the active ingredient amikacin sulfate in the injection is 250mg/ml or 100mg/ml.
2. The injection of claim 1, wherein the concentration of acetate in the injection is in the range of 15-17mg/ml.
3. A method for preparing the amikacin sulfate injection of claim 1, comprising the steps of:
a) Adding a buffering agent, an antioxidant and amikacin sulfate into water for injection, and stirring for dissolving;
b) Adding a pH regulator into the solution obtained in the step a), and regulating the pH value to 4.5-5.0;
c) Filtering the solution obtained in the step b), and subpackaging;
d) Sterilizing by moist heat to obtain the injection product,
wherein the antioxidant is sodium metabisulfite, the pH regulator is sulfuric acid, the buffer is sodium acetate, and the concentration range of the sodium acetate is 9.7-18 mg/ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811278757.1A CN111110627B (en) | 2018-10-30 | 2018-10-30 | Amikacin sulfate injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811278757.1A CN111110627B (en) | 2018-10-30 | 2018-10-30 | Amikacin sulfate injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111110627A CN111110627A (en) | 2020-05-08 |
| CN111110627B true CN111110627B (en) | 2022-12-02 |
Family
ID=70484658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811278757.1A Active CN111110627B (en) | 2018-10-30 | 2018-10-30 | Amikacin sulfate injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111110627B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111904929B (en) * | 2020-06-28 | 2023-02-07 | 江苏吴中医药集团有限公司 | Amikacin sulfate injection and preparation method thereof |
| CN115282116B (en) * | 2022-08-19 | 2023-04-18 | 浙江和沐康医药科技有限公司 | Amikacin injection and preparation method thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101129383A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing aminoglycoside antibiotic |
| WO2008028347A1 (en) * | 2006-08-25 | 2008-03-13 | Tianjin Hemay Bio-Tech Co. Ltd | Combined antibiotics preparation |
| CN101239070A (en) * | 2008-03-13 | 2008-08-13 | 四川川投医药生物技术有限责任公司 | Eyedrops for curing eye affection and uses thereof |
| CN101584658A (en) * | 2009-07-03 | 2009-11-25 | 上海恒丰强动物药业有限公司 | Preparation method of amikacin sulfate injection |
| CN102755286A (en) * | 2012-07-04 | 2012-10-31 | 天津金耀集团有限公司 | Gentamycin sulfate injection containing buffer agent |
| CN103181890A (en) * | 2011-12-27 | 2013-07-03 | 四川科伦药物研究有限公司 | Amikacin sulphate injection and preparation method for same |
| CN104237228A (en) * | 2013-06-20 | 2014-12-24 | 上海信谊金朱药业有限公司 | Method for testing amikacin sulfate injection |
| CN107115281A (en) * | 2016-02-25 | 2017-09-01 | 上海信谊金朱药业有限公司 | The preparation method of amikacin sulfate injection |
-
2018
- 2018-10-30 CN CN201811278757.1A patent/CN111110627B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101129383A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing aminoglycoside antibiotic |
| WO2008028347A1 (en) * | 2006-08-25 | 2008-03-13 | Tianjin Hemay Bio-Tech Co. Ltd | Combined antibiotics preparation |
| CN101239070A (en) * | 2008-03-13 | 2008-08-13 | 四川川投医药生物技术有限责任公司 | Eyedrops for curing eye affection and uses thereof |
| CN101584658A (en) * | 2009-07-03 | 2009-11-25 | 上海恒丰强动物药业有限公司 | Preparation method of amikacin sulfate injection |
| CN103181890A (en) * | 2011-12-27 | 2013-07-03 | 四川科伦药物研究有限公司 | Amikacin sulphate injection and preparation method for same |
| CN102755286A (en) * | 2012-07-04 | 2012-10-31 | 天津金耀集团有限公司 | Gentamycin sulfate injection containing buffer agent |
| CN104237228A (en) * | 2013-06-20 | 2014-12-24 | 上海信谊金朱药业有限公司 | Method for testing amikacin sulfate injection |
| CN107115281A (en) * | 2016-02-25 | 2017-09-01 | 上海信谊金朱药业有限公司 | The preparation method of amikacin sulfate injection |
Non-Patent Citations (1)
| Title |
|---|
| 硫酸阿米卡星注射液生产工艺研究;来萍利等;《中国药业》;20131020;第22卷(第20期);58-59 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111110627A (en) | 2020-05-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111110627B (en) | Amikacin sulfate injection and preparation method thereof | |
| US3962430A (en) | Sterilization of solid non-electrolyte medicinal agents employing sodium chloride | |
| CN111569054A (en) | Gynecological antibacterial gel and preparation method thereof | |
| WO2023087578A1 (en) | Urapidil hydrochloride injection and preparation method therefor | |
| WO2021058014A1 (en) | Ornidazole pharmaceutical composition and preparation method and use thereof | |
| CN117205151A (en) | Amikacin sulfate injection and preparation method thereof | |
| CN102643255B (en) | Andrographolide compound | |
| WO2022227115A1 (en) | Preparation method for sisomicin sulfate sterile powder injection for injection | |
| CN114262477B (en) | Packaging container for inhibiting tobramycin eye drops from changing color and preparation method thereof | |
| CN113398066A (en) | Levofloxacin hydrochloride and sodium chloride injection for pets and preparation method thereof | |
| CN107970244B (en) | Composition containing ciprofloxacin and dexamethasone and preparation method thereof | |
| CN113730348B (en) | Dexamethasone sodium phosphate injection and preparation method thereof | |
| CN110946860A (en) | Composition containing omeprazole sodium and preparation method thereof | |
| CN113018443B (en) | Pharmaceutical composition for treating respiratory system diseases and preparation method thereof | |
| CN110882221B (en) | Production process of carfilzomib freeze-dried preparation for injection | |
| CN113069422B (en) | Preparation method of cefbuperazone sodium freeze-dried powder injection for injection | |
| CN103735522A (en) | Andrographolide freeze-dried powder and preparation method thereof | |
| CN113694032B (en) | Methylprednisolone sodium succinate freeze-dried powder injection for injection and preparation method thereof | |
| CN117298042A (en) | Amikacin sulfate injection and preparation method thereof | |
| CN113143866B (en) | Gentamicin sulfate particles capable of preventing degradation and deterioration of main medicine | |
| CN115364048A (en) | Preparation method of brivaracetam injection | |
| CN106822147B (en) | Composition of ceftriaxone sodium and sulbactam sodium, pharmaceutical preparation containing composition and application of pharmaceutical preparation | |
| CN114224830A (en) | Single-dose bacteriostatic-free ophthalmic preparation and preparation method thereof | |
| CN115671044A (en) | Netilmicin sulfate injection and preparation method thereof | |
| CN115105465A (en) | Adrenaline hydrochloride injection and its preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |