CN114146058A - Etimicin sulfate freeze-dried powder injection and preparation method thereof - Google Patents
Etimicin sulfate freeze-dried powder injection and preparation method thereof Download PDFInfo
- Publication number
- CN114146058A CN114146058A CN202010930941.0A CN202010930941A CN114146058A CN 114146058 A CN114146058 A CN 114146058A CN 202010930941 A CN202010930941 A CN 202010930941A CN 114146058 A CN114146058 A CN 114146058A
- Authority
- CN
- China
- Prior art keywords
- freeze
- drying
- etimicin sulfate
- dried powder
- maintaining
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229950009953 etimicin Drugs 0.000 title claims abstract description 55
- OEBISAUVQBGQKC-ZIZSAZPJSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4-amino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]oxy-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;sulfuric acid Chemical compound OS(O)(=O)=O.O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](NC)[C@@](C)(O)CO1)O)NCC)[C@H]1O[C@H](CN)CC[C@H]1N OEBISAUVQBGQKC-ZIZSAZPJSA-N 0.000 title claims abstract description 50
- 238000002347 injection Methods 0.000 title claims abstract description 46
- 239000007924 injection Substances 0.000 title claims abstract description 46
- 239000000843 powder Substances 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000004108 freeze drying Methods 0.000 claims abstract description 39
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 13
- 239000011780 sodium chloride Substances 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims description 36
- 238000010438 heat treatment Methods 0.000 claims description 22
- 238000000859 sublimation Methods 0.000 claims description 20
- 230000008022 sublimation Effects 0.000 claims description 20
- 238000007710 freezing Methods 0.000 claims description 15
- 230000008014 freezing Effects 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 229920002307 Dextran Polymers 0.000 claims description 9
- 239000003963 antioxidant agent Substances 0.000 claims description 7
- 230000003078 antioxidant effect Effects 0.000 claims description 7
- 239000008176 lyophilized powder Substances 0.000 claims description 7
- 229930182555 Penicillin Natural products 0.000 claims description 6
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 6
- 229940049954 penicillin Drugs 0.000 claims description 6
- VEGXETMJINRLTH-ALRICIOSSA-N etimicin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@H](O)[C@H]1O[C@@H]1[C@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N VEGXETMJINRLTH-ALRICIOSSA-N 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000008215 water for injection Substances 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 2
- 238000007599 discharging Methods 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 238000005265 energy consumption Methods 0.000 abstract description 2
- 229940101006 anhydrous sodium sulfite Drugs 0.000 description 8
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 5
- 238000001514 detection method Methods 0.000 description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 3
- 229940001584 sodium metabisulfite Drugs 0.000 description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960002668 sodium chloride Drugs 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 241000589220 Acetobacter Species 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010063057 Cystitis noninfective Diseases 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- 208000032376 Lung infection Diseases 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010037597 Pyelonephritis acute Diseases 0.000 description 1
- 206010037601 Pyelonephritis chronic Diseases 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000001555 acute pyelonephritis Diseases 0.000 description 1
- 229940126574 aminoglycoside antibiotic Drugs 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 201000003139 chronic cystitis Diseases 0.000 description 1
- 201000006368 chronic pyelonephritis Diseases 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K47/02—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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61P31/04—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)
- Inorganic Chemistry (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an etimicin sulfate freeze-dried powder injection and a preparation method thereof. The freeze-dried powder injection does not contain sodium chloride, has high clarity after redissolution, and improves the safety of clinical use of the product. The freeze-drying process optimizes the freeze-drying curve of more than 70h in the prior art to about 24h, thereby obviously reducing the production energy consumption and the cost; the freeze-dried powder injection obtained by the freeze-drying process has low water content and high product quality.
Description
Technical Field
The invention relates to an etimicin sulfate preparation, in particular to an etimicin sulfate freeze-dried powder injection and a preparation method thereof.
Background
Etimicin sulfate is a new-generation semi-synthetic aminoglycoside antibiotic with high efficiency, low toxicity and drug-resistant bacteria and independent intellectual property rights. Etimicin sulfate is suitable for various infections caused by Escherichia coli, Klebsiella pneumoniae, Serratia, Acetobacter trifoliatus, Enterobacter, Acinetobacter, Proteus, Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus, etc., to which it is sensitive. Clinical research shows that the product has better curative effect on the following infections: such as acute bronchitis, acute attack of chronic bronchitis, community lung infection, etc. Kidney and urogenital infections: such as acute pyelonephritis, cystitis, chronic pyelonephritis or chronic cystitis. Cutaneous soft tissue and other infections: such as skin and soft tissue infections, infections after trauma, trauma and surgery and other sensitive bacterial infections.
The etimicin sulfate preparation can be injection, lyophilized powder for injection, etc. The existing prescription of the freeze-dried powder injection comprises etimicin sulfate, sodium metabisulfite, low molecular dextran and sodium chloride. When the freeze-dried powder injection is prepared, low-molecular dextran is dissolved in boiling water, sodium metabisulfite, sodium chloride and etimicin sulfate intermediate liquid medicine are added after the mixture is cooled, the mixture is canned into penicillin bottles, each bottle is filled with 2mL, and the freeze-dried powder injection is obtained after freeze-drying. The lyophilization profile is as follows: pre-freezing: reaching-45 ℃ within 1h and maintaining for 1 h; sublimation drying: heating to-15 ℃ within 3h, and maintaining for 55 h; and (3) resolving and drying: heating to 5 ℃ within 1 hour and maintaining for 4-6 hours. The sublimation drying time of the existing freeze-drying process is as long as 70 hours; in addition the freeze-dried product had a slightly higher moisture content.
Disclosure of Invention
The invention aims to solve the technical problem of providing an etimicin sulfate freeze-dried powder injection with high clarity after redissolution and a preparation method of the freeze-dried powder injection with short production time and low water content of products.
The technical scheme for realizing the first purpose of the invention is that the etimicin sulfate freeze-dried powder injection comprises etimicin sulfate and an antioxidant; sodium chloride is not included.
The etimicin sulfate freeze-dried powder injection is prepared by freeze-drying a liquid medicine containing 50-100 mg/mL (calculated by etimicin) of etimicin sulfate and 0.1-0.2 wt% of antioxidant.
The etimicin sulfate freeze-dried powder injection also comprises low molecular dextran, and the content of the low molecular dextran in the liquid medicine prepared before freeze-drying is 0.5 wt% -1 wt%.
The technical scheme for realizing the second purpose of the invention is the preparation method of the etimicin sulfate freeze-dried powder injection, which comprises the following steps: dissolving the active ingredients and the auxiliary materials in water for injection, uniformly mixing, and fixing the volume to obtain a liquid medicine; filtering, subpackaging into penicillin bottles, freeze-drying according to the following freeze-drying curve, and discharging from a box:
pre-freezing: reaching-45 ℃ within 1-1.5 h and maintaining for 1-2.5 h.
② sublimation drying: heating to-10 to-15 ℃ within 2-3 h, and maintaining for 10-12 h; heating to-5-0 ℃ within 1-2 h, and maintaining for 2-4 h.
Analysis and drying: heating to 25-30 ℃ within 1h, and maintaining for 3-6 h.
Alternatively, the lyophilization profile is as follows:
pre-freezing: reaching-45 ℃ within 1.5h and maintaining for 2.5 h;
② sublimation drying: heating to-15 ℃ within 2h, and maintaining for 12 h; heating to-5 ℃ within 2h, and maintaining for 3 h;
analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
The invention has the positive effects that:
(1) the freeze-dried powder injection does not contain sodium chloride, has high clarity after redissolution, and improves the safety of clinical use of the product.
(2) The freeze-drying process optimizes the freeze-drying curve of more than 70h in the prior art to about 24h, thereby obviously reducing the production energy consumption and the cost; the freeze-dried powder injection obtained by the freeze-drying process has low water content and high product quality.
Detailed Description
(example 1)
The etimicin sulfate freeze-dried powder injection comprises etimicin sulfate and antioxidant anhydrous sodium sulfite. The antioxidant may also be sodium metabisulfite.
The etimicin sulfate freeze-dried powder injection of the embodiment is obtained by freeze-drying a liquid medicine containing 50mg/mL (calculated by etimicin) of etimicin sulfate and 0.2 wt% of antioxidant.
The preparation method comprises the following steps: dissolving 9.96g of etimicin sulfate and 0.51g of anhydrous sodium sulfite in 200mL of water for injection, uniformly mixing and fixing the volume; after filtering, subpackaging 2mL of liquid medicine into a penicillin bottle, and taking out of the box after freeze-drying according to the following freeze-drying curve:
pre-freezing: reach-45 ℃ within 1.5h and maintain for 2.5 h.
② sublimation drying: heating to-15 ℃ within 2h, and maintaining for 12 h; then the temperature is raised to-5 ℃ within 2h and maintained for 3 h.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
(example 2)
The etimicin sulfate freeze-dried powder injection comprises etimicin sulfate, anhydrous sodium sulfite and sodium chloride.
The etimicin sulfate freeze-dried powder injection of the embodiment is obtained by freeze-drying a liquid medicine containing 50mg/mL (calculated as etimicin) of etimicin sulfate, 0.2 wt% of anhydrous sodium sulfite and 0.9 wt% of sodium chloride.
The preparation method comprises the following steps: dissolving 9.96g of etimicin sulfate, 0.51g of anhydrous sodium sulfite and 2.3g of sodium chloride in 200mL of water for injection, uniformly mixing and fixing the volume; and (3) after filtering, subpackaging 2mL of liquid medicine into a penicillin bottle, and obtaining the freeze-dried powder injection according to the method of the embodiment 1.
(example 3)
The etimicin sulfate freeze-dried powder injection comprises etimicin sulfate, anhydrous sodium sulfite and low-molecular dextran.
The etimicin sulfate freeze-dried powder injection of the embodiment is obtained by freeze-drying a liquid medicine containing 50mg/mL (calculated by etimicin) of etimicin sulfate, 0.2 wt% of anhydrous sodium sulfite and 1 wt% of low molecular dextran.
The preparation method comprises the following steps: dissolving 9.96g of etimicin sulfate, 0.51g of anhydrous sodium sulfite and 2.6g of low-molecular dextran in 200mL of water for injection, uniformly mixing and fixing the volume; and (3) after filtering, subpackaging 2mL of liquid medicine into a penicillin bottle, and obtaining the freeze-dried powder injection according to the method of the embodiment 1.
The appearance and index of the freeze-dried powder injection obtained in the examples 1 to 3 are as follows:
compared with the prior art, the sublimation drying time of the embodiment 1 is shortened by nearly 30h, the desorption drying temperature is increased to be close to room temperature, the moisture of the obtained product is basically not higher than 4%, the production cost is reduced, and the product quality is also improved.
The clarity and the redissolution time of the examples 1 and 3 are obviously better than those of the example 2, which shows that the clarity of the product without sodium chloride in the formula is obviously better than that of the product with sodium chloride.
(example 4)
The formula of the etimicin sulfate freeze-dried powder injection in the embodiment is the same as that in the embodiment 1, and the freeze-drying curve is as follows:
pre-freezing: reach-45 ℃ in 1h and maintain for 2.5 h.
② sublimation drying: heating to-10 ℃ within 2h, and maintaining for 10 h; then, the temperature was raised to 0 ℃ over 2 hours and maintained for 3 hours.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
(example 5)
The formula of the etimicin sulfate freeze-dried powder injection in the embodiment is the same as that in the embodiment 1, and the freeze-drying curve is as follows:
pre-freezing: reach-45 ℃ within 1.5h and maintain for 2.5 h.
② sublimation drying: heating to-5 ℃ within 3h, and maintaining for 10 h; then the temperature was raised to 0 ℃ over 2 h.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
(example 6)
The formula of the etimicin sulfate freeze-dried powder injection in the embodiment is the same as that in the embodiment 1, and the freeze-drying curve is as follows:
pre-freezing: reach-45 ℃ within 1.5h and maintain for 2.5 h.
② sublimation drying: heating to-5 ℃ within 3 h; then, the temperature was raised to 0 ℃ over 1 hour and maintained for 11 hours.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
The appearance and index of the freeze-dried powder injection obtained in the examples 1, 4, 5 and 6 are as follows:
sublimation drying is the most important in the freeze-drying process, and the freeze-dried powder injections of examples 1, 4, 5 and 6 have no significant difference among detection indexes. Therefore, compared with the existing freeze-drying process, the prescription and the freeze-drying process adopted in the invention can obviously reduce the production cost on the premise of ensuring the product quality.
(example 7)
The formula of the etimicin sulfate freeze-dried powder injection in the embodiment is the same as that in the embodiment 3, and the freeze-drying curve is as follows:
pre-freezing: reach-45 ℃ within 1.5h and maintain for 2.5 h.
② sublimation drying: heating to-10 ℃ within 2h, and maintaining for 10 h; then, the temperature was raised to 0 ℃ over 2 hours and maintained for 3 hours.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
(example 8)
The formula of the etimicin sulfate freeze-dried powder injection in the embodiment is the same as that in the embodiment 3, and the freeze-drying curve is as follows:
pre-freezing: reach-45 ℃ within 1.5h and maintain for 2.5 h.
② sublimation drying: heating to-5 ℃ within 3h, and maintaining for 10 h; then the temperature was raised to 0 ℃ over 2 h.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
(example 9)
The formula of the etimicin sulfate freeze-dried powder injection in the embodiment is the same as that in the embodiment 3, and the freeze-drying curve is as follows:
pre-freezing: reach-45 ℃ within 1.5h and maintain for 2.5 h.
② sublimation drying: heating to-5 ℃ within 3 h; then, the temperature was raised to 0 ℃ over 1 hour and maintained for 11 hours.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
The appearance and index of the lyophilized powder obtained in examples 3, 7, 8 and 9 were as follows:
compared with different freeze-drying processes, the clarity of the freeze-drying liquid is obviously improved along with the reduction of the sublimation drying temperature, and other detection indexes have no significant difference.
(example 10)
The formula of the etimicin sulfate freeze-dried powder injection in the embodiment is the same as that in the embodiment 2, and the freeze-drying curve is as follows:
pre-freezing: reach-45 ℃ within 1.5h and maintain for 2.5 h.
② sublimation drying: heating to-10 ℃ within 2h, and maintaining for 10 h; then, the temperature was raised to 0 ℃ over 2 hours and maintained for 3 hours.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
(example 11)
The formula of the etimicin sulfate freeze-dried powder injection in the embodiment is the same as that in the embodiment 2, and the freeze-drying curve is as follows:
pre-freezing: reach-45 ℃ within 1.5h and maintain for 2.5 h.
② sublimation drying: heating to-5 ℃ within 3h, and maintaining for 10 h; then the temperature was raised to 0 ℃ over 2 h.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
(example 12)
The formula of the etimicin sulfate freeze-dried powder injection in the embodiment is the same as that in the embodiment 2, and the freeze-drying curve is as follows:
pre-freezing: reach-45 ℃ within 1.5h and maintain for 2.5 h.
② sublimation drying: heating to-5 ℃ within 3 h; then, the temperature was raised to 0 ℃ over 1 hour and maintained for 11 hours.
Analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
The appearance and index of the lyophilized powder obtained in examples 2, 10, 11 and 12 are as follows:
compared with different freeze-drying processes, the clarity of the freeze-drying liquid is obviously improved along with the reduction of the sublimation drying temperature, and other detection indexes have no significant difference.
Claims (6)
1. An etimicin sulfate freeze-dried powder injection is characterized in that: comprises etimicin sulfate and an antioxidant.
2. The etimicin sulfate lyophilized powder for injection as claimed in claim 1, wherein: sodium chloride is not included.
3. The etimicin sulfate lyophilized powder for injection as claimed in claim 1, wherein: the etimicin sulfate freeze-dried powder injection is prepared by freeze-drying a liquid medicine containing 50-100 mg/mL (calculated by etimicin) of etimicin sulfate and 0.1-0.2 wt% of antioxidant.
4. The etimicin sulfate lyophilized powder for injection as claimed in claim 3, wherein: also comprises low molecular dextran, wherein the content of the low molecular dextran in the liquid medicine is 0.5 wt% -1 wt%.
5. The preparation method of the etimicin sulfate freeze-dried powder injection as claimed in claim 1, which is characterized by comprising the following steps: dissolving the active ingredients and the auxiliary materials in water for injection, uniformly mixing, and fixing the volume to obtain a liquid medicine; filtering, subpackaging into penicillin bottles, freeze-drying according to the following freeze-drying curve, and discharging from a box:
pre-freezing: reaching-45 ℃ within 1-1.5 h, and maintaining for 1-2.5 h;
② sublimation drying: heating to-10 to-15 ℃ within 2-3 h, and maintaining for 10-12 h; heating to-5-0 ℃ within 1-2 h, and maintaining for 2-4 h;
analysis and drying: heating to 25-30 ℃ within 1h, and maintaining for 3-6 h.
6. The method for preparing etimicin sulfate lyophilized powder for injection according to claim 5, wherein the lyophilization curve is as follows:
pre-freezing: reaching-45 ℃ within 1.5h and maintaining for 2.5 h;
② sublimation drying: heating to-15 ℃ within 2h, and maintaining for 12 h; heating to-5 ℃ within 2h, and maintaining for 3 h;
analysis and drying: the temperature is raised to 25 ℃ within 1h and maintained for 3 h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010930941.0A CN114146058A (en) | 2020-09-07 | 2020-09-07 | Etimicin sulfate freeze-dried powder injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010930941.0A CN114146058A (en) | 2020-09-07 | 2020-09-07 | Etimicin sulfate freeze-dried powder injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114146058A true CN114146058A (en) | 2022-03-08 |
Family
ID=80461084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010930941.0A Pending CN114146058A (en) | 2020-09-07 | 2020-09-07 | Etimicin sulfate freeze-dried powder injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114146058A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1569010A (en) * | 2004-04-29 | 2005-01-26 | 浙江大学 | Etimicin sulfate preparation and its preparing method |
| US20090156517A1 (en) * | 2006-08-25 | 2009-06-18 | Hesheng Zhang | Stable pharmaceutical compositions of aminoglycoside antibiotics, ion-chelating agents, and buffers |
| CN102525963A (en) * | 2012-02-08 | 2012-07-04 | 武汉普生制药有限公司 | Netilmicin sulfate lyophiled powder injection and preparation method thereof |
| CN105012250A (en) * | 2015-08-03 | 2015-11-04 | 湖南科伦制药有限公司 | Method for preparing netilmicin sulfate freeze-dried powder injection |
-
2020
- 2020-09-07 CN CN202010930941.0A patent/CN114146058A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1569010A (en) * | 2004-04-29 | 2005-01-26 | 浙江大学 | Etimicin sulfate preparation and its preparing method |
| US20090156517A1 (en) * | 2006-08-25 | 2009-06-18 | Hesheng Zhang | Stable pharmaceutical compositions of aminoglycoside antibiotics, ion-chelating agents, and buffers |
| CN102525963A (en) * | 2012-02-08 | 2012-07-04 | 武汉普生制药有限公司 | Netilmicin sulfate lyophiled powder injection and preparation method thereof |
| CN105012250A (en) * | 2015-08-03 | 2015-11-04 | 湖南科伦制药有限公司 | Method for preparing netilmicin sulfate freeze-dried powder injection |
Non-Patent Citations (3)
| Title |
|---|
| 吴新红等: ""头孢匹胺钠与硫酸依替米星存在配伍禁忌"", 《护理实践与研究》 * |
| 国家药典委员会编: "《中华人民共和国药典：2010年版：第一增补本》", 31 August 2012, 中国医药科技出版社 * |
| 国家药典委员会编: "《中华人民共和国药典：二部注释（2015年版）》", 31 October 2019, 中国医药科技出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2062582B1 (en) | Antibiotic composition comprising beta-lactam antibiotics, aminoglycosides and buffers | |
| Naylor et al. | Factors affecting the viability of Serratia marcescens during dehydration and storage | |
| CN101559040A (en) | Medicament composition of cefotiam hydrochloride and preparation thereof | |
| US20190133953A1 (en) | Preparation Method of Azacitidine for Injection | |
| CN102731585B (en) | New active clindamycin phosphate compound and medicinal composition thereof | |
| CN114788814B (en) | High-stability daptomycin composition for injection and preparation method and application thereof | |
| CN114146058A (en) | Etimicin sulfate freeze-dried powder injection and preparation method thereof | |
| CN106798731B (en) | Preparation method of florfenicol soluble powder | |
| US4261977A (en) | Streptomycetal antibiotic | |
| CN102106857A (en) | Compound ceftiofur sodium freeze-dried power injection used for injection | |
| CN103585018A (en) | New freeze-drying method for reduced glutathione for injection | |
| CN111346061A (en) | Chlorogenic acid composition and preparation method thereof | |
| US4162304A (en) | Streptomycetal antibiotic | |
| CN103191062A (en) | Sulbenicillin sodium injection | |
| CN114028345B (en) | Aspoxicillin freeze-dried agent for injection and preparation process thereof | |
| CN112137969A (en) | Enoxaparin sodium for injection containing enoxaparin sodium and preparation method thereof | |
| CN101849916B (en) | Cefpiramide sodium powder injection and preparation method thereof | |
| CN107652306B (en) | Cefuroxime sodium crystal compound | |
| CN115381825B (en) | Nicotil pharmaceutical composition and preparation method thereof | |
| CN105362236B (en) | A kind of mensiso freeze-dried powder and preparation method thereof | |
| CN117618342B (en) | Preparation method of amikacin sulfate injection | |
| CN103735522A (en) | Andrographolide freeze-dried powder and preparation method thereof | |
| AU2021106002A4 (en) | Extraction and preparation of the acidic polysaccharide extracted from Kaempfeia galangal L and its application in antibacterial preservation | |
| CN102824310A (en) | Cefotiam-hydrochloride-containing medicine preparation and preparation method thereof | |
| CN113876722B (en) | Aztreonam for injection and preparation method thereof |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20220308 |