CN117982425B - Gentamicin sulfate soluble powder and preparation method and application thereof - Google Patents
Gentamicin sulfate soluble powder and preparation method and application thereof Download PDFInfo
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- CN117982425B CN117982425B CN202410094298.0A CN202410094298A CN117982425B CN 117982425 B CN117982425 B CN 117982425B CN 202410094298 A CN202410094298 A CN 202410094298A CN 117982425 B CN117982425 B CN 117982425B
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- soluble powder
- gentamicin sulfate
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- vaccine
- sulfate soluble
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- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.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.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](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 title claims abstract description 101
- 239000000843 powder Substances 0.000 title claims abstract description 95
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 229960005486 vaccine Drugs 0.000 claims abstract description 76
- -1 sucrose monohydrate ester Chemical class 0.000 claims abstract description 39
- 229930006000 Sucrose Natural products 0.000 claims abstract description 26
- 239000005720 sucrose Substances 0.000 claims abstract description 26
- 239000002904 solvent Substances 0.000 claims abstract description 25
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims abstract description 17
- 239000006184 cosolvent Substances 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 25
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 25
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 25
- 239000004359 castor oil Substances 0.000 claims description 20
- 235000019438 castor oil Nutrition 0.000 claims description 20
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 20
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 15
- 229930182566 Gentamicin Natural products 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 8
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 7
- 229920001983 poloxamer Polymers 0.000 claims description 7
- 229960000502 poloxamer Drugs 0.000 claims description 7
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 6
- 239000000194 fatty acid Substances 0.000 claims description 6
- 229930195729 fatty acid Natural products 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 6
- 238000001291 vacuum drying Methods 0.000 claims description 6
- 235000010234 sodium benzoate Nutrition 0.000 claims description 5
- 239000004299 sodium benzoate Substances 0.000 claims description 5
- RDEIXVOBVLKYNT-HDZPSJEVSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-[(1r)-1-aminoethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2 Chemical compound OS(O)(=O)=O.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.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](O2)[C@@H](C)N)N)[C@@H](N)C[C@H]1N.O1[C@H]([C@@H](C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-HDZPSJEVSA-N 0.000 claims description 4
- 238000004945 emulsification Methods 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- 229940124350 antibacterial drug Drugs 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 3
- 229960004025 sodium salicylate Drugs 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 7
- 230000003204 osmotic effect Effects 0.000 description 23
- 241000287828 Gallus gallus Species 0.000 description 13
- 230000000052 comparative effect Effects 0.000 description 13
- 235000013330 chicken meat Nutrition 0.000 description 12
- 238000012360 testing method Methods 0.000 description 11
- 229940031551 inactivated vaccine Drugs 0.000 description 10
- 239000003085 diluting agent Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 208000006758 Marek Disease Diseases 0.000 description 8
- 239000003921 oil Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 208000010359 Newcastle Disease Diseases 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 210000003746 feather Anatomy 0.000 description 5
- 229960002518 gentamicin Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000003739 neck Anatomy 0.000 description 4
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 244000144977 poultry Species 0.000 description 3
- 235000013594 poultry meat Nutrition 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000000811 xylitol Substances 0.000 description 3
- 229960002675 xylitol Drugs 0.000 description 3
- 235000010447 xylitol Nutrition 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- BKVAAWMQOQLENB-UHFFFAOYSA-N 15-hydroxy stearic acid Chemical group CCCC(O)CCCCCCCCCCCCCC(O)=O BKVAAWMQOQLENB-UHFFFAOYSA-N 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 241000701047 Gallid alphaherpesvirus 2 Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940126574 aminoglycoside antibiotic Drugs 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000832 effect on mycoplasma Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000001589 lymphoproliferative effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 229940044476 poloxamer 407 Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000009374 poultry farming Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000003612 virological effect Effects 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- 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
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16311—Mardivirus, e.g. Gallid herpesvirus 2, Marek-like viruses, turkey HV
- C12N2710/16334—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Medicinal Preparation (AREA)
Abstract
The application relates to the technical field of medicines, and in particular discloses gentamicin sulfate soluble powder as well as a preparation method and application thereof. The gentamicin sulfate soluble powder provided by the application comprises the following components in parts by weight: 30-50 parts of gentamicin sulfate, 10-30 parts of hydroxypropyl beta cyclodextrin and 15-35 parts of sucrose monohydrate ester; further, the gentamicin sulfate soluble powder also comprises 10-20 parts of cosolvent and 10-20 parts of solubilizer; the application also provides a preparation method of the gentamicin sulfate soluble powder and a pharmaceutical composition containing the gentamicin sulfate soluble powder. The gentamicin sulfate soluble powder provided by the application can be used in combination with various oily vaccines, and the titer of the Marek vaccine is not affected when the gentamicin sulfate soluble powder is used in combination with the Marek vaccine.
Description
Technical Field
The application relates to the technical field of medicines, in particular to gentamicin sulfate soluble powder and a preparation method and application thereof.
Background
In the poultry farming industry, farmers can vaccinate poultry and simultaneously add antibiotics and other antibacterial drugs into the vaccine, so that on one hand, the secondary infection of bacterial diseases caused by the reduction of the body resistance of the poultry caused by vaccination can be prevented, and on the other hand, the injection times can be reduced, and the stress response of the poultry can be reduced. Marek's Disease (MD) is a highly infectious, highly pathogenic, lymphoproliferative viral oncological disease caused by chicken infected with the pathogenic Marek's disease virus. At present, marek's disease is mainly prevented by Marek's vaccine, but Marek's vaccine is sensitive to the influence of pH value and osmotic pressure, and when the Marek's vaccine is combined with other medicines (most of the drugs are slightly acidic and few of the drugs are alkaline), the potency is easily influenced, so that the Marek's disease is immune failure, and the Marek's vaccine can only be combined with cephalosporin antibiotics at present.
Gentamicin sulfate is an aminoglycoside antibiotic, has strong inhibition and killing effects on various gram-negative bacteria and positive bacteria, and also has a certain effect on mycoplasma. The gentamicin sulfate is taken orally with little absorption, the intramuscular injection is absorbed rapidly and completely, and the bioavailability can reach 90 percent. However, the soluble powder of gentamicin sulfate is only soluble in water and insoluble in oil, so that the soluble powder cannot be combined with an oily vaccine, which greatly limits the application of the soluble powder.
Disclosure of Invention
In order to improve the oil solubility of gentamicin sulfate and simultaneously realize the combination of gentamicin sulfate and Marek's vaccine, the application provides gentamicin sulfate soluble powder and a preparation method and application thereof.
In a first aspect, the application provides gentamicin sulfate soluble powder, which adopts the following technical scheme:
the gentamicin sulfate soluble powder comprises the following components in parts by weight: 30-50 parts of gentamicin sulfate, 10-30 parts of hydroxypropyl beta cyclodextrin and 15-35 parts of sucrose monohydrate.
According to the application, the hydroxypropyl beta cyclodextrin and the sucrose monohydrate are added into the gentamicin sulfate, so that the prepared gentamicin sulfate soluble powder can be dissolved in water and oil, and the gentamicin sulfate soluble powder can be used in combination with an oily vaccine; in addition, when the gentamicin sulfate soluble powder is used in combination with a Marek vaccine, the potency of the Marek vaccine is not affected.
In the application, the hydroxypropyl beta cyclodextrin has good solubility in water, small viscosity and good fluidity, and can be mixed with gentamycin sulfate to improve the water solubility of the gentamycin sulfate on one hand and to improve the stability and bioavailability of the gentamycin sulfate on the other hand. The sucrose monohydrate ester contains a crystal water and contains ester groups on a molecular chain, so that the sucrose monohydrate ester has both hydrophilicity and lipophilicity, and the sucrose monohydrate ester is added into gentamicin sulfate, and the gentamicin sulfate soluble powder obtained through emulsification has excellent oil solubility and water solubility.
In some embodiments, the hydroxypropyl beta cyclodextrin may be 10-20 parts, 10-25 parts, 20-30 parts, or 25-30 parts by weight.
In a specific embodiment, the hydroxypropyl beta cyclodextrin may also be 10 parts, 20 parts, 25 parts, or 30 parts by weight.
In some embodiments, the sucrose monohydrate ester may be 15-20 parts, 15-25 parts, 15-30 parts, 20-25 parts, 20-30 parts, 20-35 parts, 25-30 parts, 25-35 parts, or 30-35 parts by weight.
In a specific embodiment, the sucrose monohydrate ester may also be 15 parts, 20 parts, 25 parts, 30 parts, or 35 parts by weight.
Optionally, the gentamicin sulfate soluble powder comprises the following components in parts by weight: 30-50 parts of gentamicin sulfate, 20-30 parts of hydroxypropyl beta cyclodextrin and 20-30 parts of sucrose monohydrate ester.
Optionally, the gentamicin sulfate soluble powder further comprises 10-20 parts of cosolvent and 10-20 parts of solubilizer.
Optionally, the cosolvent is selected from one or more of sucrose, sodium benzoate, and sodium salicylate; the solubilizer is one or more selected from Tween 20, tween 40, polyoxyethylene castor oil, poloxamer and sorbitan fatty acid ester.
In a specific embodiment, the solubilizing agent may be tween 20, polyoxyethylated castor oil or poloxamer, and may also be a mixture of tween 20 and polyoxyethylated castor oil, a mixture of tween 20 and poloxamer, or a mixture of tween 20 and sorbitan fatty acid ester.
Optionally, the solubilizing agent is a mixture of tween 20 and polyoxyethylated castor oil.
In some embodiments, the weight ratio of tween 20 and polyoxyethylated castor oil may be 2: (0.5-0.8), 2: (0.5-1.2), 2: (0.5-1.7), 2: (0.8-1.2), 2: (0.8-1.7), 2: (0.8-2.0), 2: (1.2-1.7), 2: (1.2-2.0) or 2: (1.7-2.0).
In a specific embodiment, the weight ratio of tween 20 and polyoxyethylated castor oil may also be 2:0.5, 2:0.8, 2:1.2, 2:1.7 or 2:2.0.
Optionally, the weight ratio of tween 20 to polyoxyethylated castor oil is 2: (0.8-1.7).
In a second aspect, the application provides a method for preparing gentamicin sulfate soluble powder, comprising the following steps: dissolving gentamicin sulfate in water, adding other components, stirring uniformly, adding a pH regulator after complete emulsification, regulating the pH value to 6.9-7.0, and carrying out vacuum drying and crushing to obtain gentamicin sulfate soluble powder with the particle size of 400-500 meshes.
Optionally, the vacuum drying process parameters are as follows: the temperature is 50-70deg.C, and the time is 3-5h.
In a third aspect, the application provides a pharmaceutical composition comprising the gentamicin sulfate soluble powder.
Optionally, the pharmaceutical composition further comprises an antibacterial drug or vaccine; the vaccine is Marek's vaccine or oily vaccine.
In the application, the gentamicin sulfate soluble powder has good oil solubility on one hand, can be mutually dissolved with oily vaccines (ND and H9) and does not have layering; on the other hand, when the gentamicin sulfate soluble powder is used in combination with the Marek vaccine, the potency of the Marek vaccine is not affected.
In summary, the application has the following beneficial effects:
1. The gentamicin sulfate soluble powder which can be dissolved in water and oil is prepared by using the gentamicin sulfate, the hydroxypropyl beta cyclodextrin and the sucrose monohydrate, so that the gentamicin sulfate soluble powder can be used in combination with a water-based vaccine or an oil-based vaccine; in addition, when the gentamicin hydrochloride soluble powder is used in combination with a Marek vaccine, the pH of the Marek vaccine is basically unchanged, and the potency of the Marek vaccine is basically unaffected.
2. The application further selects the following components in weight ratio: and (0.8-1.7) Tween 20 and polyoxyethylene castor oil are used as solubilizers, and when the obtained gentamicin sulfate soluble powder is used in combination with a Marek vaccine, the osmotic pressure change of the Marek vaccine is smaller, and the influence of the vaccine titer is smaller.
Detailed Description
The application provides gentamicin sulfate soluble powder which comprises the following components in parts by weight: 30-50 parts of gentamycin sulfate, 10-30 parts of hydroxypropyl beta cyclodextrin, 15-35 parts of sucrose monohydrate, 10-20 parts of cosolvent and 10-20 parts of solubilizer. Further, the gentamicin sulfate soluble powder comprises the following components in parts by weight: 30-50 parts of gentamycin sulfate, 20-30 parts of hydroxypropyl beta cyclodextrin, 20-30 parts of sucrose monohydrate ester, 10-20 parts of cosolvent and 10-20 parts of solubilizer.
Wherein the cosolvent is selected from one or more of sucrose, sodium benzoate and sodium salicylate; the solubilizer is one or more selected from Tween 20, tween 40, polyoxyethylene castor oil, poloxamer and sorbitan fatty acid ester. Further, the solubilizer is a mixture of tween 20 and polyoxyethylated castor oil. Still further, the weight ratio of tween 20 to polyoxyethylated castor oil is 2: (0.8-1.7).
The preparation method of the gentamicin sulfate soluble powder provided by the application comprises the following steps: dissolving gentamicin sulfate in water, adding other components, stirring uniformly, adding a pH regulator after complete emulsification, regulating the pH value to 6.9-7.0, vacuum drying at 50-70 ℃ for 3-5h, and crushing to obtain gentamicin sulfate soluble powder with the particle size of 400-500 meshes.
In the application, gentamicin sulfate is purchased from the Biotechnology Co., ltd. Of Heilongjiang Games Lin Hesai, and the CAS number of the hydroxypropyl beta cyclodextrin is 12846-35-5; sucrose monohydrate ester available from Jiangsu Jiujia biotechnology Co., ltd and having a CAS number of 37318-31-3; the CAS number of the sodium benzoate is 532-32-1; tween 20 was purchased from Alatin Biochemical technologies Co., ltd; polyoxyethylated castor oil EL35, available from biotechnology limited of shanxi Emperor Yao; the poloxamer is poloxamer 407, and is purchased from the company of the pharmaceutical excipients of the Siemens; sorbitan fatty acid esters are available from Wang Biotech Inc. of river Nankang. The remaining materials, reagents, solvents, etc. of the application are also commercially available.
The present application will be described in further detail with reference to examples and performance test.
Examples 1 to 8
Examples 1-8 provide a gentamicin sulfate soluble powder, respectively.
The above-described embodiments differ in that: the addition amounts of a part of the components in the gentamicin sulfate soluble powder are shown in the following table 1.
The preparation method of the gentamicin sulfate soluble powder provided in examples 1-8 comprises the following steps: dissolving 40g of gentamicin sulfate in 20g of water, adding 15g of hydroxypropyl beta cyclodextrin, sucrose monohydrate, cosolvent (sodium benzoate) and 15g of solubilizer (Tween 20), fully and uniformly stirring, completely emulsifying, adding a pH value regulator (phosphoric acid buffer solution), regulating the pH value to 7.0, vacuum drying at 60 ℃ for 4h, and carrying out superfine grinding by a jet mill to obtain gentamicin sulfate soluble powder with the particle size of 400-500 meshes.
TABLE 1 addition amount of partial components in gentamicin sulfate soluble powder provided in examples 1 to 8
Examples 9 to 17
Examples 9-17 provide a gentamicin sulfate soluble powder, respectively.
The above embodiment differs from embodiment 3 in that: the components and proportions of the solubilizer are shown in Table 2 below.
Table 2 examples 9-17 provide solubilizing agents in gentamicin sulfate soluble powders
Comparative example 1
Comparative example 1 provides a gentamicin sulfate soluble powder.
The above comparative example is different from example 3 in that: the adding amount of sucrose monohydrate ester in the gentamycin sulfate soluble powder is 0.
Comparative example 2
Comparative example 2 provides a gentamicin sulfate soluble powder.
The above comparative example is different from example 3 in that: the sucrose monohydrate ester in the gentamicin sulfate soluble powder was replaced with xylitol anhydride monostearate (available from Chongqing day run biologicals Co.).
Comparative example 3
Comparative example 3 provides a gentamicin sulfate soluble powder.
The above comparative example is different from example 3 in that: the sucrose monohydrate ester in the gentamicin sulfate soluble powder was replaced with 15-hydroxystearic acid polyethylene glycol ester (HS 15, available from Seaman pharmaceutical excipients Co., ltd.).
The performance detection test (I) combines gentamicin sulfate soluble powder with Marek vaccine, and explores the influence of the gentamicin sulfate soluble powder on the use performance of Marek vaccine.
1. Effect of gentamicin sulfate soluble powder on Marek vaccine pH
25ML of Marek's vaccine diluent (special diluent for chicken Marek's disease frozen vaccine, provided by Beijing feather company, package: 400 mL/bottle) is used for dissolving 5g of gentamicin sulfate soluble powder, shaking for 2-3min for complete dissolution, obtaining a sample to be tested, detecting the pH value of the sample to be tested, carrying out parallel test for 5 times, and taking an average value; the results of the test using chicken Marek's disease frozen vaccine as a blank are shown in Table 3.
Note that: when the pH value of the sample to be detected is between 6.9 and 7.1, the specification is met, and the titer of the Marek vaccine is not affected.
2. Influence of gentamicin sulfate soluble powder on osmotic pressure of Marek vaccine
Dissolving 5g gentamicin sulfate soluble powder by 25mL of Marek vaccine diluent, and shaking for 2-3min to completely dissolve to obtain a sample to be tested; detecting osmotic pressure of a sample to be detected by adopting a CM320 freezing point osmotic pressure tester, carrying out parallel test for 5 times, and taking an average value; the results of the frozen vaccine against chicken Marek's disease as a blank are shown in Table 3.
Note that: when the osmotic pressure of the sample to be tested is between 250 and 450mOsm/L, the sample meets the rule, and the titer of the Marek vaccine is not affected.
3. Vaccine cell viability assay
(1) Preparing a solution:
Preparation of test solution: measuring 50mL of Marek's special diluent in a 250mL triangular flask, adding 5g of accurately weighed test drug (gentamicin sulfate soluble powder provided by the application), adding a proper amount of Marek's frozen live vaccine (chicken Marek's disease frozen vaccine, CVI 988Rupens strain, package: 2000 parts per bottle), finally enabling the cell concentration to be 10 5-106/mL, shaking uniformly, and performing the measurement for 0h and 1 h.
Preparation of a control solution: and (3) measuring 50mL of Marek's special diluent in a 250mL triangular flask, adding a proper amount of Marek's frozen live vaccine, and finally enabling the cell concentration to be 10 5-106/mL, shaking uniformly, and performing measurement by acting for 0h and 1 h.
(2) And (3) measuring: taking 6mL of a sample solution to be tested, putting the sample solution into a centrifuge tube, centrifuging for 20min at 2000r/min, discarding supernatant, adding 3mL of Marek' S special diluent, shaking uniformly, taking 10 mu L of the solution, adding 10 mu L of 0.4% trypan blue staining solution, mixing uniformly, sucking 10 mu L of the mixed solution, adding the mixed solution into a disposable counting plate, standing horizontally for 30S, inserting the mixed solution into a cell counter for focusing, performing cell counting and activity calculation, recording the reading and storing. The control solution was assayed by the same method.
(3) The results were calculated as follows, and the test solution was measured 6 times to calculate the results as an average value. The degradation results are shown in table 3 below.
TABLE 3 Performance test results in examples 1-17 and comparative examples 1-3
According to the detection results of Table 3, after the gentamicin sulfate soluble powder obtained in examples 1-17 is mixed with Marek's vaccine, the pH value is between 6.9 and 7.1, the osmotic pressure range is between about 284 and 367mOsm/L, and the cell activity ratio is more than or equal to 0.95; the osmotic pressure of the gentamicin sulfate soluble powder prepared in comparative example 1 without adding sucrose monohydrate is up to 437mOsm/L, and the cell viability ratio of 1h is only 0.89 after the gentamicin sulfate soluble powder is mixed with Marek's vaccine; comparative example 2 gentamicin sulphate soluble powder prepared by xylitol anhydride monostearate is mixed with Marek's vaccine, the osmotic pressure is up to 415mOsm/L1h, and the cell activity ratio is 0.92; comparative example 3 gentamicin sulphate soluble powder prepared by xylitol anhydride monostearate is mixed with Marek's vaccine, the osmotic pressure is up to 430mOsm/L, and the 1h cell viability ratio is 0.94; the pH of the blank was 7.0 and the osmotic pressure range was approximately 268mOsm/L. Therefore, the gentamicin sulfate soluble powder provided by the application has little influence on the pH and osmotic pressure of the Marek vaccine, the pH value and the osmotic pressure are in a reasonable range and are closer to a blank group, and the gentamicin sulfate soluble powder provided by the application has no influence on the potency of the Marek vaccine.
The test results of examples 1-7 show that, as the addition amount of hydroxypropyl beta cyclodextrin and sucrose monohydrate ester increases, the pH value of the prepared gentamicin sulfate soluble powder is basically kept unchanged after being mixed with Marek vaccine, and the osmotic pressure is in a trend of decreasing first and then increasing second; in particular, the gentamicin sulfate soluble powder obtained in examples 2 to 4 and examples 6 to 7 was mixed with Marek's vaccine, and the osmotic pressure was less than 350mOsm/L. Therefore, the application shows that the application can obtain gentamicin sulfate soluble powder with smaller influence on the osmotic pressure of the Marek vaccine by controlling the adding amount of hydroxypropyl beta cyclodextrin between 20 and 30 parts and the adding amount of sucrose monohydrate ester between 20 and 30 parts, and the use of the gentamicin sulfate soluble powder and the Marek vaccine can not influence the potency of the gentamicin sulfate soluble powder.
As can be seen from the detection results of examples 3 and examples 9 to 17, the gentamicin sulfate soluble powder obtained by using only one solvent in examples 3 and examples 9 to 10 was mixed with Marek's vaccine, the pH value was 7.05, and the osmotic pressure was 321 to 356mOsm/L; example 16 uses a weight ratio of 2:1.2, wherein the mixture of Tween 20 and poloxamer is used as a solubilizer, and the obtained gentamicin sulfate soluble powder is mixed with Marek vaccine, and has a pH value of 7.04 and an osmotic pressure of 320mOsm/L; example 17 uses a weight ratio of 2:1.2, wherein the mixture of Tween 20 and sorbitan fatty acid ester is used as a solubilizer, and the obtained gentamicin sulfate soluble powder is mixed with a Marek vaccine, and has a pH value of 7.05 and an osmotic pressure of 316mOsm/L; whereas examples 11-15 used a weight ratio of 2: (0.5-2.0) tween 20 and polyoxyethylated castor oil as solubilizer, and the obtained gentamicin sulfate soluble powder is mixed with Marek vaccine, and the osmotic pressure is 284-314mOsm/L. The application is proved to adopt the mixture of Tween 20 and polyoxyethylene castor oil as the solubilizer, the obtained gentamicin sulfate soluble powder has smaller influence on the osmotic pressure of the Marek vaccine, and the combined use of the gentamicin sulfate soluble powder and the Marek vaccine does not influence the potency of the vaccine.
Further comparison shows that examples 12-14 control the weight ratio of tween 20 and polyoxyethylated castor oil to 2: (0.8-1.7), the obtained gentamicin sulfate soluble powder is mixed with Marek vaccine, and the osmotic pressure is less than 300mOsm/L and is more similar to that of a blank group. Therefore, the application is further illustrated to employ a weight ratio of 2: tween 20 and polyoxyethylene castor oil (0.8-1.7) are used as solubilizers, so that gentamycin sulfate soluble powder with smaller influence on the vaccine titer of the Marek vaccine can be obtained.
In summary, the application controls the weight parts of each component in the gentamicin sulfate soluble powder within the following range: 30-50 parts of gentamycin sulfate, 10-30 parts of hydroxypropyl beta cyclodextrin, 15-35 parts of sucrose monohydrate ester, 10-20 parts of cosolvent and 10-20 parts of solubilizer; the gentamicin sulfate soluble powder which is used together with the Marek vaccine and does not influence the potency of the Marek vaccine can be obtained; further, the weight ratio of the application is 2: the mixture of Tween 20 and polyoxyethylene castor oil (0.8-1.7) is used as a solubilizer, and the obtained gentamicin sulfate soluble powder has smaller osmotic pressure influence on the Marek vaccine.
(II) solubility test
(1) Firstly, 20g of gentamicin sulfate soluble powder is placed in 25mL of nano dispersion liquid provided by Rui first agriculture and sea company, and is vibrated for 2-3min to be completely dissolved, so as to obtain diluent; standing the diluted solution for 4 hours without layering and precipitation;
(2) And (2) adding 22mL of the diluent obtained in the step (1) into 500mL of ND Newcastle disease inactivated vaccine, repeatedly reversing to fully dissolve the diluent, standing for 192h, and observing whether layering and precipitation occur. The results are shown in Table 4 below.
TABLE 4 solubility test results
According to the test results of the solubility test in Table 4, the gentamicin sulfate soluble powder provided by the application can be dissolved in an oily vaccine (ND Newcastle disease inactivated vaccine), and does not have layering or precipitation after standing for 192 hours.
And thirdly, combining the gentamicin sulfate soluble powder with an oily vaccine, and exploring the influence of the gentamicin sulfate soluble powder on the potency of the oily vaccine.
1. Preparing injection:
(1) First, 20g of the gentamicin sulfate soluble powder of example 13 was dissolved in 1 bottle (25 mL) of a nano-dispersion (supplied by Rui first agriculture, shake and sea Co., ltd.) and shaken well for 3 minutes, and after complete dissolution, a diluted drug solution was obtained.
(2) And (3) extracting 11mL of the diluted liquid medicine by using a syringe, and injecting the diluted liquid medicine into 250mL of ND Newcastle disease inactivated vaccine to obtain gentamicin sulfate-ND combined injection.
11ML of the diluted liquid medicine is extracted by a syringe and injected into 250mL of H9 inactivated vaccine, and gentamicin sulfate-H9 combined injection is obtained.
2. Broiler test
(1) 400 Feather chickens are selected in a standardized white feather chicken cage farm and are divided into 4 groups of 100 chickens. Wherein, 1 group of feather chicken necks are subcutaneously injected with gentamicin sulfate-ND combined injection; the 1 group of feather chicken necks are subcutaneously injected with gentamicin sulfate-H9 combined injection; subcutaneously injecting an ND Newcastle disease inactivated vaccine into the chicken neck of the 1 group; subcutaneously injecting an H9 inactivated vaccine into the chicken neck of the 1 group; then, the breeding under the same conditions was performed under the same environment.
(2) Blood was collected at 1d, 7d, 14d, 21d, 28d, 35d, 42d days after injection, respectively, and standard antigens were assayed for ND antibody, H9 antibody, and HI antibody for H9,
3. The detection results are shown in Table 5 below.
TABLE 5 results of detection of oily vaccine titers
As can be seen from the detection results in Table 5, the potency of the ND Newcastle disease inactivated vaccine and the H9 inactivated vaccine is basically unaffected after the gentamycin sulfate soluble powder provided by the application is added into the ND Newcastle disease inactivated vaccine and the H9 inactivated vaccine. Therefore, the gentamicin sulfate soluble powder provided by the application can be used for combined injection with various oily vaccines, and the potency of the oily vaccines cannot be influenced. Furthermore, the combination reduces the number of injections to the birds, thereby reducing stress.
While the invention has been described in detail in the foregoing general description and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that modifications and improvements can be made thereto. Accordingly, such modifications or improvements may be made without departing from the spirit of the invention and are intended to be within the scope of the invention as claimed.
Claims (9)
1. The gentamicin sulfate soluble powder is characterized by comprising the following components in parts by weight: 30-50 parts of gentamycin sulfate, 10-30 parts of hydroxypropyl beta cyclodextrin, 15-35 parts of sucrose monohydrate, 10-20 parts of cosolvent and 10-20 parts of solubilizer.
2. The gentamicin sulfate soluble powder according to claim 1, wherein the gentamicin sulfate soluble powder comprises the following components in parts by weight: 30-50 parts of gentamicin sulfate, 20-30 parts of hydroxypropyl beta cyclodextrin and 20-30 parts of sucrose monohydrate ester.
3. The gentamicin sulphate soluble powder according to claim 1 wherein the co-solvent is selected from one or more of sucrose, sodium benzoate and sodium salicylate; the solubilizer is one or more selected from Tween 20, tween 40, polyoxyethylene castor oil, poloxamer and sorbitan fatty acid ester.
4. The gentamicin sulphate soluble powder according to claim 1 wherein the solubiliser is a mixture of tween 20 and polyoxyethylated castor oil.
5. The gentamicin sulfate soluble powder of claim 4 wherein the weight ratio of tween 20 to polyoxyethylated castor oil is 2: (0.8-1.7).
6. A method for preparing the gentamicin sulfate soluble powder as defined in any one of claims 1 to 5, comprising the steps of:
Dissolving gentamicin sulfate in water, adding other components, stirring uniformly, adding a pH regulator after complete emulsification, regulating the pH value to 6.9-7.0, and carrying out vacuum drying and crushing to obtain gentamicin sulfate soluble powder with the particle size of 400-500 meshes.
7. The method for preparing gentamicin sulfate soluble powder according to claim 6, wherein the process parameters of the vacuum drying are as follows: the temperature is 50-70deg.C, and the time is 3-5h.
8. A pharmaceutical composition comprising the gentamicin sulfate soluble powder of any one of claims 1 to 5.
9. The pharmaceutical composition of claim 8, wherein the pharmaceutical composition further comprises an antibacterial drug or a vaccine; the vaccine is Marek's vaccine or oily vaccine.
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