CN116637075B - Amoxicillin powder with high water solubility and preparation method thereof - Google Patents
Amoxicillin powder with high water solubility and preparation method thereof Download PDFInfo
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- CN116637075B CN116637075B CN202310606200.0A CN202310606200A CN116637075B CN 116637075 B CN116637075 B CN 116637075B CN 202310606200 A CN202310606200 A CN 202310606200A CN 116637075 B CN116637075 B CN 116637075B
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- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 title claims abstract description 69
- 229960003022 amoxicillin Drugs 0.000 title claims abstract description 69
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 title claims abstract description 69
- 239000000843 powder Substances 0.000 title claims abstract description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 229920002472 Starch Polymers 0.000 claims abstract description 64
- 239000008107 starch Substances 0.000 claims abstract description 64
- 235000019698 starch Nutrition 0.000 claims abstract description 64
- 239000002994 raw material Substances 0.000 claims abstract description 23
- 238000002156 mixing Methods 0.000 claims abstract description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 15
- 238000004880 explosion Methods 0.000 claims abstract description 15
- 244000068988 Glycine max Species 0.000 claims abstract description 12
- 235000010469 Glycine max Nutrition 0.000 claims abstract description 12
- 150000004676 glycans Chemical class 0.000 claims abstract description 12
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 12
- 239000005017 polysaccharide Substances 0.000 claims abstract description 12
- 244000269722 Thea sinensis Species 0.000 claims abstract description 9
- 150000008442 polyphenolic compounds Chemical class 0.000 claims abstract description 9
- 235000013824 polyphenols Nutrition 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 16
- 239000002002 slurry Substances 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 239000012153 distilled water Substances 0.000 claims description 8
- 239000007789 gas Substances 0.000 claims description 7
- 238000000227 grinding Methods 0.000 claims description 7
- 238000009736 wetting Methods 0.000 claims description 7
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 229920000945 Amylopectin Polymers 0.000 claims description 3
- 229920000856 Amylose Polymers 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 238000010979 pH adjustment Methods 0.000 claims description 2
- 238000007873 sieving Methods 0.000 claims description 2
- 238000003860 storage Methods 0.000 abstract description 15
- 230000006866 deterioration Effects 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 5
- 230000007547 defect Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000009700 powder processing Methods 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 description 6
- 239000011521 glass Substances 0.000 description 5
- 206010035664 Pneumonia Diseases 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000006184 cosolvent Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 229960001031 glucose Drugs 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 206010034107 Pasteurella infections Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 201000005115 pasteurellosis Diseases 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 201000006509 pleuropneumonia Diseases 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000004383 yellowing 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
- A61K9/141—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
- A61K9/146—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 macromolecular 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- 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
- A61K9/143—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 inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—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
- A61K9/148—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 compounds of unknown constitution, e.g. material from plants or animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention provides amoxicillin powder with high water solubility and a preparation method thereof, and relates to the technical field of amoxicillin powder processing. The high water-solubility amoxicillin powder is mainly prepared by mixing amoxicillin, modified water-solubility starch, water-solubility soybean polysaccharide, anhydrous sodium carbonate, tea polyphenol and the like, and the modified water-solubility starch is mainly prepared by subjecting starch raw materials to air explosion and alkaline gelatinization. The invention overcomes the defects of the prior art, can effectively ensure the water solubility of the amoxicillin powder, further improve the long-acting storage stability of the amoxicillin powder, reduce the storage loss of the amoxicillin powder, improve the use safety of medicines and prevent deterioration.
Description
Technical Field
The invention relates to the technical field of amoxicillin powder processing, in particular to amoxicillin powder with high water solubility and a preparation method thereof.
Background
Amoxicillin, also known as amoxicillin, belongs to a semisynthetic broad-spectrum antibiotic, and acts as an antibacterial agent by inhibiting the synthesis of bacterial cell walls. Is suitable for respiratory system infection, urinary tract infection and some infections caused by gram-negative bacillus, such as calf pneumonia, colt pneumonia, bovine pasteurellosis, mastitis, pneumonia, swine infectious pleuropneumonia, pullorum disease, colibacillosis, fowl typhoid, etc.
In order to improve the solubility of amoxicillin powder, cosolvent such as sodium carbonate is generally added in the powder preparation process to increase the water solubility of amoxicillin, but the addition of the substances can cause easy yellowing and deterioration of amoxicillin powder during storage, which affects the use quality of the whole product to a certain extent;
the patent number CN202111089691.3 discloses a preparation method of amoxicillin soluble powder, wherein an alkaline cosolvent and amoxicillin raw materials are physically isolated by adopting a principle of glucose fusion coating in the powder, so that the solubility of the amoxicillin soluble powder is ensured, and meanwhile, the deterioration of the amoxicillin soluble powder in the storage process is effectively prevented, but the anhydrous glucose fused powder added in the patent is isolated, but the anhydrous glucose fused powder has certain hygroscopicity, and the physical isolation effect is finally reduced due to the fact that the water vapor in the absorption environment is absorbed in the long-term storage process, so that the deterioration caused by the contact of the alkaline cosolvent and the amoxicillin raw materials is also caused to a certain extent, and the preparation of the amoxicillin medicament for reducing the consumption of the amoxicillin medicament in the veterinary medicament, which can ensure the water solubility and effectively prevent the storage deterioration thereof, is a large research direction in the prior art.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the amoxicillin powder with high water solubility and the preparation method thereof, which can effectively ensure the water solubility of the amoxicillin powder, further improve the long-acting storage stability of the amoxicillin powder, reduce the storage loss of the amoxicillin powder, improve the use safety of medicines and prevent deterioration.
In order to achieve the above object, the technical scheme of the present invention is realized by the following technical scheme:
the high water-solubility amoxicillin powder is prepared from the following raw materials in parts by weight: 25-32 parts of amoxicillin, 14-18 parts of modified water-soluble starch, 6-8 parts of water-soluble soybean polysaccharide, 3-5 parts of anhydrous sodium carbonate, 1-3 parts of tea polyphenol and 0.8-1.2 parts of solubilizer.
Preferably, the modified water-soluble starch is prepared by carrying out gas explosion treatment on a starch raw material, then carrying out gelatinization treatment under alkaline conditions, and then regulating to be neutral and drying.
Preferably, the specific preparation method of the modified water-soluble starch comprises the following steps:
(1) and (3) carrying out gas explosion treatment on the starch raw material: adding distilled water into the starch raw material, mixing, preheating for 10-20min at 60 ℃, then placing in a high-pressure reaction kettle, heating to 180-200 ℃, adjusting the pressure to 2-4Mpa, and carrying out gas explosion treatment for 40-60s to obtain pretreated starch slurry for later use;
(2) alkali treatment: regulating pH of the pretreated starch slurry to 8-9, stirring and mixing at 70 ℃ in water bath for 1-2h for gelatinization, regulating to neutrality, and drying at 40-60 ℃ at constant temperature to obtain modified water-soluble starch.
Preferably, in the step (2), sodium hydroxide and dilute sulfuric acid solution are used for pH adjustment.
Preferably, the ratio of amylopectin to amylose in the starch material is 3-4:1-1.5.
Preferably, the solubilizer is any one of sodium dodecyl sulfate or sodium dodecyl sulfate.
The preparation method of the amoxicillin powder with high water solubility comprises the following steps:
(1) Raw material oxidation pretreatment: mixing the modified water-soluble starch and the water-soluble soybean polysaccharide, dissolving in distilled water, then introducing oxygen into the mixture, and stirring the mixture for 1 to 2 hours to obtain pre-oxidized slurry;
(2) And (3) slurry drying treatment: adding anhydrous sodium carbonate into the pre-oxidized slurry, fully and uniformly stirring, freeze-drying, adding tea polyphenol and amoxicillin, mixing and grinding to obtain a mixture for later use;
(3) And (3) mixing: and adding the mixture into a solubilizer, wetting by steam, fully stirring, drying, and grinding into powder to obtain amoxicillin powder with high water solubility.
Preferably, the whole stirring process of introducing oxygen in the step (1) is carried out under the water bath environment with the temperature of 65 ℃.
Preferably, the mixture in the step (2) is ground and sieved by a 80-mesh sieve.
Preferably, the temperature of the steam wetting in the step (3) is 45-60 ℃, and the total moisture content of the wetting is 20-40%.
The invention provides amoxicillin powder with high water solubility and a preparation method thereof, which has the advantages compared with the prior art that:
(1) According to the invention, the amoxicillin powder is prepared by mixing amoxicillin with raw materials such as modified water-soluble starch, water-soluble soybean polysaccharide, tea polyphenol and the like, so that the water solubility of the amoxicillin powder can be effectively ensured, meanwhile, the modified water-soluble starch is subjected to air explosion treatment, then is gelatinized by alkali liquor, the overall water solubility of the starch is improved, meanwhile, the excessive moisture absorption of the starch raw materials in the air is effectively prevented, the powder deterioration caused by excessive moisture absorption of the starch raw materials in the air is effectively prevented, the modified water-soluble starch can absorb certain moisture in the moist air, and then forms a certain film layer outside according to the viscosity of the modified water-soluble starch to cover the amoxicillin to a certain extent, the moisture in the air is prevented from further contacting with the powder in the air, and meanwhile, the film layer can be rapidly disintegrated in the water, and the solubility of the amoxicillin is not influenced.
(2) According to the preparation method, the modified water-soluble starch and the water-soluble soybean polysaccharide are pre-oxidized in the preparation process, so that the water solubility of the modified water-soluble starch and the water-soluble soybean polysaccharide can be further improved, the performance change caused by oxidation in the subsequent normal-temperature storage process is prevented, and the anhydrous sodium carbonate is added for mixing, so that the oxidized modified water-soluble starch and the oxidized water-soluble soybean polysaccharide wrap the sodium carbonate component, the sodium carbonate component is prevented from being directly contacted with the amoxicillin component, and the outer wrapping layer is not easy to absorb moisture and disintegrate in the storage process, so that the storage stability of the modified water-soluble starch and the water-soluble soybean polysaccharide is ensured.
(3) The tea polyphenol is added in the invention, so that the integral oxidation resistance of the water-soluble amoxicillin powder can be effectively improved, the oxidation and deterioration of the powder in the long-term storage process can be prevented, the content of active ingredients of amoxicillin can be ensured, and the storage stability of the whole powder can be improved.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions in the embodiments of the present invention will be clearly and completely described in the following in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The following examples and comparative examples used the following raw materials:
amoxicillin: purity 99%, water solubility 4g/L at normal temperature, all together with a biotechnology (Shanghai) limited company;
starch: corn starch (about 75% amylopectin and about 25% amylose);
water-soluble soybean polysaccharide: shanghai Spectrum family Biotechnology Co., ltd;
anhydrous sodium carbonate: analytically pure (Shanghai ether chemical technology Co., ltd.);
tea polyphenols, sodium dodecyl sulfonate: tianjin Seen Biochemical technologies Co., ltd;
anhydrous sodium carbonate: tianjin gold sink Taiya chemical Co.
Example 1:
treatment of starch raw materials:
1. preparation of modified water-soluble starch:
(1) adding distilled water into the starch raw material, mixing, preheating for 10-20min at 60 ℃, then placing the mixture into a high-pressure reaction kettle, heating to 200 ℃, adjusting the pressure to 2Mpa, and carrying out gas explosion treatment for 50s to obtain pretreated starch slurry for later use;
(2) adding sodium hydroxide into the pretreated starch slurry to adjust the pH to 8.5, stirring and mixing for 1.5h at the water bath temperature of 70 ℃ for gelatinization treatment, adding dilute sulfuric acid solution to adjust to neutrality, and drying at the constant temperature of 50 ℃ to obtain modified water-soluble starch;
2. preparation of water-soluble starch:
(1) adding distilled water into the starch raw material, uniformly mixing and stirring, adding sodium hydroxide to adjust the pH value to 8.5, stirring and mixing for 1.5 hours at the water bath temperature of 70 ℃ for gelatinization treatment, adding dilute sulfuric acid solution to adjust to neutrality, and drying at the constant temperature of 50 ℃ to obtain water-soluble starch;
3. preparation of air explosion starch:
(1) adding distilled water into the starch raw material, mixing, preheating for 10-20min at 60 ℃, then placing in a high-pressure reaction kettle, heating to 200 ℃, adjusting the pressure to 2Mpa, performing air explosion treatment for 50s to obtain starch slurry, and drying at the constant temperature of 50 ℃ to obtain air explosion starch;
the water solubility of the modified water-soluble starch, the water-soluble starch and the air explosion starch is detected respectively, wherein the specific detection mode is that each group of starch materials is added into clear water at the normal temperature of 20 ℃ (the starch materials are stirred for 1min at the stirring speed of 60r/min without precipitation to be completely dissolved), and the completely dissolved amount of each group of starch in 100ml of water solution is recorded, and the specific results are shown in the following table 1:
TABLE 1
| Group of | Modified water-soluble starch | Water-soluble starch | Air explosion starch |
| Dissolving quantity (g/ml) | 72 | 63 | 60 |
From table 1 above, it is clear that the modified water-soluble starch has good solubility.
Example 2:
preparation of amoxicillin powder with high water solubility:
(1) Mixing 16g of the modified water-soluble starch in the embodiment 1 and 7g of water-soluble soybean polysaccharide, dissolving in 100ml of distilled water, heating to 65 ℃ for water bath heat preservation, and introducing oxygen into the mixture to stir for 1.5 hours to obtain pre-oxidized slurry;
(2) Adding 4g of anhydrous sodium carbonate into the pre-oxidized slurry, fully and uniformly stirring, then lyophilizing, adding 2g of tea polyphenol and 30g of amoxicillin, mixing, grinding and sieving with a 80-mesh sieve to obtain a mixture for later use;
(3) Adding 1g of sodium dodecyl sulfate into the mixture, wetting the mixture to the water content of 25% by adopting hot steam at 50 ℃, fully stirring for 30min, drying at the constant temperature of 45 ℃, and grinding into powder to obtain the amoxicillin powder with high water solubility.
Example 3:
the raw material selections were made according to table 2 below, with the preparation of the water-soluble amoxicillin powder according to the preparation method described in example 2 above:
TABLE 2
The amounts of the other substances added in each experimental group in the above table were the same as in example 2.
And (3) detection:
performance tests were performed on the water-soluble amoxicillin powders produced in experimental groups 1-4 in example 2 and example 3 above (wherein the amoxicillin content in each group of powders was 50%):
1. and (3) water solubility detection:
dissolving each group of water-soluble amoxicillin powder in 100ml of water at 22+/-2 ℃, adding each group of powder according to the time, weighing 0.1g each time, adding the powder into the water, stirring for 3min, continuing adding until no precipitate exists after stirring, recording the total amount of the precipitate, and after adding the maximum dissolving amount of each group of powder, uniformly stirring, standing for 30min, observing whether the solution is uniform and clear, wherein the specific results are shown in the following table 3:
TABLE 3 Table 3
From the above table 3, it can be seen that the modified water-soluble starch obtained after the air explosion and alkaline gelatinization of the starch can effectively improve the solubility of the whole powder and further improve the uniformity of the solution after the fractional dissolution.
2. The storage stability of each group of powders was tested:
detecting the water content and amoxicillin content change of the powder before and after the test (wherein the amoxicillin content is detected by adopting an HPLC method)
(1) Short-term stability detection:
subpackaging each group of powder samples into glass bottles, and carrying out strong light irradiation test by adopting the illumination intensity of 4000 lx; placing the sample in a 60 ℃ incubator for high-temperature test; placing in an environment with the relative humidity of 90% +/-2% at 23+/-2 ℃ for high-humidity test; the change in the 8d and 15d properties of the powders under each test condition was recorded, and the specific results are shown in table 4 below:
table 4:
as can be seen from table 4, the water-soluble amoxicillin powder prepared in example 2 has higher stability under short-term strong light, high temperature and high humidity conditions;
(2) Long-term stability test: each group of powder samples was packaged in glass bottles (4 glass bottles were set in each group), and the powder samples were stored under a light-shielding and sealing condition for 12 months at a temperature of 22±3 ℃ and a relative humidity of 80%, and were sampled at the end of the 3 rd, 6 th, 9 th and 12 th months (one glass bottle was taken separately during sampling, and the samples in the glass bottles were mixed and stirred uniformly before sampling), and the changes in the water content and amoxicillin content (the water content and amoxicillin content before each group of tests were shown in table 4, as shown in table 5 below) were measured:
TABLE 5
From the above table, the addition of the modified water-soluble starch in example 2 can effectively improve the stability of the final amoxicillin powder and prevent storage deterioration.
It is noted that relational terms such as first and second, and the like are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising one … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises the element.
The above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (7)
1. The amoxicillin powder with high water solubility is characterized by being prepared from the following raw materials in parts by weight: 25-32 parts of amoxicillin, 14-18 parts of modified water-soluble starch, 6-8 parts of water-soluble soybean polysaccharide, 3-5 parts of anhydrous sodium carbonate, 1-3 parts of tea polyphenol and 0.8-1.2 parts of solubilizer;
the modified water-soluble starch is prepared by carrying out gas explosion treatment on a starch raw material, then carrying out gelatinization treatment under an alkaline condition, and then regulating to be neutral and drying, and the specific preparation method comprises the following steps:
(1) and (3) carrying out gas explosion treatment on the starch raw material: adding distilled water into the starch raw material, mixing, preheating for 10-20min at 60 ℃, then placing in a high-pressure reaction kettle, heating to 180-200 ℃, adjusting the pressure to 2-4Mpa, and carrying out gas explosion treatment for 40-60s to obtain pretreated starch slurry for later use;
(2) alkali treatment: regulating the pH of the pretreated starch slurry to 8-9, stirring and mixing at 70 ℃ in a water bath for 1-2h for gelatinization treatment, regulating to neutrality, and drying at 40-60 ℃ at constant temperature to obtain modified water-soluble starch;
the preparation method of the amoxicillin powder with high water solubility comprises the following steps:
(1) Raw material oxidation pretreatment: mixing the modified water-soluble starch and the water-soluble soybean polysaccharide, dissolving in distilled water, then introducing oxygen into the mixture, and stirring the mixture for 1 to 2 hours to obtain pre-oxidized slurry;
(2) And (3) slurry drying treatment: adding anhydrous sodium carbonate into the pre-oxidized slurry, fully and uniformly stirring, freeze-drying, adding tea polyphenol and amoxicillin, mixing and grinding to obtain a mixture for later use;
(3) And (3) mixing: and adding the mixture into a solubilizer, wetting by steam, fully stirring, drying, and grinding into powder to obtain amoxicillin powder with high water solubility.
2. The amoxicillin powder with high water solubility according to claim 1, wherein the modified water-soluble starch is prepared in step (2) by pH adjustment using sodium hydroxide and dilute sulfuric acid solution.
3. A highly water soluble amoxicillin powder according to any one of claims 1 to 2, characterised in that: the ratio of the amylopectin to the amylose in the starch raw material is 3-4:1-1.5.
4. A highly water-soluble amoxicillin powder as claimed in claim 1, characterized in that: the solubilizer is any one of sodium dodecyl sulfate or sodium dodecyl sulfate.
5. A highly water-soluble amoxicillin powder as claimed in claim 1, characterized in that: the whole process of introducing oxygen and stirring in the step (1) of preparing the amoxicillin powder with high water solubility is carried out under the water bath environment with the temperature of 65 ℃.
6. A highly water-soluble amoxicillin powder as claimed in claim 1, characterized in that: and (3) grinding the mixture in the step (2) of preparing the amoxicillin powder with high water solubility, and sieving the mixture with a 80-mesh sieve.
7. A highly water-soluble amoxicillin powder as claimed in claim 1, characterized in that: the temperature of steam wetting in the step (3) of preparing the amoxicillin powder with high water solubility is 45-60 ℃, and the total moisture content of wetting is 20-40%.
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| WO2020087904A1 (en) * | 2018-11-01 | 2020-05-07 | 江南大学 | Ph-sensitive starch-based microcapsule and method for preparation thereof |
| CN111529493A (en) * | 2020-05-30 | 2020-08-14 | 潍坊中科力邦生物工程研究院 | Amoxicillin soluble powder easy to dissolve in water and high in stability and preparation method thereof |
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| JP5612152B1 (en) * | 2013-04-12 | 2014-10-22 | 三和澱粉工業株式会社 | Method for producing modified starch and modified starch |
| WO2020087904A1 (en) * | 2018-11-01 | 2020-05-07 | 江南大学 | Ph-sensitive starch-based microcapsule and method for preparation thereof |
| CN111529493A (en) * | 2020-05-30 | 2020-08-14 | 潍坊中科力邦生物工程研究院 | Amoxicillin soluble powder easy to dissolve in water and high in stability and preparation method thereof |
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