CN113304112B - Amoxicillin soluble powder and preparation method thereof - Google Patents
Amoxicillin soluble powder and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/146—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
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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
Abstract
The invention relates to amoxicillin soluble powder and a preparation method thereof. The amoxicillin soluble powder comprises: 27-33 parts of amoxicillin; 1.8-2.2 parts of cosolvent; the cosolvent is one or more of polyvinylpyrrolidone, polyethylene glycol 6000, polyethylene glycol 4000 and polyethylene glycol 2000; 0.45-0.55 part of stabilizer; the stabilizer is selected from one or a combination of more of disodium ethylene diamine tetraacetate, sodium hexametaphosphate and sodium tripolyphosphate; 59-74 parts of a diluent; the diluent is selected from one or a combination of more of anhydrous glucose, lactose and water-soluble starch. The amoxicillin soluble powder has higher solubility and better stability.
Description
Technical Field
The invention relates to amoxicillin soluble powder and a preparation method thereof.
Background
The amoxicillin belongs to beta-lactam antibiotics, is a semi-synthetic penicillin broad-spectrum antibiotic which is most widely applied, is white or white-like crystalline powder, is quickly absorbed by oral administration, and has strong antibacterial and bactericidal effects. The antibacterial activity against most gram-positive bacteria is slightly weaker than that of penicillin, and the antibacterial agent has stronger effects on gram-negative bacteria such as Escherichia coli, salmonella, haemophilus and Pasteurella, and is sensitive to penicillinase, so that the antibacterial agent is ineffective against penicillin-resistant Staphylococcus aureus. Is very suitable for treating gram-positive bacteria and gram-negative bacteria infection of the chicken sensitive to amoxicillin and systemic infection of respiratory system, urinary system, skin, soft tissue and the like caused by sensitive bacteria. As early as the sixties of the 20 th century, amoxicillin has been developed by Bichester, UK.
Amoxicillin has strong bactericidal effect and strong cell wall penetrating capacity. After oral administration, lactam group in drug molecules is immediately hydrolyzed to generate peptide bonds, and the peptide bonds are quickly combined with transpeptidase in thalli to inactivate the peptide bonds, bacteria cannot synthesize glycopeptides by virtue of the transpeptidase to build cell walls, bacterial cells can quickly become spheroids to be broken and dissolved, and the thalli are finally burst and die due to continuous permeation of water caused by loss of the cell walls.
In order to facilitate transportation and mixed drinking administration, amoxicillin is mainly soluble powder in veterinary drugs. The amoxicillin is quite stable to gastric acid, is absorbed by 74% -92% of single-stomach animals after oral administration, and the content in the gastrointestinal tract can influence the absorption rate of the amoxicillin but does not influence the absorption degree, so the amoxicillin can be administrated by mixed feeding. Although amoxicillin is rapidly absorbed orally, the maximum solubility of amoxicillin is very limited, and the solubility in 100ml water is only 0.1-0.2g, and during the dissolution process, calcium and magnesium ions in water are easily complexed to form precipitates.
At present, more amoxicillin soluble powder is a preparation formed by physically mixing amoxicillin and anhydrous glucose, and the amoxicillin soluble powder prepared by the method has poor water solubility, and the amoxicillin cannot be completely dissolved in water, so that the drug effect requirements of intensive culture and mixed feeding drug delivery cannot be met.
Some amoxicillin soluble powders have been disclosed, but their stability and solubility remain to be further improved.
Disclosure of Invention
The embodiment of the invention provides amoxicillin soluble powder and a preparation method thereof, and the amoxicillin soluble powder has higher solubility and better stability.
An amoxicillin soluble powder, which comprises the following components in parts by weight:
27-33 parts of amoxicillin;
1.8-2.2 parts of cosolvent; the cosolvent is one or more of polyvinylpyrrolidone, polyethylene glycol 6000, polyethylene glycol 4000 and polyethylene glycol 2000;
0.45-0.55 part of stabilizer; the stabilizer is selected from one or a combination of more of disodium ethylene diamine tetraacetate, sodium hexametaphosphate and sodium tripolyphosphate;
59-74 parts of a diluent; the diluent is selected from one or a combination of more of anhydrous glucose, lactose and water-soluble starch.
Further, the amoxicillin soluble powder comprises the following components in parts by weight:
28.5-31.5 parts of amoxicillin;
1.9-2.1 parts of cosolvent; the cosolvent is one or more of polyvinylpyrrolidone, polyethylene glycol 6000, polyethylene glycol 4000 and polyethylene glycol 2000;
0.48-0.53 part of stabilizer; the stabilizer is one or a combination of two of ethylene diamine tetraacetic acid, sodium hexametaphosphate and sodium tripolyphosphate;
63-70 parts of a diluent; the diluent is selected from one or a combination of more of anhydrous glucose, lactose and water-soluble starch.
Still further, the amoxicillin soluble powder comprises the following components in parts by weight:
30 parts of amoxicillin;
2 parts of a cosolvent; the cosolvent is one or more of polyvinylpyrrolidone, polyethylene glycol 6000, polyethylene glycol 4000 and polyethylene glycol 2000;
0.5 part of a stabilizer; the stabilizer is selected from one or a combination of more of ethylene diamine tetraacetic acid, sodium hexametaphosphate and sodium tripolyphosphate;
66.5 parts of a diluent; the diluent is selected from one or a combination of more of anhydrous glucose, lactose and water-soluble starch.
Still further, the amoxicillin soluble powder also comprises a pH regulator.
In some embodiments, the pH adjusting agent is present in an amount of 0.9 to 1.1 parts, such as 0.95 to 1.05 parts, per 100 parts of amoxicillin soluble powder.
The invention can adopt pH regulator commonly used in the field, such as one or more of citric acid, sodium dihydrogen phosphate, tartaric acid, meta-tartaric acid, fumaric acid and malic acid.
Further, the pH of a solution of said amoxicillin soluble powder in 1L of water per 0.2g is in the range of 3.6 to 6.1, optionally 4.1 to 5.9, specifically for example 4.2. It was found that it is more advantageous to increase the solubility and stability in this pH range.
Still further, the total amount of the amoxicillin soluble powder is 100 parts by weight.
Still further, the amoxicillin soluble powder contains 27-33 wt%, optionally 28.5-31.5 wt%, for example 30 wt% of amoxicillin.
Furthermore, the amoxicillin soluble powder contains 1.8-2.2 wt% of cosolvent, optionally 1.9-2.1 wt%, for example 2 wt%.
Furthermore, the amoxicillin soluble powder contains 0.45-0.55 wt% of stabilizer, optionally 0.48-0.53 wt%, such as 0.5 wt%.
Further, the amoxicillin soluble powder contains 59-74 wt% of diluent, optionally 63-70 wt%, such as 66.5 wt%.
Furthermore, in the amoxicillin soluble powder, the weight ratio of amoxicillin to the cosolvent to the stabilizer is 30:2: 0.5. This can improve the solubility and stability even more.
Further, the amoxicillin soluble powder is prepared by adopting dry granulation.
Dry granulation is a process in which the powders of the drug and the excipients are mixed uniformly, compressed into large tablets, plates or hard strips, and then pulverized into particles of the desired size.
The invention unexpectedly discovers that the amoxicillin soluble powder prepared by adopting the dry granulation method solves the problems of low amoxicillin solubility and poor stability, ensures the curative effect of the medicine, reduces the waste of materials, improves the production efficiency, reduces the energy consumption and reduces the environmental pollution.
On the other hand, the invention also provides a preparation method of the amoxicillin soluble powder, which comprises the following steps: firstly, carrying out dry granulation on amoxicillin, cosolvent, stabilizer and part of diluent, then crushing, and then mixing with the rest auxiliary materials.
In some embodiments, the portion of diluent refers to 40-60% of the total weight of the diluent, e.g., 40%, 45%, 50%, 55%, 60%.
In some embodiments, the pressure used during dry granulation is 4-8MPa, which can ensure that amoxicillin and the corresponding excipients are sufficiently close to each other to form intermolecular van der waals force, so that the raw and excipients are tightly combined, and the prepared amoxicillin soluble powder has better stability and solubility.
In some embodiments, the feeding speed is 35-65r/min and the rotating speed of the pressing wheel is 12-25r/min during dry granulation.
In some embodiments, a dry granulator conventional in the art is used.
In some embodiments, the granules prepared by dry granulation are crushed to 6-16 meshes, optionally 8-14 meshes, for example 12 meshes, which has the advantages that the prepared amoxicillin soluble powder has uniform granules and moderate granularity, can avoid the amoxicillin combined with corresponding auxiliary materials from being separated from the auxiliary materials, and can be easily mixed with the rest auxiliary materials after being crushed by a universal crusher, so that the prepared amoxicillin soluble powder has better solubility.
In some embodiments, the dry granulation machine used in dry granulation has the following parameter settings: the pressure of the pressure wheel is 4-8MPa, the feeding speed is 35-65r/min, the rotating speed of the pressure wheel is 12-25r/min, the crushing speed is 100-250r/min, and the particle size is set to be 8-14 meshes.
In some embodiments, the dry granulation machine used for dry granulation has the following parameter settings: the pressure of the pressing wheel is 8MPa, the feeding speed is 50r/min, the rotating speed of the pressing wheel is 23r/min, the crushing speed is 226r/min, and the particle size is 12 meshes.
In some embodiments, the granules prepared by dry granulation are milled using a universal mill, the parameters of which are set as follows: the rotating speed of the main shaft is 1500-; optionally, the rotating speed of the main shaft is 2000r/min, and the aperture of the sieve sheet is 0.7 mm.
In some embodiments, the preparation method of the amoxicillin soluble powder comprises the following steps:
1) mixing amoxicillin raw material, cosolvent, stabilizer and diluent with the total weight of 40-60% uniformly, granulating by a dry granulating machine, and then putting the obtained granules into a universal pulverizer to be pulverized;
wherein, the parameter setting of the dry-method granulator is as follows: the pressure of the pressure wheel is 4-8MPa, the feeding speed is 35-65r/min, the rotating speed of the pressure wheel is 12-25r/min, the crushing speed is 100-; setting parameters of the universal pulverizer: the rotating speed of the main shaft is 1500-;
2) and mixing the crushed amoxicillin mixture with a pH regulator, adding the rest diluent, and continuously and uniformly mixing to obtain the amoxicillin/diluent mixture.
The invention also provides amoxicillin soluble powder prepared by the method.
Drawings
FIG. 1 shows the result of the test of the stability of amoxicillin soluble powder in the aqueous solution in Experimental example 1.
Detailed Description
The following examples are intended to illustrate the invention, but are not intended to limit the scope of the invention. The examples do not specify particular techniques or conditions, and are to be construed in accordance with the description of the art in the literature or with the specification of the product. The reagents or instruments used are conventional products available from regular distributors, not indicated by the manufacturer.
Example 1
The amoxicillin soluble powder comprises the following raw materials in parts by weight per 100 parts of amoxicillin soluble powder: 30 parts of amoxicillin, 2 parts of polyvinylpyrrolidone, 0.5 part of disodium ethylenediamine tetraacetate, 1 part of citric acid and 66.5 parts of anhydrous glucose.
The preparation method comprises the following steps:
(1) setting parameters of a dry-process granulator: the pressure of a pressing wheel is 8MPa, the feeding speed is 50r/min, the rotating speed of the pressing wheel is 23r/min, the crushing speed is 226r/min, and the particle size is 12 meshes.
(2) Mixing 30 parts of amoxicillin raw material, 2 parts of polyvinylpyrrolidone, 0.5 part of disodium ethylene diamine tetraacetate and 36.5 parts of anhydrous glucose uniformly, granulating by a dry granulator, and crushing the obtained granules in a universal crusher. Setting parameters of the universal pulverizer: the rotating speed of the main shaft is 2000r/min, and the aperture of the sieve sheet is 0.7 mm.
(3) And mixing the crushed amoxicillin mixture with 1 part of citric acid and continuously and uniformly mixing 30 parts of anhydrous glucose to obtain the amoxicillin/citric acid/anhydrous glucose/glucose mixture.
Example 2
The amoxicillin soluble powder comprises the following raw materials in parts by weight per 100 parts of amoxicillin soluble powder: 30 parts of amoxicillin, 2 parts of polyethylene glycol 6000, 0.5 part of sodium hexametaphosphate, 1 part of sodium dihydrogen phosphate and 66.5 parts of anhydrous glucose.
The preparation process is as in example 1, with the difference that the dry granulator parameters are set: the pressure of a pressing wheel is 4MPa, the feeding speed is 35r/min, the rotating speed of the pressing wheel is 12r/min, the crushing speed is 100r/min, and the particle size is set to be 8 meshes.
Example 3
The amoxicillin soluble powder comprises the following raw materials in parts by weight per 100 parts of amoxicillin soluble powder: 33 parts of amoxicillin, 2.2 parts of polyethylene glycol 6000, 0.55 part of sodium hexametaphosphate, 1.1 part of sodium dihydrogen phosphate and 63.15 parts of anhydrous glucose.
The preparation method is as in example 1.
Example 4
The amoxicillin soluble powder comprises the following raw materials in parts by weight per 100 parts of amoxicillin soluble powder: 27 parts of amoxicillin, 1.8 parts of polyethylene glycol 4000, 0.45 part of sodium hexametaphosphate, 0.9 part of sodium dihydrogen phosphate and 69.85 parts of anhydrous glucose.
The preparation method is referred to example 1.
Example 5
An amoxicillin soluble powder has the same formula as the amoxicillin soluble powder in the example 1, and the preparation method is different from the example 1 only in the following parameter settings of a dry granulating machine: the pressure of the pressing wheel is 7MPa, the feeding speed is 65r/min, the rotating speed of the pressing wheel is 25r/min, the crushing speed is 250r/min, and the particle size is 14 meshes.
Example 6
An amoxicillin soluble powder has the same formula as the amoxicillin soluble powder in the example 1, and the preparation method is different from the example 1 only in the following parameter settings of a dry granulating machine: the pressure of the pressing wheel is 6MPa, the feeding speed is 40r/min, the rotating speed of the pressing wheel is 19r/min, the crushing speed is 110r/min, and the particle size is set to be 10 meshes.
Comparative example 1
An amoxicillin soluble powder has the same formula as the amoxicillin soluble powder in the example 1, and the difference is only in the preparation method. The preparation method of the comparative example does not comprise a dry granulation step and is prepared by only mixing the raw materials; the preparation method comprises the following steps: mixing 30 parts of amoxicillin raw material, 2 parts of polyvinylpyrrolidone, 0.5 part of disodium ethylene diamine tetraacetate and 36.5 parts of anhydrous glucose uniformly, and then putting the mixture into a universal pulverizer for pulverization. Setting parameters of the universal pulverizer: the rotating speed of the main shaft is 2000r/min, the aperture of the sieve sheet is 0.7mm, and then 1 part of citric acid and 30 parts of anhydrous glucose are added and continuously and uniformly mixed to obtain the glucose-free water-based screen printing ink.
Comparative example 2
An amoxicillin soluble powder, which is different from the amoxicillin soluble powder in example 1 only in that auxiliary materials are used: prepared according to the method of example 1, replacing polyvinylpyrrolidone with an equal amount of urea.
Comparative example 3
An amoxicillin soluble powder, which is different from the amoxicillin soluble powder in example 1 only in that auxiliary materials are used: prepared by replacing disodium edetate with an equal amount of calcium disodium edetate according to the method of example 1.
Comparative example 4
An amoxicillin soluble powder, which is different from the amoxicillin soluble powder in the embodiment 1 only in the parameters of the universal pulverizer in the step 2) in the preparation method: replacing the rotating speed of the main shaft of 2000r/min with the rotating speed of the main shaft of 1000 r/min; prepared according to the method of example 1 by replacing the sieve plate with 1.0mm in the aperture of 0.7 mm.
Comparative example 5
An amoxicillin soluble powder, which is different from the amoxicillin soluble powder in the embodiment 1 only in the parameters of the universal pulverizer in the step 2) in the preparation method: replacing the rotating speed of the main shaft of 2000r/min with the rotating speed of the main shaft of 3000 r/min; prepared according to the method of example 1 by replacing the sieve plate pore size of 0.7mm with 0.4 mm.
Experimental example 1
1. Solubility test
Experimental methods and conditions requirements: the commonly used dosage is as required according to the requirements of 'Chinese animal pharmacopoeia' 2015 edition 10% amoxicillin soluble powder [ usage and dosage ]: calculated by this product. Mixing and drinking: every 1L of water and 0.6g of chicken are continuously used for 3-5 days.
The specification of the amoxicillin soluble powder prepared in the embodiment 1 of the invention is 30%, so the sample weighing amount is calculated according to the requirements of 10% amoxicillin soluble powder [ usage and dosage ] in the 'Chinese animal pharmacopoeia' 2020 edition, and 0.2g (0.6 g/3 ═ 0.2g) of the amoxicillin soluble powder 30% of the product is taken for mixed drinking and dissolved in 1L of water.
Test samples:
sample a — amoxicillin soluble powder made from inventive example 1;
sample B — amoxicillin soluble powder made from comparative example 1;
sample C — amoxicillin soluble powder made from comparative example 2;
sample D — amoxicillin soluble powder made from comparative example 3;
sample E — amoxicillin soluble powder made from comparative example 4;
sample F — amoxicillin soluble powder made from comparative example 5.
The experimental method comprises the following steps: weighing each sample respectively, dissolving the sample in 1L of tap water with the temperature of 25 +/-2 ℃, stirring the sample by using an electric stirrer with the rotating speed of 270r/min until the powder of each sample is completely dissolved, and observing and recording the dissolution condition and the complete dissolution time. The corresponding sample weights and test results for each sample are shown in table 1.
As can be seen from Table 1, the amoxicillin soluble powder prepared by the method of example 1 of the present invention has a greatly improved solubility in water compared to the other 5 samples.
TABLE 1 results of solubility test of various amoxicillin soluble powders
2. Comparison of the stability of the aqueous solution content
The amoxicillin soluble powders prepared in comparative example 2 (sample C) and comparative example 3 (sample D) and the amoxicillin soluble powder prepared in example 1 of the present invention (hereinafter referred to as "this product") were selected and subjected to a stability control experiment of the aqueous solution content.
Experimental methods and conditions requirements: the experiment used standard hard water as the medium and simulated the actual temperature in the chicken coop at 30 ℃. Respectively weighing 0.2g of sample C, sample D and the product, adding 1000mL of hard water, stirring until the mixture is dissolved, placing the mixture in an environment with the temperature of 30 +/-2 ℃ in an open manner, measuring the content of the mixture for 2, 4, 6, 8, 10, 12, 16, 20 and 24 hours after preparation, comparing the content of the mixture with the content of the mixture for 0 hour after preparation, and recording the change (marked amount%) of the content. Preparation of standard hard water: the hardness is 0.342g/L calculated by calcium carbonate, and the preparation method comprises the following steps: 0.304g of anhydrous calcium chloride and 0.139g of magnesium chloride with crystal water are weighed into a volumetric flask of 1000mL, and dissolved and diluted to the scale with distilled water.
The amoxicillin content: the measurement is carried out according to high performance liquid chromatography (high performance liquid chromatography in the appendix of the first part of the 2015 edition of Chinese veterinary pharmacopoeia). The amoxicillin content is calculated by the external standard method according to the peak area, and the result is calculated by the percentage of the marked content. The results are shown in table 2 below and fig. 1.
TABLE 2 variation of the content of the aqueous solution of amoxicillin soluble powder (indicated amount%)
The results shown by table 2 and fig. 1 show that: the content stability of the amoxicillin soluble powder prepared by the process method is higher.
3. Stability of accelerated test
Experimental methods and conditions requirements: in order to examine the stability of the sample in the storage process, an accelerated experiment is carried out according to the relevant regulations of Chinese animal pharmacopoeia. Example 1 (product) a commercial package was simulated and packed in foil bags, accelerated tests were performed with the products of comparative example 2 (sample C) and comparative example 3 (sample D) at a temperature of 40 ℃ ± 2 ℃ and a relative humidity of 75% RH ± 5% RH, and the appearance and content of the samples were examined (results are indicated as percentage of the indicated content) by examining the properties, content, solubility after 1 month, 2 months, 3 months, 6 months of the accelerated tests and comparing with 0 month.
The results are shown in Table 3.
Table 3 shows the change of the characters, the content (%), and the degradation rate of the amoxicillin soluble powder after the accelerated experiment
The results show that: the amoxicillin soluble powder prepared by the invention has higher stability and solubility.
4. Experiment of drug effect
The following efficacy test was conducted using the amoxicillin soluble powder prepared by the method of the present invention of example 1 (this product) and the amoxicillin soluble powder prepared by the above comparative example 2 (sample C) and comparative example 3 (sample D) as samples.
(1) Experimental animals: 1200 sick chickens infected with escherichia coli through clinical diagnosis were randomly selected, and the weight was about 1 kg.
(2) The experimental method comprises the following steps: the 1200 sick chickens were randomly divided into three groups of 400 chickens; the three experimental groups were: 2 control groups (group 1 is sample C, group 2 is sample D) and 1 experimental group (group 3 is this product). Specific grouping and dosing regimens are shown in table 4:
TABLE 4 dosing regimen for groups of test sick chickens
After the treatment is started, the body change condition and the distribution of dead animals of the sick chickens are recorded daily, and the treatment effect is counted after 5 days of treatment, wherein:
and (4) invalidation: after 5 days, the symptoms of the sick chicken are not obviously changed and still keep the symptoms before treatment.
The method has the following advantages: after 5 days, the symptoms of the sick chicken are changed, and the symptoms are better than the effect before treatment.
And (3) curing: after 5 days, the symptoms disappear, and the sick chicken recover to be healthy. The number of which is included in the significant figures.
Symptoms at the end: after 5 days, the sick chicken still has certain symptoms, the symptom performance of the sick chicken is better than that of the sick chicken before treatment or without improvement, and the sick chicken is not cured. The numbers of which are already included in the numbers of the invalid and valid counts.
The results of the experiment are shown in table 5:
TABLE 5 therapeutic effect of different amoxicillin soluble powders on sick chicken
And (4) conclusion: the experimental results in the table 5 show that the treatment effect of the amoxicillin soluble powder prepared by the invention on the sick chicken is higher than that of a control group in the effective number and the cure rate of the amoxicillin soluble powder prepared by the invention than that of two products sold in the market. Therefore, the amoxicillin soluble powder has better treatment effect on chicken pathogenic bacteria infection.
Although the invention has been described in detail hereinabove with respect to a general description and specific embodiments thereof, it will be apparent to those skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (10)
1. An amoxicillin soluble powder, which comprises the following components in parts by weight:
27-33 parts of amoxicillin;
1.8-2.2 parts of cosolvent; the cosolvent is one or more of polyvinylpyrrolidone, polyethylene glycol 6000, polyethylene glycol 4000 and polyethylene glycol 2000;
0.45-0.55 part of stabilizer; the stabilizer is selected from one or a combination of more of ethylene diamine tetraacetic acid, sodium hexametaphosphate and sodium tripolyphosphate;
59-74 parts of a diluent; the diluent is selected from one or a combination of more of anhydrous glucose, lactose and water-soluble starch;
a pH adjusting agent; the pH value of a solution formed by every 0.2g of amoxicillin soluble powder in 1L of water is 3.6-6.1;
the preparation method of the amoxicillin soluble powder comprises the following steps:
1) mixing amoxicillin raw material, cosolvent, stabilizer and diluent with the total weight of 40-60% uniformly, granulating by a dry granulating machine, and then putting the obtained granules into a universal pulverizer to be pulverized;
wherein, the parameter setting of the dry-method granulator is as follows: the pressure of the pressure wheel is 4-8MPa, the feeding speed is 35-65r/min, the rotating speed of the pressure wheel is 12-25r/min, the crushing speed is 100-250r/min, and the particle size is set to be 8-14 meshes; setting parameters of the universal pulverizer: the rotating speed of the main shaft is 1500-;
2) and mixing the crushed amoxicillin mixture with a pH regulator, adding the rest diluent, and continuously and uniformly mixing to obtain the amoxicillin/diluent mixture.
2. The amoxicillin soluble powder of claim 1, comprising in parts by weight:
28.5-31.5 parts of amoxicillin;
1.9-2.1 parts of cosolvent; the cosolvent is one or more of polyvinylpyrrolidone, polyethylene glycol 6000, polyethylene glycol 4000 and polyethylene glycol 2000;
0.48-0.53 part of stabilizer; the stabilizer is one or a combination of two of ethylene diamine tetraacetic acid, sodium hexametaphosphate and sodium tripolyphosphate;
63-70 parts of a diluent; the diluent is selected from one or a combination of more of anhydrous glucose, lactose and water-soluble starch.
3. The amoxicillin soluble powder of claim 1, comprising in parts by weight:
30 parts of amoxicillin;
2 parts of a cosolvent; the cosolvent is one or more of polyvinylpyrrolidone, polyethylene glycol 6000, polyethylene glycol 4000 and polyethylene glycol 2000;
0.5 part of a stabilizer; the stabilizer is selected from one or a combination of more of disodium ethylene diamine tetraacetate, sodium hexametaphosphate and sodium tripolyphosphate;
66.5 parts of a diluent; the diluent is selected from one or a combination of more of anhydrous glucose, lactose and water-soluble starch.
4. The amoxicillin soluble powder of claim 1, wherein per 100 parts by weight of amoxicillin soluble powder, the raw materials are: 30 parts of amoxicillin, 2 parts of polyvinylpyrrolidone, 0.5 part of disodium ethylene diamine tetraacetate, 1 part of citric acid and 66.5 parts of anhydrous glucose.
5. An amoxicillin soluble powder according to claim 1 having a pH of 4.1 to 5.9 per 0.2g of solution in 1L of water.
6. An amoxicillin soluble powder according to claim 1 having a pH of 4.2 per 0.2g of solution in 1L of water.
7. An amoxicillin soluble powder according to any one of claims 1-4 in a total amount of 100 parts by weight.
8. The amoxicillin soluble powder according to any one of claims 1-4 and 6, wherein the dry granulation machine has the following parameters: the pressure of the pressing wheel is 8MPa, the feeding speed is 50r/min, the rotating speed of the pressing wheel is 23r/min, the crushing speed is 226r/min, and the particle size is 12 meshes; setting parameters of the universal pulverizer: the rotating speed of the main shaft is 2000r/min, and the aperture of the sieve sheet is 0.7 mm.
9. A process for the preparation of an amoxycillin soluble powder as claimed in any one of claims 1 to 8, which comprises
1) Mixing amoxicillin raw material, cosolvent, stabilizer and diluent with the total weight of 40-60% uniformly, granulating by a dry granulating machine, and then putting the obtained granules into a universal pulverizer to be pulverized;
wherein, the parameter setting of the dry-method granulator is as follows: the pressure of the pressure wheel is 4-8MPa, the feeding speed is 35-65r/min, the rotating speed of the pressure wheel is 12-25r/min, the crushing speed is 100-250r/min, and the particle size is set to be 8-14 meshes; setting parameters of the universal pulverizer: the rotation speed of the main shaft is 1500-2500r/min, and the aperture of the sieve sheet is 0.5-0.8 mm;
2) and mixing the crushed amoxicillin mixture with a pH regulator, adding the rest diluent, and continuously and uniformly mixing to obtain the amoxicillin/diluent mixture.
10. The manufacturing method according to claim 9, wherein the dry granulator has parameter settings of: the pressure of the pressing wheel is 8MPa, the feeding speed is 50r/min, the rotating speed of the pressing wheel is 23r/min, the crushing speed is 226r/min, and the particle size is 12 meshes; setting parameters of the universal pulverizer: the rotating speed of the main shaft is 2000r/min, and the aperture of the sieve sheet is 0.7 mm.
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| CN114886854B (en) * | 2022-05-19 | 2024-02-06 | 中国农业科学院上海兽医研究所 | Soluble cimetidine powder and preparation method thereof |
| CN117379378A (en) * | 2023-12-07 | 2024-01-12 | 山东金瑞生物科技有限公司 | Compound amoxicillin soluble powder for livestock and preparation process thereof |
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| CN100402030C (en) * | 2006-01-05 | 2008-07-16 | 珠海联邦制药股份有限公司 | Pharmaceutical composition containing amoxicillin and preparation method thereof |
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| CN108670957A (en) * | 2018-07-05 | 2018-10-19 | 河南牧翔动物药业有限公司 | One kind acidification amoxicillin soluble powder for animals and preparation method thereof |
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