CN112587563A - Antibacterial Chinese and western medicine powder for amoxicillin and scutellaria baicalensis for livestock and preparation method thereof - Google Patents
Antibacterial Chinese and western medicine powder for amoxicillin and scutellaria baicalensis for livestock and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an amoxicillin and scutellaria baicalensis antibacterial Chinese and western medicine powder for livestock and a preparation method thereof, and the amoxicillin and scutellaria baicalensis antibacterial Chinese and western medicine powder comprises the following components in parts by mass: 10-20 parts of active ingredients, 60-70 parts of moisture absorbent, 5-10 parts of filler and 1-3 parts of solubilizer; the active ingredients comprise amoxicillin and scutellaria baicalensis extracts in a mass ratio of 1: 1-10: 1; the solubilizer consists of sodium p-toluenesulfonate and tea saponin. The invention combines amoxicillin and scutellaria baicalensis extracts to prepare the Chinese and western medicine preparation, and the drug effect can be enhanced after the combination of the amoxicillin and the scutellaria baicalensis extracts, thereby avoiding the problem of bacterial drug resistance caused by long-term use of a large amount of antibiotics in the culture production. The medicament formulation developed by the invention is powder, can be administered by mixing materials, can reduce the stress response of animals, can be administered in batches, reduces the administration workload and the labor cost, and the produced powder has low relative moisture absorption rate, good stability, improved medicament solubility and improved bioavailability by selecting auxiliary materials.
Description
Technical Field
The invention belongs to the technical field of prevention and treatment of bacterial diseases of livestock and poultry, and particularly relates to amoxicillin and scutellaria baicalensis bacteriostatic Chinese and western medicine powder for livestock and a preparation method thereof.
Background
Bacterial diseases have been a major problem that plagues and limits the growth of the aquaculture industry. Not only harms the economic benefit of farmers, but also harms the sanitation and safety of animal-derived foods. The amoxicillin has strong bactericidal effect as a broad-spectrum antibacterial drug, and in order to improve the antibacterial effect, many scholars combine the amoxicillin with western medicines such as clavulanic acid, colistin sulfate and the like, so that the dosage of the amoxicillin can be reduced and the same or better effect can be achieved after the combined medicine is used.
In recent years, multiple studies show that the scutellaria baicalensis has the effects of resisting bacteria, viruses, tumors and the like, so that the scutellaria baicalensis is more and more extensive clinically, baicalin is used as one of main effective components of the scutellaria baicalensis, has wide pharmacological action, can reduce the generation of drug-resistant bacteria when being used for clinical treatment in the antibacterial aspect, solves the problem of veterinary drug residue in the aspect of animal-derived food safety, and has long-term use value.
Therefore, the invention combines the antibacterial western medicine amoxicillin and the antibacterial traditional Chinese medicine scutellaria, the drug effects of the two medicines achieve the synergistic effect, and the drug effect is more obvious.
Disclosure of Invention
The invention aims at the defects of the current livestock bacterial disease medicine. Provides an amoxicillin and scutellaria baicalensis antibacterial Chinese and western medicine powder for livestock and a preparation method thereof. The invention combines amoxicillin and scutellaria baicalensis extracts to prepare the Chinese and western medicine preparation, the drug effect can be enhanced after the combined action of the amoxicillin and the scutellaria baicalensis extracts, the problem of bacterial drug resistance caused by long-term use of a large amount of antibiotics in culture production is avoided, the risk of safe production of food animals is reduced, and the food animals are more in line with green culture. The preparation formulation developed by the invention is a powder formulation, can be administered by mixing materials, can reduce the stress response of animals, can be administered in batches, reduces the administration workload and the labor cost, and the stability of the produced powder is good, the drug solubility is improved and the bioavailability is improved by selecting auxiliary materials.
In order to achieve the purpose, the invention is realized by the following technical scheme:
the antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 10-20 parts of active ingredients, 60-70 parts of moisture absorbent, 5-10 parts of filler and 1-3 parts of solubilizer; the active ingredients comprise amoxicillin and scutellaria baicalensis extracts in a mass ratio of 1: 1-10: 1; the solubilizer consists of sucrose stearate glyceride and tea saponin.
Further, the moisture absorbent is one or more of glucose, sucrose, corn starch and tapioca starch mixed with sodium polyacrylate.
Preferably, the moisture absorbent consists of glucose and sodium polyacrylate. The mass ratio of the glucose to the sodium polyacrylate is 10-20: 1.
Further, the filler is composed of cyclodextrin and hydroxypropyl distarch phosphate. Preferably, the mass ratio of the cyclodextrin to the hydroxypropyl distarch phosphate is 3-5: 1.
Preferably, the solubilizer consists of sodium hard p-toluenesulfonate and tea saponin in a mass ratio of 1: 1-3.
The invention also provides a preparation method of the antibacterial Chinese and western medicine powder for livestock, which comprises the following steps: respectively pulverizing amoxicillin and radix scutellariae extracts to 60-100 meshes, and uniformly mixing to obtain active ingredients; and uniformly mixing the active ingredients, the hygroscopic agent, the filling agent and the solubilizer to obtain the amoxicillin and scutellaria baicalensis extract powder preparation.
Compared with the prior art, the invention has the advantages and beneficial effects that:
1. the invention combines amoxicillin and scutellaria baicalensis extracts to prepare the Chinese and western medicine preparation, the drug effect can be enhanced after the combined action of the amoxicillin and the scutellaria baicalensis extracts, the problem of bacterial drug resistance caused by long-term use of a large amount of antibiotics in culture production is avoided, the risk of safe production of food animals is reduced, and the food animals are more in line with green culture. The medicament prepared by the invention is a powder preparation, can be administered by mixing materials, can reduce the stress response of animals, can be administered in batches, reduces the administration workload and the labor cost, and the produced powder has lower relative hygroscopicity, good stability, improved medicament solubility and improved bioavailability by selecting auxiliary materials.
2. The solubilizing agent consisting of sodium p-toluenesulfonate and tea saponin is added, so that the solubility and the dissolution rate of the amoxicillin and scutellaria baicalensis extracts can be improved, and the defects of poor water solubility and low bioavailability of the amoxicillin can be effectively overcome; the added tea saponin also has antibacterial and bacteriostatic effects, and improves the antibacterial effect of the medicine.
3. The moisture absorbent used in the invention can ensure that the moisture absorption degree of the powder medicine is lower, the stability is better, and the quality guarantee period is prolonged; the filler is composed of cyclodextrin and hydroxypropyl distarch phosphate, and has high dispersion degree and good fluidity, thereby improving the stability and processing performance of the medicine.
4. The amoxicillin/scutellaria baicalensis extract Chinese and western powder prepared by the invention has the characteristics of good dispersibility, quick absorption, quick response, easy carrying, convenient taking and the like, has the advantages of high solubility, low relative hygroscopicity, good stability, high bioavailability and the like, can be used for treating respiratory tract and digestive tract diseases of livestock and poultry such as pigs, chickens and the like mainly caused by bacterial infection, and has remarkable treatment effect and less side effect.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments. It should be emphasized that the following description is merely exemplary in nature and is not intended to limit the scope of the invention or its application.
In-vitro combined drug sensitivity test of amoxicillin and scutellaria baicalensis extracts
1. Raw materials: amoxicillin, scutellaria baicalensis extract (the scutellaria baicalensis extract is a commercially available product); the strain is as follows: staphylococcus aureus 6 strain, Staphylococcus aureus porcine 3 strain, and Staphylococcus aureus ATCC-25213.
2. Serum nutrient agar medium: preparing according to the specification of nutrient agar, sterilizing at 121 deg.C under high pressure for 15 min, cooling to about 50 deg.C, adding 5% of sterilized calf serum (filtered by disposable sterile filter), shaking, pouring into 90 mm culture dish, standing for 15 min, turning over, placing in constant temperature incubator overnight, determining no pollution, and placing in 4 deg.C refrigerator for use.
3. Preparing a bacterial liquid: culturing various strains for 8-12 h by rejuvenation, culturing for 12 h by cutting plate again, separating single colony, selecting partial colony in sterilized normal saline, counting by McLee's turbidimetry, diluting bacterial liquid to 3 × 108CFU/mL, diluted with the corresponding broth to a final concentration of 1X 106 CFU/mL。
4. In vitro combined drug sensitivity test: the experiments were performed with reference to the method recommended by CLSI. The single medicine is used for minimum bacteriostasisConcentration (MIC) test results were based on a 7 x 7 combination of 8-, 4-, 2-, 1-, 1/2-, 1/4-and 1/8-fold MIC design on broth dilution checkerboard. Because the solubility of the radix Scutellariae extract is limited, when the 8-fold MIC value of the radix Scutellariae extract is higher than 5 × 10 in the combined drug sensitivity test4mu.g/mL, 5X 104mu.g/mL is the maximum concentration, and then diluted by a multiple dilution method to 7 concentrations. And (3) diluting the amoxicillin and the scutellaria baicalensis extract by using a proper broth to reach the medicine concentration required by the test for later use. 1-8 wells of rows A-h of a 96-well plate were selected as test areas, and Scutellariae radix extract was diluted with broth to 7 concentrations and added in a column from the 7 th column to the 1 st column from low to high concentrations, 50. mu.L per well, and the 8 th column was used as a single drug control for amoxicillin. The amoxicillin is diluted to 7 concentrations with broth, and is added from the G row to the A row in a horizontal row from low to high, 50 μ L per well, and the H row is used as a single drug control of the scutellaria baicalensis extract. And (3) adding 100 mu L of liquid medicine into each hole of the single-medicine control holes of the amoxicillin and the scutellaria baicalensis extracts. Then 100. mu.L of the prepared bacterial suspension was added to each well to which the liquid medicine was added, and 200. mu.L of the bacterial suspension was added to the 8 th well of the H row to serve as a positive control well. In column 12, 200. mu.L of broth was added as a negative control. And covering a cover after the completion, marking, putting the 96-well plate in a 37 ℃ constant temperature incubator for culturing for 18-24 h, and observing and recording the result. Each plate was tested for in vitro combined susceptibility of two drugs to one strain. The results of the bacteriostatic test are shown in table 1.
Table 1: results of amoxicillin and scutellaria baicalensis extract bacteriostasis test
From the table 1, the minimum inhibitory concentration of amoxicillin and baicalin to salmonella in the combined use is reduced by more than one time than that of the two medicines when used alone, which indicates that the bacteriostatic effect of the single medicine can be achieved by reducing the dosage of the medicines by at least half in the combined use of the two medicines, thereby reducing the use of antibiotics and delaying the generation of drug resistance of bacteria while achieving the effect.
Example 1
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 8 parts of amoxicillin, 8 parts of scutellaria baicalensis extract, 50 parts of glucose, 5 parts of sodium polyacrylate, 6 parts of cyclodextrin, 2 parts of hydroxypropyl distarch phosphate, 1 part of sodium p-toluenesulfonate and 2 parts of tea saponin.
Example 2
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 5 parts of amoxicillin, 5 parts of scutellaria baicalensis extract, 40 parts of sucrose, 3 parts of sodium polyacrylate, 5 parts of cyclodextrin, 2 parts of hydroxypropyl distarch phosphate, 1 part of sodium p-toluenesulfonate and 1.5 parts of tea saponin.
Example 3
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 10 parts of amoxicillin, 5 parts of scutellaria baicalensis extract, 50 parts of corn starch, 5 parts of sodium polyacrylate, 5 parts of cyclodextrin, 1 part of hydroxypropyl distarch phosphate, 0.5 part of sodium p-toluenesulfonate and 1.5 parts of tea saponin.
Example 4
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 12 parts of amoxicillin, 6 parts of scutellaria baicalensis extract, 60 parts of cassava starch, 5 parts of sodium polyacrylate, 4 parts of cyclodextrin, 2 parts of hydroxypropyl distarch phosphate, 1 part of sodium p-toluenesulfonate and 2 parts of tea saponin.
Example 5
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 8 parts of amoxicillin, 8 parts of scutellaria baicalensis extract, 30 parts of glucose, 20 parts of corn starch, 5 parts of sodium polyacrylate, 4 parts of cyclodextrin, 1 part of hydroxypropyl distarch phosphate, 1 part of sodium p-toluenesulfonate and 2 parts of tea saponin.
Comparative example 1
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 8 parts of amoxicillin, 8 parts of scutellaria baicalensis extract, 55 parts of glucose, 6 parts of cyclodextrin, 1 part of sodium p-toluenesulfonate and 2 parts of tea saponin.
Comparative example 2
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 8 parts of amoxicillin, 8 parts of scutellaria baicalensis extract, 50 parts of glucose, 5 parts of sodium polyacrylate, 6 parts of cyclodextrin, 1 part of sodium p-toluenesulfonate and 1 part of tea saponin.
Comparative example 3
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 8 parts of amoxicillin, 8 parts of scutellaria baicalensis extract, 50 parts of glucose, 5 parts of sodium polyacrylate, 3 parts of cyclodextrin, 1 part of hydroxypropyl distarch phosphate and 1 part of sodium toluenesulfonate.
Comparative example 4
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 8 parts of amoxicillin, 8 parts of scutellaria baicalensis extract, 50 parts of glucose, 5 parts of sodium polyacrylate, 6 parts of cyclodextrin, 1 part of hydroxypropyl distarch phosphate and 2 parts of tea saponin.
Comparative example 5
The antibacterial Chinese and western medicine powder for the livestock comprises the following components in parts by mass: 8 parts of amoxicillin, 8 parts of scutellaria baicalensis extract, 50 parts of glucose and 3 parts of cyclodextrin.
The powders of examples 1 to 5 and comparative examples 1 to 5 were selected and the moisture absorption rate, flowability (expressed as the average value of angle of repose) and solubility of the components were measured.
1 determination of moisture absorption Rate
Placing a glass dryer with the supersaturated sodium chloride solution at the bottom at room temperature for 48 h to balance, wherein the relative humidity in the dryer is 75%, placing a sample dried to the constant weight of about 1 g at the bottom of a 5 mL flat weighing bottle with the dried constant weight, shaking gently to distribute the sample uniformly, precisely weighing, placing the sample in the dryer with the supersaturated sodium chloride solution (the weighing bottle is uncovered), and weighing after 24 h (n = 3).
The percent moisture absorption was calculated as follows:
percent moisture absorption% = (weight after moisture absorption-weight before moisture absorption)/weight before moisture absorption × 100%
2.2 determination of the angle of repose
2.2.1 measuring the angle of repose by adopting a fixed funnel method, fixing a funnel at the height of 3 cm above coordinate paper (the paper is placed on a horizontal table), adding materials from the funnel until the top of the formed stacking cone is just contacted with the bottom of the funnel, measuring the diameter of the cone, and calculating the angle of repose by taking the ratio of the height of the bottom of the funnel to the radius of the cone as a tangent value.
The amoxicillin, the scutellaria baicalensis extract and various auxiliary materials are firstly placed in a blast constant-temperature oven at 60 ℃ for drying for 2 hours, and then the medicines and the auxiliary materials are sieved by a sieve with 80 meshes according to the related regulations of powder in Chinese veterinary pharmacopoeia.
3 determination of solubility
The solubility was determined by the shaker method:
putting 50 mL of medium into a 100mL conical flask with a plug, adding excessive amoxicillin and auxiliary materials and radix scutellariae extract and auxiliary materials, and carrying out ultrasonic treatment for 15 min to fully wet the medicine in the medium. Sealing the supersaturated solution of different media, placing in a constant temperature gas bath oscillator at 37 ℃, horizontally oscillating at 100 rpm for 72 h, sampling after 1 h, 2 h, 3 h, 10 h, 24 h, 48 h and 72 h, filtering with a 0.45 μm microporous filter membrane under heat preservation, discarding the primary filtrate, taking a proper amount of the subsequent filtrate, diluting, injecting 20 μ L, and performing content determination by high performance liquid chromatography at a detection wavelength of 254 nm to obtain the equilibrium solubility.
The results are as follows:
TABLE 2 moisture absorption rate, flowability (expressed as an average value of angle of repose), and solubility measurement results
| Rate of moisture absorption | Mean angle of repose ° | Solubility C (g/100 mL) | |
| Example 1 | 2.28±0.03 | 43.18 | 1.232 |
| Example 2 | 3.15±0.13 | 44.25 | 1.034 |
| Example 3 | 6.34±0.28 | 44.87 | 0.925 |
| Example 4 | 6.89±0.06 | 45.16 | 1.212 |
| Example 5 | 5.58±0.97 | 45.93 | 1.225 |
| Comparative example 1 | 2.59±0.97 | 46.93 | 1.232 |
| Comparative example 2 | 2.38±0.37 | 47.31 | 1.012 |
| Comparative example 3 | 2.45±0.45 | 50.44 | 0.912 |
| Comparative example 4 | 2.43±0.61 | 53.24 | 0.643 |
| Comparative example 5 | 2.62±0.31 | 56.24 | 0.537 |
As can be seen from Table two, in examples 1 to 5, compared with the results of moisture absorption rate obtained without adding sodium polyacrylate to the moisture absorbent (comparative example 1 and comparative example 5), the moisture absorption rate of glucose and sodium polyacrylate is significantly lower than that of corn starch and tapioca starch, and the moisture absorption rate can be significantly reduced by adding polyacrylamide.
Examples 1-5 are compared to the results for the angle of repose without hydroxypropyl distarch phosphate (compare comparative examples 2 and 5), which are significantly greater than the examples, and the average value for the angle of repose of the dust is minimal.
The solubility of the powders of examples 1-5 is equivalent to that of the powders without additives such as sodium p-toluenesulfonate or tea saponin (comparative examples 3, 4 and 5), and the solubility of the comparative examples is obviously lower, which shows that the addition of sodium p-toluenesulfonate or tea saponin to the powders has a solubilizing effect, and secondly, the synergistic solubilizing effect of sodium p-toluenesulfonate and tea saponin can be seen from the comparative examples 3, 4 and 5 and the example 1.
The foregoing is a more detailed description of the invention in connection with specific/preferred embodiments and is not intended to limit the practice of the invention to those descriptions. It will be apparent to those skilled in the art that various substitutions and modifications can be made to the described embodiments without departing from the spirit of the invention, and such substitutions and modifications are to be considered as within the scope of the invention.
Claims (8)
1. A bacteriostatic Chinese and western medicine compound powder for livestock is characterized in that: the composition comprises the following components in parts by mass: 10-20 parts of active ingredients, 60-70 parts of moisture absorbent, 5-10 parts of filler and 1-3 parts of solubilizer; the active ingredients comprise amoxicillin and scutellaria baicalensis extracts in a mass ratio of 1: 1-10: 1; the solubilizer consists of sodium p-toluenesulfonate and tea saponin.
2. The bacteriostatic Chinese-western medicine compound powder for the livestock according to claim 1, which is characterized in that: the moisture absorbent is one or more of glucose, sucrose, corn starch and tapioca starch mixed with sodium polyacrylate.
3. Bacteriostatic Chinese and Western medicine powder for livestock according to claim 2, characterized in that: the moisture absorbent consists of glucose and sodium polyacrylate.
4. The bacteriostatic Chinese-western medicine compound powder for the livestock according to claim 3, which is characterized in that: the mass ratio of glucose to sodium polyacrylate in the hygroscopic agent is 10-20: 1.
5. The bacteriostatic Chinese-western medicine compound powder for the livestock according to claim 1, which is characterized in that: the filler is composed of cyclodextrin and hydroxypropyl distarch phosphate.
6. The bacteriostatic Chinese-western medicine compound powder for the livestock according to claim 5, which is characterized in that: the mass ratio of the cyclodextrin to the hydroxypropyl distarch phosphate is 3-5: 1.
7. The bacteriostatic Chinese-western medicine compound powder for the livestock according to claim 1, which is characterized in that: the solubilizer consists of sodium p-toluenesulfonate and tea saponin in a mass ratio of 1: 1-3.
8. The preparation method of the bacteriostatic Chinese-western medicine compound powder for livestock as claimed in any one of claims 1-7, which is characterized in that: the method comprises the following steps: respectively pulverizing amoxicillin and radix scutellariae extracts to 60-100 meshes, and uniformly mixing to obtain active ingredients; and uniformly mixing the active ingredients, the hygroscopic agent, the filling agent and the solubilizer to obtain the amoxicillin and scutellaria baicalensis extract powder preparation.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114569560A (en) * | 2022-03-25 | 2022-06-03 | 江西利德菲生物药业有限公司 | Amoxicillin soluble powder with high dissolubility and preparation method thereof |
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