CN113018324A - Application of dipsacus asperoides extract, composite antibacterial composition, preparation method of composite antibacterial composition and composite antibacterial preparation - Google Patents
Application of dipsacus asperoides extract, composite antibacterial composition, preparation method of composite antibacterial composition and composite antibacterial preparation Download PDFInfo
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- CN113018324A CN113018324A CN202110338437.6A CN202110338437A CN113018324A CN 113018324 A CN113018324 A CN 113018324A CN 202110338437 A CN202110338437 A CN 202110338437A CN 113018324 A CN113018324 A CN 113018324A
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- florfenicol
- extract
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- dipsacus asperoides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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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
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- Agricultural Chemicals And Associated Chemicals (AREA)
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Abstract
The invention relates to the technical field of animal antibacterial agents, and particularly relates to application of a dipsacus asperoides extract, a composite antibacterial composition, a preparation method of the composite antibacterial composition and a composite antibacterial preparation. The invention provides an application of a dipsacus asperoides extract in preparation of a florfenicol synergist. The dipsacus root extract and the florfenicol are compounded, so that the blood concentration and the bioavailability of the florfenicol can be further improved, and the antibacterial effect of the florfenicol is further improved.
Description
Technical Field
The invention relates to the technical field of animal antibacterial agents, and particularly relates to application of a dipsacus asperoides extract, a composite antibacterial composition, a preparation method of the composite antibacterial composition and a composite antibacterial preparation.
Background
Florfenicol is a synthetic monofluoro derivative of thiamphenicol, is white or grey white crystalline powder, is an animal special antibacterial drug, is used for treating bacterial diseases of pigs, chickens and fish caused by sensitive bacteria, and particularly has obvious curative effects on respiratory system infection and intestinal infection. The florfenicol is quick to absorb orally, wide in distribution, long in half-life period, high in blood concentration and long in maintenance time, but can be compounded with other medicines to form a composition in order to further improve the antibacterial effect of the florfenicol.
In view of this, the invention is particularly proposed.
Disclosure of Invention
The invention aims to provide application of a dipsacus asperoides extract, a composite antibacterial composition, a preparation method thereof and a composite antibacterial preparation. The embodiment of the invention discovers that the blood concentration and the bioavailability of the florfenicol can be further improved by compounding the dipsacus asperoides extract and the florfenicol, so that the antibacterial effect of the florfenicol is further improved.
The invention is realized by the following steps:
in a first aspect, the invention provides an application of a dipsacus asperoides extract in preparation of a florfenicol synergist.
In an alternative embodiment, the teasel root extract is a mixture of aqueous and alcoholic extracts of teasel root.
In an alternative embodiment, the potentiator is a potentiator that achieves any one of the following: (1) the blood concentration of the florfenicol is improved; (2) the bioavailability of the florfenicol is improved; (3) the antibacterial effect of the florfenicol is improved.
In a second aspect, the invention provides a composite antibacterial composition, and the active ingredients comprise 1-20 parts of florfenicol and 5-10 parts of dipsacus asperoides extract in parts by weight.
In an alternative embodiment, the active ingredients comprise 5 to 20 parts of florfenicol and 5 to 10 parts of dipsacus asperoides extract by weight;
preferably, the dipsacus asperoides extract is a mixture of aqueous and alcoholic extracts of dipsacus asperoides;
preferably, the mass percentage of the teasel saponin VI in the teasel root extract is not less than 6.6%.
In a third aspect, the present invention provides a method for preparing a composite antibacterial composition according to the previous embodiment, including: mixing florfenicol and radix Dipsaci extract at a certain ratio.
In an alternative embodiment, the preparation of the extract of dipsacus asperoides comprises: mixing radix Dipsaci material with alcohol-water solution at a mass ratio of 1:6-10, heating, reflux extracting at least once, mixing extractive solutions, and concentrating;
preferably, the time for each extraction is 1.5 hours or more;
preferably, the mass of the concentrated extract is one third to two thirds of the mass of the teasel root raw material;
preferably, the alcohol-water solution is an alcohol solution with the mass percent of alcohol of 60-80%;
preferably, the alcohol is a monohydric alcohol, preferably ethanol.
In a fourth aspect, the invention provides a compound antibacterial preparation, which comprises, by weight, 1-20 parts of florfenicol, 5-10 parts of dipsacus asperoides extract and 70-90 parts of pharmaceutically acceptable auxiliary materials.
In an optional embodiment, the raw materials comprise 5-20 parts of florfenicol, 5-10 parts of dipsacus asperoides extract and 70-90 parts of pharmaceutically acceptable auxiliary materials in parts by weight.
In alternative embodiments, the complex antimicrobial formulation is a solid formulation or a liquid formulation;
the solid preparation comprises granules, tablets or powder;
the liquid formulation includes: suspensions, mixtures or emulsions.
The invention has the following beneficial effects: the dipsacus asperoides extract provided by the embodiment of the invention can improve the blood concentration of florfenicol, so as to improve the bioavailability of florfenicol and finally improve the antibacterial effect of florfenicol.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 is a standard curve chart provided in Experimental example 1 of the present invention;
FIG. 2 is a typical chromatogram for florfenicol in plasma provided in Experimental example 1 of the present invention;
fig. 3 is a blood concentration-time curve provided in experimental example 1 of the present invention;
FIG. 4 is a graph showing the results of the relative expression amounts of CYP3A37, MDR1mRNA and CXR mRNA in chicken liver, which are provided in Experimental example 2 of the present invention;
FIG. 5 is a graph showing the results of the relative expression amounts of CYP3A37, MDR1mRNA and CXR mRNA in chicken jejunum, which are provided in Experimental example 2 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The embodiment of the invention provides an application of a dipsacus asperoides extract in preparation of a synergist of florfenicol, wherein the dipsacus asperoides extract can improve the blood concentration of the florfenicol, increase the absorption speed of the florfenicol, reduce the metabolism rate of the florfenicol in vivo, improve the bioavailability of the florfenicol, and finally improve the antibacterial effect of the florfenicol.
Therefore, the embodiment of the invention also provides a composite antibacterial composition, which comprises 1-20 parts of florfenicol and 5-10 parts of dipsacus asperoides extract as active ingredients or comprises 5-20 parts of florfenicol and 5-10 parts of dipsacus asperoides extract as active ingredients in parts by weight; or the active ingredients are 5-20 parts of florfenicol and 5-10 parts of dipsacus asperoides extract; the synergistic effect of the dipsacus asperoides extract on florfenicol can be further ensured by adopting the mixture ratio.
Further, the teasel root extract is a mixture of a teasel root aqueous extract and a teasel root alcohol extract, the mass percentage of the saponins VI of the teasel roots in the teasel root extract is ≧ 6.6%, and the teasel root extract can be prepared by self or purchased directly from manufacturers, such as Guanghan Sanxingdong plant pharmaceutical factory.
The preparation method of the composite antibacterial composition comprises the following steps: mixing florfenicol and radix Dipsaci extract at a certain ratio.
Wherein, the preparation of the dipsacus root extract comprises the following steps: mixing radix Dipsaci material with alcohol-water solution at a mass ratio of 1:6-10, heating, reflux extracting at least once, mixing extractive solutions, and concentrating; wherein, the extraction times can be 1 time, 2 times, 3 times or even more, and the extraction time is more than 1.5 hours each time; for example, 2 hours, 3 hours, etc. may be used. The mass of the concentrated extract is one third to two thirds of the mass of the raw material of the teasel; the alcohol-water solution is an alcohol solution with the mass percent of alcohol of 60-80%; the alcohol is a monohydric alcohol, preferably ethanol. As the alcohol, monohydric alcohols such as methanol and propanol may be used in addition to ethanol.
The radix Dipsaci extract can also be prepared by extracting radix Dipsaci with water or alcohol to obtain primary extracts, and mixing the two primary extracts.
Further, the embodiment of the invention also provides a compound antibacterial preparation, which comprises, by weight, 1-20 parts of florfenicol, 5-10 parts of dipsacus asperoides extract and 70-90 parts of pharmaceutically acceptable auxiliary materials, or comprises 5-20 parts of florfenicol, 5-10 parts of dipsacus asperoides extract and 70-90 parts of pharmaceutically acceptable auxiliary materials. The composite antibacterial composition and auxiliary materials are acted to prepare a preparation with a corresponding dosage form, so that the composition can be stored, transported and exerted with efficacy and the like.
Specifically, the pharmaceutically acceptable excipients include, but are not limited to, flavoring agents such as sucrose, sorbitol and essence, colorants such as lemon yellow, carmine and sunset yellow, suspending agents such as povidone and dextran, fillers such as lactose, sucrose, mannitol and starch, wetting agents such as water and ethanol, binders such as starch slurry, methyl cellulose, gelatin and hydroxypropylmethyl cellulose, lubricants such as magnesium stearate, talc and polyethylene glycol, PH regulators such as lactic acid, hydrochloric acid and sodium hydroxide, emulsifiers such as gelatin, acacia and magnesium hydroxide, sustained-release coatings such as methacrylic acid value copolymer and ethyl cellulose, fat-soluble bases such as stearic acid, hydrogenated vegetable oil and insect wax, and antioxidants such as vitamin E, tartaric acid and alkyl gallate. Thus, the finally formed formulation may be a solid formulation, such as granules, tablets and powders; liquid preparations such as suspensions, mixtures, emulsions and the like are also possible, but solid preparations and liquid preparations are not limited to the above-mentioned preparations.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
The embodiment provides a composite antibacterial composition, which comprises 3g of florfenicol and 10g of dipsacus asperoides extract, wherein the mass percentage of the saponins VI of dipsacus asperoides in the dipsacus asperoides extract is 6.6%.
The embodiment provides a compound antibacterial preparation, which comprises 3g of florfenicol, 10g of dipsacus asperoides extract and 87 g of auxiliary materials, wherein the auxiliary materials comprise 30g of PEG400 and 57 g of water.
The embodiment provides a preparation method of the composite antibacterial composition, which comprises the following steps:
mixing 1 part of crude drug of radix Dipsaci with 7 parts of 70% ethanol solution, heating and reflux-extracting for 3 times, each time for 2 hr, mixing extractive solutions, drying under reduced pressure to obtain radix Dipsaci extract, wherein per gram of radix Dipsaci extract is 3.3 g of crude drug, and contains radix Dipsaci saponin VI 6.6%.
Mixing the extract of the teasel roots 3g with florfenicol 10g and auxiliary materials 87 g.
Example 2
The embodiment provides a composite antibacterial composition, which comprises 10g of florfenicol and 10g of dipsacus asperoides extract, wherein the mass percentage of the saponins VI of dipsacus asperoides in the dipsacus asperoides extract is 6.8%.
The embodiment provides a compound antibacterial preparation, which comprises 10g of florfenicol, 10g of dipsacus asperoides extract and 90g of auxiliary materials.
The embodiment provides a preparation method of the composite antibacterial composition, which comprises the following steps:
mixing radix Dipsaci crude drug 1 part with 80% ethanol solution 10 parts, heating and reflux extracting for 3 times, each time for 1.5 hr, mixing extractive solutions, and drying under reduced pressure to obtain radix Dipsaci extract containing radix Dipsaci saponin VI 6.8% and 3.4 g crude drug per gram.
Mixing the above 10g of radix Dipsaci extract with 10g of florfenicol and 90g of adjuvants.
Example 3
The embodiment provides a composite antibacterial composition, which comprises 1 g of florfenicol and 5 g of dipsacus asperoides extract, wherein the mass percentage of the dipsacus asperoides VI in the dipsacus asperoides extract is 6.9%.
The embodiment provides a compound antibacterial preparation, which comprises 1 g of florfenicol, 5 g of dipsacus asperoides extract and 70 g of auxiliary materials.
The embodiment provides a preparation method of the composite antibacterial composition, which comprises the following steps:
mixing 1 part of crude drug of radix Dipsaci with 6 parts of 60% ethanol solution, heating and reflux-extracting for 2 times, each time for 3 hr, mixing extractive solutions, drying under reduced pressure to obtain radix Dipsaci extract, wherein per gram of radix Dipsaci extract is 3.3 g of crude drug, and contains radix Dipsaci saponin VI 6.9%.
Mixing the extract of 1 g of dipsacus asperoides with 5 g of florfenicol and 70 g of auxiliary materials.
Example 4
The embodiment provides a composite antibacterial composition, which comprises 20 g of florfenicol and 7 g of dipsacus asperoides extract, wherein the mass percentage of the saponins VI of dipsacus asperoides in the dipsacus asperoides extract is 7.0%.
The embodiment provides a compound antibacterial preparation, which comprises 20 g of florfenicol, 7 g of dipsacus asperoides extract and 80g of auxiliary materials.
The embodiment provides a preparation method of the composite antibacterial composition, which comprises the following steps:
mixing 1 part of crude drug of radix Dipsaci with 10 parts of 65% ethanol solution, heating and reflux-extracting for 3 times, each time for 2 hr, mixing extractive solutions, drying under reduced pressure to obtain radix Dipsaci extract, wherein per gram of radix Dipsaci extract is 3.5 g of crude drug, and contains radix Dipsaci saponin VI 7.0%.
Mixing the above 20 g of radix Dipsaci extract with 7 g of florfenicol and 80g of adjuvants.
Experimental example 1 combination of Dipsacus asperoides extract and florfenicol in vivo pharmacokinetic Effect in broilers
1. Method of producing a composite material
1.1 test grouping
20 healthy chickens were randomly divided into 2 groups of 10 chickens. The test group drenches the medicament according to the mixture ratio in the composite antibacterial composition of the embodiment 1, and specifically comprises the following components: test group medicaments (florfenicol 3g and dipsacus asperoides extract 10g, PEG 40030 g, sterilized water constant volume to 100ml) control group medicaments (florfenicol 3g, PEG 40030 g, sterilized water constant volume to 100ml) were administrated by drenching. The dose of the injection is 2mL/kg body weight, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24h after administration, blood is collected by the inferior pterygoid vein about 0.5mL, EDTA is used for anticoagulation, and is centrifuged for 5min at 4000r/min, and plasma is separated and stored in a refrigerator at the temperature of minus 20 ℃ for standby.
1.2 treatment of the samples
Accurately taking 0.2mL of plasma, adding 10 μ L of chloramphenicol internal standard solution (500 μ g/mL) and 800 μ L of ethyl acetate, vortex mixing for 2min, centrifuging at 4000r/min for 10min, sucking the supernatant into another centrifuge tube, adding 800 μ L of ethyl acetate, repeating the extraction for 1 time, and combining the two extractive solutions. Blowing to dry in 40 deg.C water bath with nitrogen, dissolving the residue in 400 μ L mobile phase, vortex mixing for 2min, centrifuging at 12000r/min for 10min, transferring the supernatant to a sample bottle, and sampling 20 μ L for detection.
1.3 preparation of Standard Curve
Taking 180 mu L of blank plasma, adding 20 mu L of florfenicol series standard solution (500, 200, 100, 50, 25, 5, 1, 0.5 mu g/mL) to prepare 50, 20, 10, 5.0, 2.5, 0.5, 0.1, 0.05 mu g/mL series standard plasma samples, processing the samples according to the method of '1.2', performing linear regression on corresponding florfenicol concentration (c) according to the ratio(s) of the florfenicol peak areas to the chloramphenicol peak areas, and solving a regression equation and a related coefficient to obtain good linear relation of the florfenicol in the range of mass concentration of 0.05-50 mu g/mL, wherein the regression equation is c-0.0.0565 x +0.0218, and the related coefficient R is2The standard curve is shown in fig. 1, which is 0.9997.
1.4 chromatographic conditions
A chromatographic column: agilen HC-C18 (250 mm. times.4.6 mm, 5 μm); mobile phase: acetonitrile-water (27:73, V/V); the flow rate is 1.0 mL/min; the detection wavelength is 223 nm; the column temperature is 40 ℃; the amount of the sample was 20. mu.L.
1.5 analytical methods quality control
The extraction recovery rate and precision of the florfenicol method are examined by using 3 florfenicol concentrations of high, medium and low (0.1 mu g/mL, 2.5 mu g/mL and 20 mu g/mL) of plasma samples, 5 times of the sample are carried out, the recovery rate of the method is respectively measured to be (83.2 +/-1.6)%, (84.1 +/-2.3)% and (83.5 +/-2.2)%, the RSD in the day is respectively measured to be 4.6%, 2.3% and 6.1%, and the RSD in the day is respectively measured to be 4.5%, 2.1% and 6.2%. The lowest detection limit was 0.02 μ g/mL calculated as S/N-3.
2. Results
2.1 method specificity
Under the condition of the chromatogram, the retention time of florfenicol is about 12.8min, and the retention time of chloramphenicol (internal standard) is about 17.2 min. Florfenicol and internal standard are well separated, no interfering impurity is introduced in the sample treatment process, and the endogenous components do not interfere with the separation and determination of the drug (see figure 2, A in figure 2 is blank plasma sample chromatogram, B in figure 2 is plasma sample chromatogram, wherein, 1-florfenicol; 2-internal standard substance)). The method has high specificity, can accurately determine the concentration of the florfenicol in the blood plasma, and has good reproducibility.
2.2 pharmacokinetic parameters
After the test group and the control group of chickens are both administered with the florfenicol according to a single dose (30mg/kg), the blood concentration-time curve of the florfenicol is determined at different time points, and the blood concentration-time curve is shown in figure 3, and the pharmacokinetic parameters are shown in table 1.
TABLE 1
The results showed that AUC (0- ∞) in the test group was 57.907 + -8.12 mg/L.h, significantly increased (P <0.05) compared to 47.729 + -11.601 mg/L.h in the control group, half-life t1/2z was 3.649 + -0.193 h, significantly increased (P <0.05) compared to 2.520 + -0.255 h in the control group, time to peak Tmax was 0.688 + -0.139 h, significantly decreased (P <0.05) compared to 1.250 + -0.141 h in the control group, clearance CLZ was 0.426 + -0.071L/h.kg, significantly decreased (P <0.05) compared to 0.657 + -0.148L/h.kg in the control group, apparent volume of distribution (Vz), peak concentration (Cmax), mean residence time MRT (0- ∞), no significant difference between the test group and the control group, indicating that the combination of Dipsacus extract with florfenicol was significantly increased in comparison to the administration of fenicol alone, as a result of the florfenicol administration, the kinetics occurred, and the change in the absorption rate of florfenicol occurred, the increase of t1/2z and the decrease of CLz indicate that the metabolism of the florfenicol in the body is slowed, and in general, the dipsacus asperoides extract increases the absorption speed of the florfenicol in broiler chickens and slows down the metabolism, so that the AUC is increased finally, and the bioavailability of the florfenicol in the chickens is improved.
Experimental example 2
The mechanism causing the change of pharmacokinetic parameters is researched, and particularly, the influence of the dipsacus asperoides extract on the mRNA expression of CYP3A37, MDR1 and CXR in chicken liver and jejunum is detected.
1.1 test grouping
The 10 healthy broilers were randomly divided into 2 groups of 5 broilers, the test group was administered with Dipsacus asperoides (0.3g/kg, 1 time/d) daily for 7 consecutive days, the blank group was administered with a corresponding volume of physiological saline, after fasting for 12 hours at 8d, two groups of broilers were sacrificed by exsanguination, and liver and jejunum tissues were separated and stored at-80 ℃.
1.2 fluorescent quantitative PCR detection
100mg of tissue was disrupted with a tissue disruptor, and total RNA was extracted by Trizol method according to the instructions. The sample OD260nm/OD280nm ratio was determined to determine RNA concentration and purity, and RNA integrity was checked by agarose gel electrophoresis. The RNA was inverted to cDNA using a reverse transcription kit, and primer sequences for chicken CYP3A37, MDR1, CXR, and housekeeping gene β -actin (synthesized by Shanghai Biotech) were designed using premier5.0 software. Real-time fluorescent quantitative PCR is used for detecting the mRNA transcription level of the gene, and a PCR reaction system is 20 mu L: 2 mu L of cDNA template; upstream and downstream primers (10. mu. mol/L) each 0.4. mu.L; SybrGreen qPCR Master Mix10 μ L; ddH2O7.2. mu.L. The reaction procedure was as follows: pre-denaturation at 95 ℃ for 3 min; denaturation at 95 ℃ for 10s, and annealing at 55-61 ℃ for 15 s; extension at 72 ℃ for 20s for 45 cycles; extension at 60 ℃ for 1 min. As a result, the relative quantitative analysis was used, and the relative expression amount of the gene was calculated by the Δ Ct method. The primer sequences are shown in Table 2.
TABLE 2 fluorescent quantitative PCR primer sequences
2. Results
2.1 Effect of Dipsacus asperoides extract on CYP3A37, MDR1, and CXR mRNA expression in Chicken liver and jejunum
As shown in fig. 4 and fig. 5, after 2 g/chicken continuously orally take the teasel root extract for 7 days, CYP3a37 and CXR mRNA in liver and jejunum are significantly (P <0.05) lower than those in the control group, and MDR1mRNA expression level is also lower than those in the control group, but the difference is not significant (P >0.05), which indicates that the teasel root extract continuously takes for 7 days, has a significant inhibitory effect on CYP3a37 mRNA and MDR1mRNA expression in liver and jejunum of broilers, and also shows a significant down-regulation effect on CXR mRNA expression, suggesting that the teasel root extract may down-regulate CXR mRNA expression, resulting in inhibition of CYP3a7 and P-gp mRNA expression, and further possibly reducing corresponding drug metabolizing enzyme/transporter enzyme activity, and finally causing fast absorption, delayed metabolism and increased bioavailability of florfenicol in intestinal tract, thereby causing changes in florfenicol pharmacokinetic characteristics.
Experimental example 3
The 160 broilers with clinical colibacillosis are randomly selected and divided into three groups of 40 broilers, and A, B, C, D four treatment schemes are adopted, and the four treatment schemes are mixed with feed and administrated at the weight of 0.33g/kg of the broilers for continuous 5 days. Statistical treatment is shown in the following table:
a: example (b): 10g of florfenicol, 10g of dipsacus asperoides extract and 80g of glucose;
b: comparative example 1: 10g of dipsacus asperoides extract and 90g of glucose
C: comparative example 2: 10g of florfenicol, 10g of buffalo horn extract and 80g of glucose;
d: comparative example 3: florfenicol 10g + glucose 90g
Statistics of treatment effects of different drug compatibility groups
| Group of | Animal/head | Cure/head | Death/head | Percent cure rate/%) | Mortality rate/%) |
| |
40 | 38 | 0 | 95％ | 0 |
| |
40 | 22 | 12 | 55％ | 30 |
| Group C | |||||
| 40 | 35 | 0 | 87.5％ | 0 | |
| |
40 | 32 | 0 | 80％ | 0 |
According to the table, the clinical cure rate of the composition provided by the embodiment of the invention on the diarrhea disease of the broiler chicken caused by escherichia coli reaches 95%, and the treatment groups adopting B, C, D preparations are 55%, 87.5% and 80% respectively. The dipsacus asperoides extract has poor treatment effect on the colibacillosis diarrhea, but the curative effect of the florfenicol can be enhanced after the dipsacus asperoides extract is compatible with the florfenicol, and the curative effect is better than that of the florfenicol group which is singly used. Meanwhile, by adopting a buffalo horn extract and florfenicol compound group as a comparison, the effect is also inferior to that of the composition provided by the embodiment of the invention, and the dipsacus asperoides extract can be used as a synergist of the florfenicol and has an obvious synergistic effect.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. An application of a dipsacus asperoides extract in the preparation of a florfenicol synergist.
2. The use of claim 1, wherein the Dipsacus asperoides extract is a mixture of aqueous and alcoholic Dipsacus asperoides extract.
3. Use according to claim 1 or 2, wherein the potentiator is a potentiator that achieves any of the following: (1) the blood concentration of the florfenicol is improved; (2) the bioavailability of the florfenicol is improved; (3) the antibacterial effect of the florfenicol is improved.
4. The composite antibacterial composition is characterized in that the active ingredients comprise 1-20 parts of florfenicol and 5-10 parts of dipsacus asperoides extract in parts by weight.
5. The composite antibacterial composition according to claim 4, wherein the active ingredients comprise 5-20 parts of florfenicol and 5-10 parts of dipsacus asperoides extract;
preferably, the active ingredients comprise 5-20 parts of florfenicol and 5-10 parts of dipsacus asperoides extract in parts by weight;
preferably, the dipsacus asperoides extract is a mixture of aqueous and alcoholic extracts of dipsacus asperoides;
preferably, the mass percentage of the teasel saponin VI in the teasel root extract is not less than 6.6%.
6. A method for preparing the composite antibacterial composition of claim 4, comprising: mixing florfenicol and radix Dipsaci extract at a certain ratio.
7. The method of claim 6, wherein the preparation of the extract of Dipsacus asperoides comprises: mixing radix Dipsaci material with alcohol-water solution at a mass ratio of 1:6-10, heating, reflux extracting at least once, mixing extractive solutions, and concentrating;
preferably, the time for each extraction is 1.5 hours or more;
preferably, the mass of the concentrated extract is one third to two thirds of the mass of the teasel root raw material;
preferably, the alcohol-water solution is an alcohol solution with the mass percent of alcohol of 60-80%;
preferably, the alcohol is a monohydric alcohol, preferably ethanol.
8. A compound antibacterial preparation is characterized in that raw materials comprise, by weight, 1-20 parts of florfenicol, 5-10 parts of dipsacus asperoides extract and 70-90 parts of pharmaceutically acceptable auxiliary materials.
9. The compound antibacterial preparation according to claim 8, wherein the raw materials comprise, by weight, 5-20 parts of florfenicol, 5-10 parts of dipsacus asperoides extract and 70-90 parts of pharmaceutically acceptable excipients.
10. The complex antimicrobial formulation according to claim 8 or 9, wherein the complex antimicrobial formulation is a solid formulation or a liquid formulation;
the solid preparation comprises granules, tablets or powder;
the liquid formulation includes: suspensions, mixtures or emulsions.
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