CN116211929A - Pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture - Google Patents
Pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture Download PDFInfo
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- CN116211929A CN116211929A CN202310259872.9A CN202310259872A CN116211929A CN 116211929 A CN116211929 A CN 116211929A CN 202310259872 A CN202310259872 A CN 202310259872A CN 116211929 A CN116211929 A CN 116211929A
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Abstract
The invention discloses a pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture, and belongs to the technical field of preparation of plants or derivatives thereof. The medicine composition capable of protecting the bacterial septicemia of the megalobrama amblycephala is prepared by combining rheum officinale, phellodendron bark, scutellaria baicalensis, dyers woad leaf, honeysuckle stem and the like according to a certain proportion. The invention has high activity, is directly added into feed for feeding, is absorbed into a blood circulation system through the digestive tract of the megalobrama amblycephala, effectively removes aeromonas hydrophila in the megalobrama amblycephala, antagonizes bacterial infection, repairs capillary vessel tissues, reduces occurrence of diseases, and improves cultivation yield and quality. Wherein, the gallnut, dark plum fruit, coptis root, rhubarb, phellodendron bark and astragalus have the effects of clearing heat and detoxicating, inhibiting bacteria and improving immunity. The Chinese medicinal composition is matched with the folium isatidis and the honeysuckle stem to play a role in heat-clearing, detoxifying, inhibiting bacteria and diminishing inflammation.
Description
Technical Field
The invention relates to the technical field of preparation of plants or derivatives thereof, in particular to a pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture.
Background
Megalobrama amblycephala, also called as marchand, is a freshwater aquaculture fish. Along with the maturation of the culture technology, the culture scale of the megalobrama amblycephala is continuously enlarged, and bacterial septicemia caused by aeromonas hydrophila mainly occurs in the high-incidence period of bacterial diseases in the culture process of the megalobrama amblycephala in 6-9 months. The causes are mainly as follows: (1) The breeding management is not fine, the water quality of the fish pond is aged and deteriorated, the dissolved oxygen is low, the accumulation of harmful substances is excessive, the fish live in a bad water environment all the day, the resistance of the fish body is reduced, and the infection is caused; (2) The feed has incomplete nutrition, unreasonable feeding, excessive fat accumulation in the body, damaged liver and intestinal tract, and reduced resistance, and causes infection.
Chinese patent CN114681538A provides a Chinese medicinal superfine powder for preventing and treating bacterial septicemia of fish and a preparation method thereof, wherein rhubarb, baikal skullcap root, corktree bark, common andrographis herb, dark plum and viola herb are weighed according to the measurement, respectively added into a pulverizer to be pulverized, sieved and blended with each other, and then sieved to obtain the finished product. When in use, the fish bait is mixed with feed according to a certain proportion, the adhesive flour is added to prepare the bait, the bait is continuously fed for a period of time after being dried in the sun, the illness state is gradually controlled, the appetite of the fish shoal is recovered to be normal, the upper jaw, the lower jaw, the oral cavity, the gill cover, eyes and the belly of the fish body are observed to recover to be normal after dissection, the back color of the fish body is changed into the normal color, and the fish shoal grows well after the bait is used, and has no drug residue and no toxic or side effect.
Chinese patent CN109010497a discloses a medicament for treating bacterial sepsis and enteritis of fish and preparation method thereof, which comprises (by weight portions) isatis root 100-150 parts, rhubarb 100-150 parts, coptis root 50-125 parts, capsule of weeping forsythia 75-100 parts, corktree bark 50-100 parts, baikal skullcap root 50-100 parts, licorice root 50-100 parts, andrographis paniculata 25-75 parts, radix scrophulariae 50-75 parts, honeysuckle flower 50-75 parts. The traditional Chinese medicine is prepared by weighing the components according to the measurement, respectively adding the components into a pulverizer for pulverizing, sieving and mixing to obtain a finished product. The preparation method is simple, has low cost, can effectively prevent and treat bacterial septicemia and enteritis of fish, treats both principal and secondary aspect of disease, is safe, has no toxic or side effect and drug resistance, and has no residue in vivo.
In the prior art, the medicine is directly fed for the megalobrama amblycephala to be ingested, however, in actual cultivation, the megalobrama amblycephala is gathered in the middle water area, the directly fed medicine components are easy to settle or flocculate, and the suspension performance in water is poor, so that the effective utilization of the medicine components by the megalobrama amblycephala is less, and the prevention and treatment effect on bacterial septicemia is reduced.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, the present invention aims to provide a pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation.
The medicine composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture comprises medicine components and a compound suspension body, wherein the medicine components comprise the following components in parts by weight: 15-25 parts of gallnut, 15-25 parts of dark plum fruit, 15-25 parts of coptis chinensis, 15-25 parts of rheum officinale, 10-20 parts of amur corktree bark, 10-20 parts of baical skullcap root, 5-10 parts of dyers woad leaf and 5-10 parts of honeysuckle stem.
Preferably, the addition amount of the compound suspension body is 2.4-4.0% of the total mass of the medicinal components.
The invention provides a composite suspension body which is used for improving the suspension performance of a pharmaceutical composition in a water area environment. The compound suspension body consists of a first conjugate body and a second conjugate body with different amino acid chain structures; the first conjugate is obtained by substituting isoprene glycol and chloroacetaldehyde diethyl acetal, then continuing to perform addition reaction with 2-bromopropionyl bromide, esterifying an addition product, performing reduction reaction with L-asparagine to combine the addition product, and polymerizing the final bromo and glycerol monomethacrylate; the second conjugate is obtained by esterification of an addition product, combination of the addition product and L-lysine through reduction reaction, and continuous polymerization of a terminal bromo group and glycerol monomethacrylate.
In the preparation process of the composite suspension, an aldehyde group is formed and selectively connected with the amino end of L-asparagine or L-lysine through a reductive amination reaction, and before in-situ reduction to form stable secondary amine, an imine bond is formed and combined. Multiple initial reaction sites are avoided between reactants, and unwanted byproducts are prevented from being generated. The compound suspending body has good hydrophilicity, can form uniform and stable water dispersion in water after being combined with the drug components, and can form stable suspended colloidal particles by combining amino acid and derivatives thereof with oligomers, thereby improving the suspension efficiency of the drug in water. The composite suspending body does not contain ionic groups with strong interaction, complex aggregates are avoided to be formed among colloidal particles, the average size of suspended colloidal particles is smaller, the soft solid behavior is shown, and the specific amino acid end groups contained in the composite suspending body enhance the effect, so that the deposition or flocculation of the medicinal components can be prevented.
The composite suspending body does not contain phosphate, can avoid eutrophication of the culture water body caused by free phosphorus after use, and reduces the probability of algae and microorganism outbreak, thereby providing a healthy water body environment for the culture of megalobrama amblycephala.
Preferably, the preparation method of the composite suspension body comprises the following steps:
m1, under the anaerobic condition, uniformly mixing potassium hydroxide and isoprene glycol, adding chloroacetaldehyde diethyl acetal, and carrying out substitution reaction; after the substitution reaction is finished, deionized water is added, after the mixture is uniformly mixed, dichloromethane is used for extracting an organic phase, and the organic phase is washed by saturated saline water, dried and distilled under reduced pressure to remove the dichloromethane, so that a substituted product is obtained for later use;
m2, under the anaerobic condition, taking the substitution product, the catalyst and dichloromethane to be uniformly mixed, and adding 2-bromopropionyl bromide for addition reaction; after the addition reaction is finished, filtering and collecting filtrate, washing the filtrate by saturated sodium bicarbonate aqueous solution, drying, and then removing dichloromethane by reduced pressure distillation to obtain an addition product; mixing the addition product with dichloromethane uniformly, adding a catalyst, and carrying out esterification reaction; after the esterification reaction is finished, removing dichloromethane and trifluoroacetic acid by reduced pressure distillation to obtain an esterification product for later use;
m3, taking L-asparagine, a catalyst and a phosphate buffer solution, uniformly mixing, adding the esterification product and carrying out a first reduction reaction; after the first reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a first reduction product; mixing the first reduction product, glycerol monomethacrylate and phosphate buffer solution uniformly, adding a catalyst and carrying out a first polymerization reaction under the anaerobic condition; after the first polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a first conjugate for later use;
m4, mixing L-lysine, a catalyst and a phosphate buffer solution uniformly, adding the esterification product and carrying out a second reduction reaction; after the second reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a second reduction product; mixing the second reduction product, glycerol monomethacrylate and phosphate buffer solution uniformly, adding a catalyst and carrying out a second polymerization reaction under the anaerobic condition; after the second polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a second conjugate for later use;
and M5, uniformly mixing the first conjugate and the second conjugate according to a proportion to obtain the composite suspension.
Specifically, the preparation method of the composite suspension comprises the following steps of, by weight:
under the protection of M1 and nitrogen, uniformly mixing 2.40-3.10 parts of potassium hydroxide and 13.30-17.30 parts of isoprene glycol, adding 3.25-4.25 parts of chloroacetaldehyde diethyl acetal, and carrying out substitution reaction; after the substitution reaction is finished, adding 10-15 parts of deionized water, uniformly mixing, extracting an organic phase by using methylene dichloride, washing the organic phase by using saturated saline water, drying, distilling under reduced pressure to remove the methylene dichloride, and obtaining a substitution product for later use;
under the protection of M2 and nitrogen, 2.90 to 3.75 parts of the substituted product, 2.35 to 3.10 parts of triethylamine and 60 to 80 parts of dichloromethane are taken, evenly mixed, and 2.80 to 3.65 parts of 2-bromopropionyl bromide is added for addition reaction; after the addition reaction is finished, filtering and collecting filtrate, washing the filtrate by saturated sodium bicarbonate aqueous solution, drying, and then removing dichloromethane by reduced pressure distillation to obtain an addition product; taking 1.70-2.20 parts of the addition product and 60-80 parts of dichloromethane, uniformly mixing, adding 70-90 parts of trifluoroacetic acid and carrying out esterification reaction; after the esterification reaction is finished, removing dichloromethane and trifluoroacetic acid by reduced pressure distillation to obtain an esterification product for later use;
m3, taking 2.75-3.55 parts of L-asparagine, 25-30 parts of 2-methylpyridine-N-borane and 100-150 parts of phosphate buffer solution, uniformly mixing, adding 5.85-7.60 parts of esterification product and carrying out first reduction reaction; after the first reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a first reduction product; taking 3.30-4.30 parts of the first reduction product, 9.80-12.75 parts of glycerol monomethacrylate and 75-100 parts of phosphate buffer solution, uniformly mixing, adding 3.55-4.60 parts of tri (2-picolyl) amine and 0.55-0.70 part of copper chloride, and carrying out first polymerization under the protection of nitrogen; after the first polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a first conjugate for later use;
m4, taking 3.05-3.95 parts of L-lysine, 25-30 parts of 2-methylpyridine-N-borane and 100-150 parts of phosphate buffer solution, uniformly mixing, adding 5.85-7.60 parts of the esterification product, and carrying out a second reduction reaction; after the second reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a second reduction product; taking 3.40-4.45 parts of the second reduction product, 9.80-12.75 parts of glycerol monomethacrylate and 75-100 parts of phosphate buffer solution, uniformly mixing, adding 3.55-4.60 parts of tri (2-picolyl) amine and 0.55-0.70 part of copper chloride, and carrying out a second polymerization reaction under the protection of nitrogen; after the second polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a second conjugate for later use;
and M5, uniformly mixing the first conjugate and the second conjugate according to a proportion to obtain the composite suspension.
Preferably, the temperature of the substitution reaction in the step M1 is 110-130 ℃ and the reaction time is 18-36 h.
Preferably, the temperature of the addition reaction in the step M2 is 25-40 ℃ and the reaction time is 6-12 h.
Preferably, the temperature of the esterification reaction in the step M2 is 20-30 ℃ and the reaction time is 2-6 h.
Preferably, the temperature of the first reduction reaction in the step M3 is 35-45 ℃, and the reaction time is 1-4 h.
Preferably, the temperature of the first polymerization reaction in the step M3 is 20-45 ℃ and the reaction time is 4-8 h.
Preferably, the temperature of the second reduction reaction in the step M4 is 30-40 ℃ and the reaction time is 1-3 h.
Preferably, the temperature of the second polymerization reaction in the step M4 is 15-30 ℃, and the reaction time is 3-6 h.
The pH of the phosphate buffer solutions is independently 5.8 to 6.8, preferably pH 6.8.
In the composite suspension, the mass ratio of the first conjugate to the second conjugate is (2.45-3.15): 1, preferably 2.8:1.
the preparation method of the pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation comprises the following steps of:
s1, respectively crushing 15-25 parts of gallnut, 15-25 parts of dark plum, 15-25 parts of coptis chinensis, 15-25 parts of rheum officinale, 10-20 parts of amur corktree bark, 10-20 parts of baical skullcap root, 5-10 parts of dyers woad leaf and 5-10 parts of honeysuckle stem into powder with 150-200 meshes, and then uniformly mixing to obtain medicinal powder for standby;
s2, uniformly mixing the medicinal powder with absolute ethyl alcohol with the same mass, adding a composite suspension body accounting for 2.4-4.0% of the total mass of the medicinal powder, uniformly mixing the medicinal powder and the composite suspension body through ultrasonic treatment, and then removing the absolute ethyl alcohol through reduced pressure distillation to obtain the medicinal composition for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation.
On the basis of conforming to the common knowledge in the field, the above preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the invention.
The invention has the following description and functions of partial raw materials in the formula:
gallnut: the plant Rhus chinensis Mill, rhus ponanii Maxim, or Rhus punjabensis Stew.var.sinica (Diels) Rehd.et Wils, of the family Rhaceae, is mainly formed by the parasite Aphis galla Mela phis chinensis (Bell) Baker. Mainly contains gallnut tannins.
Dark plum: near-ripe fruits of the rosaceae plant Prunus mule Sieb. Et Zucc. Contains 72 volatile oil components, organic acid, amino acid and polysaccharide. The content of citric acid in mume fructus is determined by acid-base titration, and calculated as dry product, the content of organic acid is not less than 15.0% calculated as citric acid. And also contains malic acid, 5-hydroxymethyl-2-furaldehyde, fumaric acid, linoleic acid and other components.
Coptis root: rhizome of Coptis chinensis Franch of Ranunculaceae. Contains berberine, methyl coptisine, palmitoleine, berberine, epiberberine, coptisine, palmatine, jateorhizine, etc.
Rhubarb: dried roots and rhizomes of Rheum palmatum, L.et radix Rheumatopsis tangutica, rheumatopsis tangutica maxim.ex Balf. Or Rheumatopsis pinicola, rheumoj-flina bail. Of Polygonaceae. Mainly contains aloe-emodin, chrysophanol, physcion, rhein, emodin and other components.
Cortex Phellodendri: bark of the rutaceae plant wampee tree Phellodendron chinense schneid. Contains berberine, magnolol, phellodendrine, lactone, sterol, mucilage, flavonoid, alkaloid, volatile oil, sterol, saccharide, etc. Wherein the composition comprises berberine hydrochloride, huang Baigan, stigmasterol, and phellodendron ketone.
Radix Scutellariae Baicalensis: root of Scutellaria baicalensis Georgi Scutellaria baicalensis Georgi belonging to Labiatae. Contains flavonoids, which are effective components of radix Scutellariae, and small amount of sterols and amino acids. The flavonoids mainly comprise baicalin, baicalein, wogonin, baicalein crude ragweed herb, and dihydrooroxylin A.
Folium Isatidis: dried leaves of Isatis tinctoria Isatis Indigotica fort. Contains flavonoid glycoside-shan dao qing glycoside, and also contains indirubin, indigo, wogonin B, indirubin, and furosemide acid.
Caulis Lonicerae: stem and branch of lonicera japonica of lonicera Lonicera japonica thunderb. The stem and vine contains chlorogenic acid and isochlorogenic acid.
The invention has the beneficial effects that:
compared with the prior art, the invention utilizes rhubarb, phellodendron bark, baikal skullcap root, dyers woad leaf, honeysuckle stem and the like to be combined according to a certain proportion, and the medicine combination capable of protecting the megalobrama amblycephala bacterial septicemia is prepared. The invention has high activity, is directly added into feed for feeding, is absorbed into a blood circulation system through the digestive tract of the megalobrama amblycephala, effectively removes aeromonas hydrophila in the megalobrama amblycephala, antagonizes bacterial infection, repairs capillary vessel tissues, reduces occurrence of diseases, and improves cultivation yield and quality. Wherein, the gallnut, dark plum fruit, coptis root, rhubarb, phellodendron bark and astragalus have the effects of clearing heat and detoxicating, inhibiting bacteria and improving immunity. The Chinese medicinal composition is matched with the folium isatidis and the honeysuckle stem to play a role in heat-clearing, detoxifying, inhibiting bacteria and diminishing inflammation.
Compared with the prior art, the invention combines the drug components with the composite suspending body to form uniform and stable water dispersion in the aquaculture water environment, and the conjugate formed by combining the amino acid and the derivative thereof with the oligomer can form stable suspended colloidal particles, thereby improving the suspension efficiency of the drug in water. The composite suspending body does not contain ionic groups with strong interaction, complex aggregates are avoided to be formed among colloidal particles, the average size of suspended colloidal particles is smaller, the soft solid behavior is shown, and the specific amino acid end groups contained in the composite suspending body enhance the effect, so that the deposition or flocculation of the medicinal components can be prevented.
Compared with the prior art, the compound suspension body does not contain phosphate, can avoid eutrophication of the culture water body caused by using free phosphorus, and reduces the outbreak probability of algae and microorganisms, thereby providing a healthy water body environment for the culture of megalobrama amblycephala.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
The comparative example and the examples of the present invention have the following parameters of part of raw materials:
phosphate buffer, ph=6.8, cat: HB8743, qingdao sea Bo Biotechnology Co., ltd.
Example 1
A pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture is prepared by the following method:
s1, respectively crushing 25kg of gallnut, 25kg of dark plum fruit, 15kg of coptis chinensis, 25kg of rheum officinale, 20kg of amur corktree bark, 20kg of baical skullcap root, 5kg of dyers woad leaf and 10kg of honeysuckle stem into 200 meshes of powder, and then uniformly mixing to obtain medicinal powder for later use;
s2, uniformly mixing the medicinal powder with absolute ethyl alcohol with the same mass, adding a composite suspension body with the total mass of 3.2% of the medicinal powder, uniformly mixing the medicinal powder with the composite suspension body through ultrasonic treatment, and then removing the absolute ethyl alcohol through reduced pressure distillation to obtain the medicinal composition for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation.
The preparation method of the composite suspension body comprises the following steps:
under the protection of M1 and nitrogen, uniformly mixing 2.40kg of potassium hydroxide and 13.30kg of isoprene glycol, adding 3.25kg of chloroacetaldehyde diethyl acetal, and carrying out substitution reaction at 120 ℃ for 24 hours; after the substitution reaction is finished, adding 10kg of deionized water, uniformly mixing, extracting an organic phase by using methylene dichloride, washing the organic phase by using saturated saline water, drying, distilling under reduced pressure to remove the methylene dichloride, and obtaining a substituted product for later use;
under the protection of M2 and nitrogen, 2.90kg of the substituted product, 2.35kg of triethylamine and 60kg of dichloromethane are taken and mixed uniformly, 2.80kg of 2-bromopropionyl bromide is added for addition reaction, the temperature of the addition reaction is 35 ℃, and the reaction time is 9h; after the addition reaction is finished, filtering and collecting filtrate, washing the filtrate by saturated sodium bicarbonate aqueous solution, drying, and then removing dichloromethane by reduced pressure distillation to obtain an addition product; taking 1.70kg of the addition product, uniformly mixing with 60kg of dichloromethane, adding 70kg of trifluoroacetic acid, and carrying out esterification reaction at 25 ℃ for 4 hours; after the esterification reaction is finished, removing dichloromethane and trifluoroacetic acid by reduced pressure distillation to obtain an esterification product for later use;
m3, mixing 2.75kg of L-asparagine, 25kg of 2-methylpyridine-N-borane and 100kg of phosphate buffer solution uniformly, adding 5.85kg of the esterification product, and performing a first reduction reaction, wherein the temperature of the first reduction reaction is 40 ℃, and the reaction time is 3 hours; after the first reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a first reduction product; taking 3.30kg of the first reduction product, 9.80kg of glycerol monomethacrylate and 75kg of phosphate buffer solution, uniformly mixing, adding 3.55kg of tri (2-picolyl) amine and 0.55kg of copper chloride, and carrying out a first polymerization reaction under the protection of nitrogen, wherein the temperature of the first polymerization reaction is 35 ℃, and the reaction time is 6 hours; after the first polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a first conjugate for later use;
m4, mixing 3.05kg of L-lysine, 25kg of 2-methylpyridine-N-borane and 100kg of phosphate buffer solution uniformly, adding 5.85kg of the esterification product, and performing a second reduction reaction, wherein the temperature of the second reduction reaction is 30 ℃, and the reaction time is 2 hours; after the second reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a second reduction product; taking 3.40kg of the second reduction product, 9.80kg of glycerol monomethacrylate and 75kg of phosphate buffer solution, uniformly mixing, adding 3.55kg of tri (2-picolyl) amine and 0.55kg of copper chloride, and carrying out a second polymerization reaction under the protection of nitrogen, wherein the temperature of the second polymerization reaction is 25 ℃, and the reaction time is 4 hours; after the second polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a second conjugate for later use;
m5, mixing the first conjugate and the second conjugate according to a mass ratio of 2.8:1, uniformly mixing to obtain the composite suspension body.
Example 2
A pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture is prepared by the following method:
s1, respectively crushing 15kg of gallnut, 15kg of dark plum fruit, 15kg of coptis chinensis, 15kg of rheum officinale, 10kg of amur corktree bark, 10kg of baical skullcap root, 5kg of dyers woad leaf and 5kg of honeysuckle stem into 200 meshes of powder, and then uniformly mixing to obtain medicinal powder for later use;
s2, uniformly mixing the medicinal powder with absolute ethyl alcohol with the same mass, adding a composite suspension body with the total mass of 3.2% of the medicinal powder, uniformly mixing the medicinal powder with the composite suspension body through ultrasonic treatment, and then removing the absolute ethyl alcohol through reduced pressure distillation to obtain the medicinal composition for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation.
The preparation method of the composite suspension body is the same as that of the embodiment 1.
Example 3
A pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture is prepared by the following method:
s1, respectively crushing 25kg of gallnut, 25kg of dark plum fruit, 25kg of coptis chinensis, 25kg of rheum officinale, 20kg of amur corktree bark, 20kg of baical skullcap root, 10kg of dyers woad leaf and 10kg of honeysuckle stem into 200 meshes of powder, and then uniformly mixing to obtain medicinal powder for later use;
s2, uniformly mixing the medicinal powder with absolute ethyl alcohol with the same mass, adding a composite suspension body with the total mass of 3.2% of the medicinal powder, uniformly mixing the medicinal powder with the composite suspension body through ultrasonic treatment, and then removing the absolute ethyl alcohol through reduced pressure distillation to obtain the medicinal composition for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation.
The preparation method of the composite suspension body is the same as that of the embodiment 1.
Example 4
The present example is substantially identical to example 1, except that the preparation method of the composite suspension in this example is as follows:
under the protection of M1 and nitrogen, 3.10kg of potassium hydroxide and 17.30kg of isoprene glycol are uniformly mixed, 4.25kg of chloroacetaldehyde diethyl acetal is added for substitution reaction, the temperature of the substitution reaction is 120 ℃, and the reaction time is 24 hours; after the substitution reaction is finished, adding 15kg of deionized water, uniformly mixing, extracting an organic phase by using methylene dichloride, washing the organic phase by using saturated saline water, drying, distilling under reduced pressure to remove the methylene dichloride, and obtaining a substituted product for later use;
under the protection of M2 and nitrogen, 3.75kg of the substituted product, 3.10kg of triethylamine and 80kg of dichloromethane are taken and mixed uniformly, 3.65kg of 2-bromopropionyl bromide is added for addition reaction, the temperature of the addition reaction is 35 ℃, and the reaction time is 9h; after the addition reaction is finished, filtering and collecting filtrate, washing the filtrate by saturated sodium bicarbonate aqueous solution, drying, and then removing dichloromethane by reduced pressure distillation to obtain an addition product; taking 2.20kg of the addition product, uniformly mixing with 80kg of dichloromethane, adding 90kg of trifluoroacetic acid, and carrying out esterification reaction at 25 ℃ for 4 hours; after the esterification reaction is finished, removing dichloromethane and trifluoroacetic acid by reduced pressure distillation to obtain an esterification product for later use;
m3, mixing 3.55kg of L-asparagine, 30kg of 2-methylpyridine-N-borane and 150kg of phosphate buffer solution uniformly, adding 7.60kg of esterification product and carrying out a first reduction reaction, wherein the temperature of the first reduction reaction is 40 ℃, and the reaction time is 3 hours; after the first reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a first reduction product; taking 4.30kg of the first reduction product, 12.75kg of glycerol monomethacrylate and 100kg of phosphate buffer solution, uniformly mixing, adding 4.60kg of tri (2-picolyl) amine and 0.70kg of copper chloride, and carrying out a first polymerization reaction under the protection of nitrogen, wherein the temperature of the first polymerization reaction is 35 ℃, and the reaction time is 6 hours; after the first polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a first conjugate for later use;
m4, mixing 3.95kg of L-lysine, 30kg of 2-methylpyridine-N-borane and 150kg of phosphate buffer solution uniformly, adding 7.60kg of the esterification product, and performing a second reduction reaction, wherein the temperature of the second reduction reaction is 30 ℃, and the reaction time is 2 hours; after the second reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a second reduction product; taking 4.45kg of the second reduction product, 12.75kg of glycerol monomethacrylate and 100kg of phosphate buffer solution, uniformly mixing, adding 4.60kg of tri (2-picolyl) amine and 0.70kg of copper chloride, and carrying out a second polymerization reaction under the protection of nitrogen, wherein the temperature of the second polymerization reaction is 25 ℃, and the reaction time is 4 hours; after the second polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a second conjugate for later use;
m5, mixing the first conjugate and the second conjugate according to a mass ratio of 2.8:1, uniformly mixing to obtain the composite suspension body.
Example 5
A pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture is prepared by the following method:
s1, respectively crushing 25kg of gallnut, 25kg of dark plum fruit, 15kg of coptis chinensis, 25kg of rheum officinale, 20kg of amur corktree bark, 20kg of baical skullcap root, 5kg of dyers woad leaf and 10kg of honeysuckle stem into 200 meshes of powder, and then uniformly mixing to obtain medicinal powder for later use;
s2, uniformly mixing the medicinal powder with absolute ethyl alcohol with the same mass, adding a suspending body with the total mass of 3.2% of the medicinal powder, uniformly mixing the medicinal powder with the composite suspending body through ultrasonic treatment, and then removing the absolute ethyl alcohol through reduced pressure distillation to obtain the medicinal composition for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation.
The preparation method of the suspension body comprises the following steps:
under the protection of M1 and nitrogen, uniformly mixing 2.40kg of potassium hydroxide and 13.30kg of isoprene glycol, adding 3.25kg of chloroacetaldehyde diethyl acetal, and carrying out substitution reaction at 120 ℃ for 24 hours; after the substitution reaction is finished, adding 10kg of deionized water, uniformly mixing, extracting an organic phase by using methylene dichloride, washing the organic phase by using saturated saline water, drying, distilling under reduced pressure to remove the methylene dichloride, and obtaining a substituted product for later use;
under the protection of M2 and nitrogen, 2.90kg of the substituted product, 2.35kg of triethylamine and 60kg of dichloromethane are taken and mixed uniformly, 2.80kg of 2-bromopropionyl bromide is added for addition reaction, the temperature of the addition reaction is 35 ℃, and the reaction time is 9h; after the addition reaction is finished, filtering and collecting filtrate, washing the filtrate by saturated sodium bicarbonate aqueous solution, drying, and then removing dichloromethane by reduced pressure distillation to obtain an addition product; taking 1.70kg of the addition product, uniformly mixing with 60kg of dichloromethane, adding 70kg of trifluoroacetic acid, and carrying out esterification reaction at 25 ℃ for 4 hours; after the esterification reaction is finished, removing dichloromethane and trifluoroacetic acid by reduced pressure distillation to obtain an esterification product for later use;
m3, mixing 2.75kg of L-asparagine, 25kg of 2-methylpyridine-N-borane and 100kg of phosphate buffer solution uniformly, adding 5.85kg of esterification product, and carrying out reduction reaction at 40 ℃ for 3 hours; after the reduction reaction is finished, collecting sediment through centrifugal treatment, washing the sediment with deionized water, and freeze-drying to obtain a reduction product; taking 3.30kg of the reduction product, 9.80kg of glycerol monomethacrylate and 75kg of phosphate buffer solution, uniformly mixing, adding 3.55kg of tri (2-picolyl) amine and 0.55kg of copper chloride, and carrying out polymerization reaction under the protection of nitrogen, wherein the temperature of the polymerization reaction is 35 ℃, and the reaction time is 6 hours; after the polymerization reaction is finished, collecting the precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain the suspension.
Example 6
A pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture is prepared by the following method:
s1, respectively crushing 25kg of gallnut, 25kg of dark plum fruit, 15kg of coptis chinensis, 25kg of rheum officinale, 20kg of amur corktree bark, 20kg of baical skullcap root, 5kg of dyers woad leaf and 10kg of honeysuckle stem into 200 meshes of powder, and then uniformly mixing to obtain medicinal powder for later use;
s2, uniformly mixing the medicinal powder with absolute ethyl alcohol with the same mass, adding a suspending body with the total mass of 3.2% of the medicinal powder, uniformly mixing the medicinal powder with the composite suspending body through ultrasonic treatment, and then removing the absolute ethyl alcohol through reduced pressure distillation to obtain the medicinal composition for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation.
The preparation method of the suspension body comprises the following steps:
under the protection of M1 and nitrogen, uniformly mixing 2.40kg of potassium hydroxide and 13.30kg of isoprene glycol, adding 3.25kg of chloroacetaldehyde diethyl acetal, and carrying out substitution reaction at 120 ℃ for 24 hours; after the substitution reaction is finished, adding 10kg of deionized water, uniformly mixing, extracting an organic phase by using methylene dichloride, washing the organic phase by using saturated saline water, drying, distilling under reduced pressure to remove the methylene dichloride, and obtaining a substituted product for later use;
under the protection of M2 and nitrogen, 2.90kg of the substituted product, 2.35kg of triethylamine and 60kg of dichloromethane are taken and mixed uniformly, 2.80kg of 2-bromopropionyl bromide is added for addition reaction, the temperature of the addition reaction is 35 ℃, and the reaction time is 9h; after the addition reaction is finished, filtering and collecting filtrate, washing the filtrate by saturated sodium bicarbonate aqueous solution, drying, and then removing dichloromethane by reduced pressure distillation to obtain an addition product; taking 1.70kg of the addition product, uniformly mixing with 60kg of dichloromethane, adding 70kg of trifluoroacetic acid, and carrying out esterification reaction at 25 ℃ for 4 hours; after the esterification reaction is finished, removing dichloromethane and trifluoroacetic acid by reduced pressure distillation to obtain an esterification product for later use;
m3, mixing 3.05kg of L-lysine, 25kg of 2-picoline-N-borane and 100kg of phosphate buffer solution uniformly, adding 5.85kg of the esterification product, and carrying out reduction reaction at the temperature of 30 ℃ for 2 hours; after the reduction reaction is finished, collecting sediment through centrifugal treatment, washing the sediment with deionized water, and freeze-drying to obtain a reduction product; taking 3.40kg of the reduction product, 9.80kg of glycerol monomethacrylate and 75kg of phosphate buffer solution, uniformly mixing, adding 3.55kg of tri (2-picolyl) amine and 0.55kg of copper chloride, and carrying out polymerization reaction under the protection of nitrogen, wherein the temperature of the polymerization reaction is 25 ℃, and the reaction time is 4 hours; after the polymerization reaction is finished, collecting the precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain the suspension.
Comparative example 1
A pharmaceutical composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture is prepared by the following method:
pulverizing Galla chinensis 25kg, mume fructus 25kg, coptidis rhizoma 15kg, radix et rhizoma Rhei 25kg, cortex Phellodendri 20kg, scutellariae radix 20kg, folium Isatidis 5kg, and caulis Lonicerae 10kg into 200 mesh powder respectively, and mixing uniformly to obtain medicinal composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture.
Test example 1
The antibacterial effect of the drug combination for preventing and treating bacterial septicemia in megalobrama amblycephala culture is tested by a bacteriostasis ring test. Pressing the medicinal composition into raw sheets with diameters of 5mm and thicknesses of 2mm, wherein each group of 4 sheets; negative control samples were samples without drug combinations. The test bacteria were Aeromonas hydrophila (ATCC 13040) dipped in a sterile cotton swab at a concentration of 5.0X10 6 CFU/mL test bacterial suspension is uniformly smeared on the surface of a proper culture medium flat plate for 3 times. And (3) each time of smearing, the flat plate rotates for 60 degrees, and finally, the cotton swab is smeared around the edge of the flat plate for one circle. The plate was covered and left to dry at room temperature for 5min. 1 bacteria-contaminated flat plate is pasted and placed in each test, and 4 tablets are pasted and placed on each flat plateTest pieces, 1 negative control piece, and 5 pieces in total. The sample piece is stuck on the surface of the flat plate by using sterile forceps, the negative control sample piece is stuck on the center of the flat plate, the test sample piece is stuck on the periphery, and after the sample piece is stuck, the sample piece is lightly pressed by using the sterile forceps, so that the sample piece is clung to the surface of the flat plate. The distance between the centers of the sample pieces is more than 25mm, and the distance between the centers of the sample pieces and the periphery of the flat plate is more than 15 mm. Plates were covered and incubated at 36℃for 18h for observation, and the test was repeated 3 times. The diameter of the inhibition ring (including the patch) is measured by a vernier caliper and recorded, when the inhibition ring is measured, the inhibition ring which grows uniformly and completely in a sterile mode is selected for carrying out the measurement, and the diameter of the inhibition ring is measured by taking the outer edge of the inhibition ring as a boundary. The antibacterial effect test results are shown in table 1.
Table 1:
negative control specimens were free of inhibition zones. According to the definition in the standard, the diameter of the antibacterial ring of the test sample is more than 7mm, and the test sample is judged to have antibacterial effect; and if the diameter of the inhibition ring is less than or equal to 7mm, judging that the inhibition ring has no inhibition effect. As can be seen from the test results in Table 1, the pharmaceutical combinations of different dosages of the present invention have antibacterial effect on Aeromonas hydrophila.
Test example 2
And carrying out toxicity counteracting tests on the drug combination for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation. The experimental group respectively adds a drug combination for preventing and treating bacterial septicemia in megalobrama amblycephala culture according to 5 weight percent of basic feed, takes florfenicol as a reference group of the existing drug, and adopts aeromonas hydrophila (ATCC 13040) to attack the toxin; feeding basic feed in blank control, and counteracting toxic substances by using sterile normal saline; the negative control is fed with basic feed, and aeromonas hydrophila is used for counteracting toxin. And (5) temporarily raising the megalobrama amblycephala for 1 week before the test formally begins, and feeding basic feed during the temporary raising period. Hunger of megalobrama amblycephala for 24 hr before test, and selecting 50 (50.23+ -2.53) g health and uniform specificationFor the breeding test, 3 replicates of each group were placed in 21 identical size cages (1 m) each with 50 tails. The trial period was 2 weeks, with feeding on week 1 with apparent satiety twice daily (8:00 and 16:00). Periodically detecting water quality, wherein the water temperature is between 24 and 30 ℃, and ammonia nitrogen<0.5mg/L, pH of 7.5-8.5, dissolved oxygen>5mg/L, 1 time of water change every 3 days, and the water change amount accounts for about 1/3 of the water capacity of the net cage. Starting the aeromonas hydrophila toxicity test at week 2, diluting aeromonas hydrophila with sterile physiological saline to 1×10 4 CFU/ml. The negative control and experimental groups were injected into the chest using a disposable sterile syringe with 200ul of bacteria. The blank control group is injected with sterile physiological saline and is normally fed during the toxin attacking period. The number of deaths per group was recorded for 7 days and survival was counted. The results of the toxicity test are shown in Table 2.
Table 2:
| name of the name | Survival (%) |
| Example 1 | 88.7 |
| Example 5 | 80.0 |
| Example 6 | 78.7 |
| Comparative example 1 | 71.3 |
| Florfenicol | 86.0 |
| Blank control | 100.00 |
| Negative control | 44.7 |
The toxicity counteracting experiment shows that the medicine composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture can have good protection rate on megalobrama amblycephala infected with aeromonas hydrophila, wherein the effect of the embodiment 1 is similar to that of florfenicol.
Test example 3
The suspension performance of the drug combination in water for preventing and treating bacterial septicemia in megalobrama amblycephala culture is tested. Preparing a to-be-tested sample into a suspension with proper concentration, weighing 5g of a pharmaceutical composition sample, placing the pharmaceutical composition sample into a 200mL beaker containing 50mL of 30 ℃ water, shaking the beaker by hand for circular motion, carrying out 120 times per minute for 2 minutes, placing the suspension in a water bath with the same temperature for 13 minutes, washing all the suspension into a 250mL measuring cylinder with the water with the temperature of 30 ℃ and diluting the suspension to a scale, covering a plug, taking the bottom of the measuring cylinder as an axis, and reversing the measuring cylinder from top to bottom for 30 times within 1 minute. Opening the plug, vertically placing into vibration-free constant temperature water bath, preventing direct sunlight, and standing for 30min. The 9/10 (i.e., 225 mL) suspension of the contents was removed with the pipette within 10 seconds without shaking or lifting the sediment in the cylinder, ensuring that the tip of the pipette was always a few millimeters below the liquid surface. The combined mass of the sample and the drug remaining in 25mL of suspension at the bottom of the measurement. The suspension rate is calculated according to the following formula:
wherein:
m 1 the mass of the drug combination in grams (g) in the sample taken to prepare the suspension;
m 2 to leave 25mL of the suspension in the bottom of the cylinderThe combined mass is given in grams (g).
The results of the suspension performance test of the drug combination in water for preventing and treating bacterial septicemia in megalobrama amblycephala culture are shown in Table 3.
Table 3:
| name of the name | Suspension percentage (%) |
| Example 1 | 87.1 |
| Example 5 | 81.5 |
| Example 6 | 74.9 |
| Comparative example 1 | 39.4 |
Example 1 exhibited the best suspension performance compared to comparative example 1 without the addition of the composite suspension body. This result may be due to the formation of an imine bond and the subsequent bonding during the preparation of the complex suspension by the formation of an aldehyde group and the selective attachment of the amino terminus of L-asparagine or L-lysine by a reductive amination reaction, prior to the in situ reduction to form a stable secondary amine. Multiple initial reaction sites are avoided between reactants, and unwanted byproducts are prevented from being generated. The compound suspending body has good hydrophilicity, can form uniform and stable water dispersion in water after being combined with the drug components, and can form stable suspended colloidal particles by combining amino acid and derivatives thereof with oligomers, thereby improving the suspension efficiency of the drug in water. The composite suspending body does not contain ionic groups with strong interaction, complex aggregates are avoided to be formed among colloidal particles, the average size of suspended colloidal particles is smaller, the soft solid behavior is shown, and the specific amino acid end groups contained in the composite suspending body enhance the effect, so that the deposition or flocculation of the medicinal components can be prevented.
Claims (10)
1. The medicine composition for preventing and treating bacterial septicemia in megalobrama amblycephala culture comprises medicine components and a compound suspension body, and is characterized in that the medicine components comprise the following components in parts by weight: 15-25 parts of gallnut, 15-25 parts of dark plum fruit, 15-25 parts of coptis chinensis, 15-25 parts of rheum officinale, 10-20 parts of amur corktree bark, 10-20 parts of baical skullcap root, 5-10 parts of dyers woad leaf and 5-10 parts of honeysuckle stem; the compound suspension body consists of a first conjugate body and a second conjugate body with different amino acid chain structures, wherein the first conjugate body is subjected to addition reaction with 2-bromopropionyl bromide after being substituted by isoprene glycol and chloroacetaldehyde diethyl acetal, then an addition product is subjected to reduction reaction with L-asparagine after being esterified and combined, the final end bromo group is polymerized with glycerol monomethacrylate to obtain the first conjugate body, and the second conjugate body is subjected to reduction reaction with L-lysine after being esterified and combined with the L-lysine, and the final end bromo group is subjected to polymerization reaction with glycerol monomethacrylate to obtain the compound suspension body.
2. The pharmaceutical combination for preventing and treating bacterial sepsis in megalobrama amblycephala culture according to claim 1, characterized in that: the addition amount of the compound suspension body is 2.4-4.0% of the total mass of the medicine components.
3. The pharmaceutical composition for preventing and treating bacterial sepsis in megalobrama amblycephala culture according to claim 1 or 2, wherein the preparation method of the compound suspension is as follows in parts by weight:
under the protection of M1 and nitrogen, uniformly mixing 2.40-3.10 parts of potassium hydroxide and 13.30-17.30 parts of isoprene glycol, adding 3.25-4.25 parts of chloroacetaldehyde diethyl acetal, and carrying out substitution reaction; after the substitution reaction is finished, adding 10-15 parts of deionized water, uniformly mixing, extracting an organic phase by using methylene dichloride, washing the organic phase by using saturated saline water, drying, distilling under reduced pressure to remove the methylene dichloride, and obtaining a substitution product for later use;
under the protection of M2 and nitrogen, 2.90 to 3.75 parts of the substituted product, 2.35 to 3.10 parts of triethylamine and 60 to 80 parts of dichloromethane are taken, evenly mixed, and 2.80 to 3.65 parts of 2-bromopropionyl bromide is added for addition reaction; after the addition reaction is finished, filtering and collecting filtrate, washing the filtrate by saturated sodium bicarbonate aqueous solution, drying, and then removing dichloromethane by reduced pressure distillation to obtain an addition product; taking 1.70-2.20 parts of the addition product and 60-80 parts of dichloromethane, uniformly mixing, adding 70-90 parts of trifluoroacetic acid and carrying out esterification reaction; after the esterification reaction is finished, removing dichloromethane and trifluoroacetic acid by reduced pressure distillation to obtain an esterification product for later use;
m3, taking 2.75-3.55 parts of L-asparagine, 25-30 parts of 2-methylpyridine-N-borane and 100-150 parts of phosphate buffer solution, uniformly mixing, adding 5.85-7.60 parts of esterification product and carrying out first reduction reaction; after the first reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a first reduction product; taking 3.30-4.30 parts of the first reduction product, 9.80-12.75 parts of glycerol monomethacrylate and 75-100 parts of phosphate buffer solution, uniformly mixing, adding 3.55-4.60 parts of tri (2-picolyl) amine and 0.55-0.70 part of copper chloride, and carrying out first polymerization under the protection of nitrogen; after the first polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a first conjugate for later use;
m4, taking 3.05-3.95 parts of L-lysine, 25-30 parts of 2-methylpyridine-N-borane and 100-150 parts of phosphate buffer solution, uniformly mixing, adding 5.85-7.60 parts of the esterification product, and carrying out a second reduction reaction; after the second reduction reaction is finished, collecting a precipitate through centrifugal treatment, and washing the precipitate with deionized water and freeze-drying to obtain a second reduction product; taking 3.40-4.45 parts of the second reduction product, 9.80-12.75 parts of glycerol monomethacrylate and 75-100 parts of phosphate buffer solution, uniformly mixing, adding 3.55-4.60 parts of tri (2-picolyl) amine and 0.55-0.70 part of copper chloride, and carrying out a second polymerization reaction under the protection of nitrogen; after the second polymerization reaction is finished, collecting a precipitate through centrifugal treatment, washing the precipitate with deionized water, and freeze-drying to obtain a second conjugate for later use;
and M5, uniformly mixing the first conjugate and the second conjugate according to a proportion to obtain the composite suspension.
4. A pharmaceutical combination for the prevention and treatment of bacterial sepsis in megalobrama amblycephala culture according to claim 3, characterized in that: the temperature of the substitution reaction in the step M1 is 110-130 ℃, and the reaction time is 18-36 h.
5. A pharmaceutical combination for the prevention and treatment of bacterial sepsis in megalobrama amblycephala culture according to claim 3, characterized in that: the temperature of the addition reaction in the step M2 is 25-40 ℃ and the reaction time is 6-12 h; the temperature of the esterification reaction is 20-30 ℃ and the reaction time is 2-6 h.
6. A pharmaceutical combination for the prevention and treatment of bacterial sepsis in megalobrama amblycephala culture according to claim 3, characterized in that: the temperature of the first reduction reaction in the step M3 is 35-45 ℃ and the reaction time is 1-4 h; the temperature of the first polymerization reaction is 20-45 ℃ and the reaction time is 4-8 h.
7. A pharmaceutical combination for the prevention and treatment of bacterial sepsis in megalobrama amblycephala culture according to claim 3, characterized in that: the temperature of the second reduction reaction in the step M4 is 30-40 ℃ and the reaction time is 1-3 h; the temperature of the second polymerization reaction is 15-30 ℃ and the reaction time is 3-6 h.
8. A pharmaceutical combination for the prevention and treatment of bacterial sepsis in megalobrama amblycephala culture according to claim 3, characterized in that: the pH of the phosphate buffer solution is respectively and independently 5.8-6.8.
9. A pharmaceutical combination for the prevention and treatment of bacterial sepsis in megalobrama amblycephala culture according to claim 3, characterized in that: the mass ratio of the first conjugate to the second conjugate is (2.45-3.15): 1.
10. a method for preparing the pharmaceutical composition for preventing and treating bacterial sepsis in megalobrama amblycephala culture according to claim 1, comprising the following steps in parts by weight:
s1, respectively crushing 15-25 parts of gallnut, 15-25 parts of dark plum, 15-25 parts of coptis chinensis, 15-25 parts of rheum officinale, 10-20 parts of amur corktree bark, 10-20 parts of baical skullcap root, 5-10 parts of dyers woad leaf and 5-10 parts of honeysuckle stem into powder with 150-200 meshes, and then uniformly mixing to obtain medicinal powder for standby;
s2, uniformly mixing the medicinal powder with absolute ethyl alcohol with the same mass, adding a composite suspension body accounting for 2.4-4.0% of the total mass of the medicinal powder, uniformly mixing the medicinal powder and the composite suspension body through ultrasonic treatment, and then removing the absolute ethyl alcohol through reduced pressure distillation to obtain the medicinal composition for preventing and treating bacterial septicemia in megalobrama amblycephala cultivation.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1399541A (en) * | 1999-11-23 | 2003-02-26 | 弗拉梅技术公司 | Colloidal suspension of submicronic particles as vectors for active principles and method for preparing same |
| CN104352617A (en) * | 2014-10-11 | 2015-02-18 | 中国科学院海洋研究所 | Sanhuang supper micropowder as well as preparing method and application thereof |
| CN110664937A (en) * | 2019-11-25 | 2020-01-10 | 湖南利农五倍子产业发展有限公司 | Compound aquatic bactericide containing gallic acid and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1399541A (en) * | 1999-11-23 | 2003-02-26 | 弗拉梅技术公司 | Colloidal suspension of submicronic particles as vectors for active principles and method for preparing same |
| CN104352617A (en) * | 2014-10-11 | 2015-02-18 | 中国科学院海洋研究所 | Sanhuang supper micropowder as well as preparing method and application thereof |
| CN110664937A (en) * | 2019-11-25 | 2020-01-10 | 湖南利农五倍子产业发展有限公司 | Compound aquatic bactericide containing gallic acid and preparation method thereof |
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