CN104511016A - Pharmaceutical composition for controlling diseases of aquatic animals and applications thereof - Google Patents
Pharmaceutical composition for controlling diseases of aquatic animals and applications thereof Download PDFInfo
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Farming Of Fish And Shellfish (AREA)
Abstract
The invention discloses a pharmaceutical composition for controlling the diseases of aquatic animals. The pharmaceutical composition is composed of two components: quinolone antibiotics and berberine. Compared to the prior art, the provided pharmaceutical composition has the advantages of definite curative effect on viral and bacterial diseases of aquatic animals (especially grass carp), user-friendliness, moderate cost, easiness for massive promotion and application, difficulty in generating drug resistance and drug tolerance, safety for aquatic animals, low toxicity, and low residues.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition preventing and treating aquatic animal disease, this pharmaceutical composition can be used for viral, the bacterial disease of preventing and treating the hemorrhagic disease that caused by reovirus of Ctenopharyngodon idellus and other aquatic animals (fish, shrimp, Eriocheir sinensis, the frog, Trionyx sinensis Wiegmann).
Background technology
The viral disease of aquatic animal (fish, shrimp, Eriocheir sinensis, the frog, Trionyx sinensis Wiegmann etc.) (viral hemorrhagic of the Ctenopharyngodon idellus especially caused by reovirus is sick) comprises research of hemorrhage of grass carp, fulminant hemorrhagic disease, crucian carp Simplex Virus, taura syndrome virus is sick and tarda is sick and gill rot, enteritis, ulcer, the rotten tail of rotten fin etc. are sick etc.
The symptom of research of hemorrhage of grass carp: this sick main infection harm Ctenopharyngodon idellus young fish of two years, fingerlings of two years, in addition one age fish and seed and two ages above adult fish also can infect, outward appearance symptom main manifestations has three kinds: 1. red fin red gill cover type: see each fin ray of fish and base portion hyperemia rubescent, the gill cover and lower jaw hyperemia, rouge swelling, anemia, there is ascites in middle and late stage abdominal cavity, and hepatopancrease turns white or is red, alternate in vain colored liver shape.2. red muscularity: the hyperemia of fish body surface is rubescent, or hemorrhage in speckle shape, and subdermal muscle hyperemia is rubescent, and Di inflammation pathological changes, hepatopancrease turns white.3. enteritis gill rot type: except the gill cover, jaw portion, fin ray and base portion body surface in various degree hyperemia, bowel symptoms hyperemia, hindgut inflammation or ulcer, there is ascites in abdominal cavity, internal organs anemia, gill rot.
Research of hemorrhage of grass carp epidemiology situation, their early stage symptom is not obvious, in, later stage fish body constitution is weak, secondary infection antibacterial presents body surface and each organ hemorrhage of internal organs, inflammation, anemia, gill rot, intestinal is scorching, ulcer, the symptoms such as hepatopancrease is impaired, this sick mortality rate is up to 60-90%, very harmful, to antibiotics, antibiotic is insensitive, the main way prevention adopting injecting immune vaccine and soaking vaccine in the past, but immersion immunity vaccine climate, water temperature, water quality impact, effect is unstable, in addition complicated operation, cannot spread, injecting immune vaccine inconvenient operation, waste time and energy, in addition large to fish bulk damage, therefore except cage culture, be difficult to spread in actual production.
Fulminant hemorrhagic disease, cause of disease is Aeromonas hydrophila (Aeromonas hydrophila, AH), this cause of disease is conditionality pathogenic bacterium, knownly at present cause Cyprinus carpio, crucian carp, bream, triangular bream, flower, silver carp, salmon, Squaliobarbus ourriculus, Acipenser Sinensis, Channel-catfish, Nian, tilapia, Carnis Pseudosciaenae, turbot, Chinese yellow eel, the seas such as eel, fresh-water fishes and the frog, the aquatic animals such as Trionyx sinensis Wiegmann are caused a disease, because its infection rate is high, dead fast, common name " fulminant hemorrhagic disease " or " bacterial septicemia ", a kind of typical people, poultry, fish is ill cause of disease altogether, cardinal symptom: fish body surface, the gill cover, lower jaw, fin bar, abdominal part is congested rubescent in various degree, severe patient muscle is speckle or mottled hemorrhage, gill filament anemia, the each organ anemia of internal organs, there is hydrops in severe patient abdominal cavity, some individuals has gill rot, intestinal is scorching, beancurd sheet, liver and gallbladder syndrome, the rotten tail symptom of rotten fin.
Crucian carp Simplex Virus (Cyprinid Herpesvirus), dead fish symptom: gill filament swelling, significantly hemorrhage, the gill cover, lower jaw part, abdominal part be speckle shape or put hemorrhage, fin ray is rubescent, fin base portion is rubescent, abdominal cavity ascites, hepatopancrease turn white or in " flower liver shape " red and white, rear enteremia or have dope, anus is congested red and swollen, exophthalmos, tail fin fringing, serious tail fin moth fin, liver is khaki or " bean curd slag specimen " pathological changes, and indivedual fish dorsal is in " furuncle sample " pathological changes.
Taura syndrome virus (TSV) disease and Taura syndrome virus.TSV reveal any symptoms are: shrimp tail, palpus, body surface are rubescent, some individual outward appearance symptom is not obvious, body colour is grey, red, shoal of shrimps often occurs touring around phenomenon, there is blue spot in indivedual shrimp tail fan, liver pancreas enlargement or in pale red, muscle is muddy, later stage symptom: red palpus, red tail, soft shell etc.
Tarda (Edwardsiella lctalarus) symptom: Trionyx sinensis Wiegmann abdominal part is that speckle sheet is hemorrhage, neck enlargement, carapace ulcer, dissect and find liver enlargement, indivedual focus is festered, and has ascites, frog lower limb is petechial hemorrhage, and exophthalmos has petechial hemorrhage with it, visceral congestion, hepatic necrosis, tilapia exophthalmos, the gill, jaw, abdominal part are hemorrhage rubescent, liver is flower liver, khaki, turning white has necrotic lesion, and health has furuncle sample focus, and some individuals is the symptoms such as gill rot, enteritis, beancurd sheet.
The viral disease of aquatic animal, existing Therapeutic Method is except employing injection or immersion immunity vaccine, always without effective medical treatment, in addition, the fish caused by bacteriological infection, shrimp, Eriocheir sinensis, the frog, the gill rot of the aquatic animals such as Trionyx sinensis Wiegmann, intestinal is scorching, red skin (beancurd sheet), ulcer, rotten fin, rotten tail, liver and gallbladder syndrome, the disease such as hemorrhage (septicemia) adopts traditional sulphonamides, macrolide antibiotics (florfenicol, first vitriol mycin), Tetracyclines (oxytetracycline, doxycycline) etc. produced serious Drug resistance because of long-term medication, drug resistance, dosage is large, weak effect, the open defects such as high expensive.
Summary of the invention
An object of the present invention is just to provide a kind of pharmaceutical composition preventing and treating aquatic animal disease, and this pharmaceutical composition can be used for viral, the bacterial disease of preventing and treating the hemorrhagic disease that caused by reovirus of Ctenopharyngodon idellus and other aquatic animals (fish, shrimp, Eriocheir sinensis, the frog, Trionyx sinensis Wiegmann).
Technical scheme is: a kind of pharmaceutical composition preventing and treating aquatic animal disease, and this pharmaceutical composition preventing and treating aquatic animal disease is made up of following two kinds of compositions: quinolone antibiotic and berberine.
As preferably, described quinolone antibiotic: berberine weight ratio is 10-40:3.3-9.
As preferably, described quinolone antibiotic is norfloxacin, enrofloxacin, ofloxacin or ciprofloxacin.
As preferably, described norfloxacin is Norfloxacin Lactate, norfloxacin nicotinate or norfloxacin hydrochloride; Described ciprofloxacin is ciprofloxacin, ciprofloxacin lactate or nicotinic acid ciprofloxacin.
As preferably, described berberine is berberine hydrochloride or berberine sulfate.
Two of object of the present invention is the purposes providing a kind of pharmaceutical composition.
Technical scheme is: a kind of purposes of aforementioned pharmaceutical compositions: this pharmaceutical composition for preventing and treating research of hemorrhage of grass carp, fulminant hemorrhagic disease, crucian carp Simplex Virus, Fructus Persicae draw syndrome virus or tarda is sick
Beneficial effect:
1) pharmaceutical composition in vitro tests of the present invention has remarkable preventive effect to reovirus, irido virus, infectious hematopoietic necrosis's poison, rhabdovirus, herpesvirus, white spot syndrome virus, taura syndrome virus, and in vitro tests confirms the phagocytic activity that can strengthen leukocyte and liver reticuloendothelial system; This alkaloid has a broad antifungal spectrum, all has inhibitory action to multiple gram negative bacteria, positive bacteria simultaneously.All have stronger inhibitory action to Cytophaga Columnaris, Aeromonas hydrophila, pseudomonas, Aeromonas, tarda, slime bacteria, vibrio, streptococcus, and norfloxacin (ciprofloxacin, enrofloxacin) is mainly used in preventing and treating the bacterial disease caused by Aeromonas, pseudomonas, tarda, slime bacteria.
2) after medication; the research of hemorrhage of grass carp protective rate caused by reovirus; two age large size fingerling be greater than 80%; yearlings or two ages above adult fish protective rate be greater than 90%; 90% is greater than for gill rot, enteritis, red skin (beancurd sheet), ulcer, rotten fin, rotten tail, hemorrhage (septicemia) sick cure rate, with the medicine of liver-gallbladder disease is composite, 86% is greater than to liver and gallbladder syndrome effective percentage.
3) the control effective percentage of pharmaceutical composition of the present invention to the hemorrhagic disease that GCRV causes reaches more than 80%, as long as Ctenopharyngodon idellus can have enough pharmaceutical chemistry, just there is obvious curative effects, have easy and simple to handle, determined curative effect, with low cost, be easy to the feature promoted the use of, be the up to now unique effective medicine of this disease of prevention and control Ctenopharyngodon idellus.In addition, this compound medicine also can effectively prevention and control shrimp, Eriocheir sinensis, fish by virus or bacteriological infection cause gill rot, enteritis, hemorrhage (septicemia), red skin (beancurd sheet), ulcer, rotten fin, rotten tail, liver and gallbladder syndrome.Have compared with other drug effective, easy to use, not easily develop immunity to drugs, drug resistance, to medication animal subject safety, low toxicity, have the significant advantage of obvious control effect when employing this product that other drug is invalid or effect is undesirable.
4) pharmaceutical composition of the present invention prevents and treats aquatic animal viral (particularly Ctenopharyngodon idellus) bacterial disease determined curative effect, easy to use, moderate cost, is easy to spread and uses, not easily develop immunity to drugs, drug resistance, to dispenser object security, low toxicity, low-residual.
Detailed description of the invention
Experiment 1
1), the preparation of pharmaceutical composition A: get norfloxacin 10-20 weight portion, berberine 3.3-4.5 weight portion mixes.
2), research of hemorrhage of grass carp is treated
Choose net cage 5 × 5 × 2 meters of specifications, every net cage put 500 gram/fish two age Grass carp 3000 kilograms, totally 6000 tails, if No. 1, experimental box, No. 2, contrast No. 3, case, No. 4, No. 5, blank case, No. 6, experimental situation condition is as water temperature, pH value, the physical and chemical indexs such as weather are basically identical, and perfect compound feed used selects logical prestige Ctenopharyngodon idellus to be bred as material, and management level are identical, experimental session on March 1st, 2012 to JIUYUE 30 days, May 16 No. 1, No. 2, No. 3, No. 4, No. 5, No. 6 casees start morbidity in succession, be because of research of hemorrhage of grass carp on inspection, cause of disease warp is reovirus (gross Corp nemorrhoge virus with determining isolation identification, GCHV), to May 19 respectively group case infect and dead movement pattern of fish condition in table 1, after making a definite diagnosis, the drug regimen A configured is used for No. 1, proof box, No. 2 (calculating dose by every 1 kilogram of fish body weight 13.3-24.5mg), is used in conjunction 5 days, and contrast case is got florfenicol (content >=98%) and calculated dose by every 1 kilogram of fish body weight 15mg, mixes to raise (bait) material and throw something and feed No. 3, No. 4 casees 5 days, No. 5, No. 6 casees are made blank group and are not offerd medicine, and on May 20 to 24 offerd medicine, the effect observation post administration phase 25 to 30 May, and the dead movement pattern of fish condition of each group case is in table 1.
The dead fish of each case of table 1 (tail) situation is added up
Result as can be seen from experiment 1: drug regimen A research of hemorrhage of grass carp early stage or significantly fall ill mid-term (mortality rate is up to 20%) time protective rate of throwing something and feeding reach more than 70%, and florfenicol antimicrobial drug of throwing something and feeding organizes mortality rate all up to more than 90% with not offeing medicine.Prove that this drug regimen A has remarkable preventive effect to the research of hemorrhage of grass carp caused by reovirus.
Experiment 2
1), the configuration of pharmaceutical composition B: get enrofloxacin 15-20 weight portion, berberine 3.3-4.5 weight portion mixes.
2), fulminant hemorrhagic disease is treated
Cyprinus carpio 10000 tail chosen by every net cage, specification 500 grams/fish, sets up 6, net cage separately, cage size 4 × 7 × 2 meters, No. 1, No. 2 casees are experimental group, No. 3, No. 4 casees are matched group, and No. 5, No. 6 casees are blank group, and duration of test on March 6th, 2012 was to June 30, duration of test environmental condition is respectively organized substantially identical, record temperature, water temperature, dissolved oxygen, pH value change every day, within 3 days, measure nitrite nitrogen, an ammonia nitrogen index, feeds utilized is logical prestige Cyprinus carpio incubation material.
Each case phase secondary disease, from sick fish lesions position, divided by bacteriology and roughly the same surely confirmed as fulminant hemorrhagic disease May 10.
The pharmaceutical composition B prepared got by May 12 No. 1, No. 2 casees, 18.3-24.5mg is pressed by every 1 kilogram of fish body weight daily dose, mix bait (raising) material lighter No. 1 case of the state of an illness of throwing something and feeding and be used in conjunction 3 days, No. 2 case state of an illness are heavier is used in conjunction 5 days, No. 3, matched group, No. 4 casees are used in conjunction 5 days by every 1 kilogram of fish body weight daily dose by doxycycline hydrochloride 20mg, the not medication of blank group, the dead movement pattern of fish condition of each networking case in 10 to 19 May is in table 2.
The dead fish of each net cage of table 2 (tail) situation is added up
Show through above experiment: pharmaceutical composition B is used in conjunction 3 days to the fulminant hemorrhagic disease treatment that Aeromonas hydrophila causes, serious symptom is used in conjunction 5 days significant curative effect, and doxycycline hydrochloride has obvious reduction than without antibiotic group mortality rate, after drug withdrawal, mortality rate continues to rise, and shows aeromonas hydrophila disease curative effect not good enough.
Experiment 3
1), the preparation of pharmaceutical composition C: get enrofloxacin 15-20 weight portion, berberine 3.3-4.5 weight portion mixes.
2), crucian carp Simplex Virus is treated
Experiment chooses 2 mu of areas, 6 mouthfuls, the depth of water 1.8 meters of ponds, and experiment pool is made in wherein No. 1, No. 3 ponds, No. 2, No. 4 ponds compare group, and No. 5, No. 6 ponds do blank group, put Carassius auratus 3000 tail in a suitable place to breed for every mu, specification 50 grams/fish, Ctenopharyngodon idellus 100 tail, specification 250 grams/fish, silver carp 100 tail, specification 250 grams/fish, Aristichthys nobilis 20 tail, specification 500 grams/fish, the environmental conditions such as water source, each pond, weather, water temperature are consistent, and management level are identical, select logical prestige crucian carp feed.Experimental session on April 1st, 2012 was to June 30.
April 20 each fishpond phase secondary disease, from sick fish lesions position isolation identification, making a definite diagnosis is crucian carp Simplex Virus (Cyprinid Herpesvirus).
April 21 No. 1, No. 3 experiment pool get the pharmaceutical composition C prepared, mix bait (raising) by every 1 kilogram of fish body weight daily dose 18.5-24.5mg to throw something and feed, No. 1 pond disease is gentlier used in conjunction 3 days, No. 3 ponds are heavier is used in conjunction 5 days, and No. 2 ponds, No. 4 ponds compare, by 1 kilogram of fish body weight daily dose enrofloxacin 40mg, No. 2 ponds are used in conjunction 5 days, No. 4 ponds are used in conjunction 7 days, and blank not medication is done in No. 5, No. 6 ponds, and the dead movement pattern of fish condition in each pond in 20 to 29 April is in table 3.
The dead fish in each pond of table 3 (tail) is added up
As can be seen from above experiment, herpesvirus is insensitive to antimicrobial drugs such as enrofloxacins, during dispensing, mortality rate declines to some extent than the blank group of not offeing medicine, may be that after antimicrobial drug infects herpesvirus to sick fish, each organ secondary infection antibacterial has certain inhibitory action, but after drug withdrawal, mortality rate is on the rise, and final mortality rate is close with group of not offeing medicine, and drug regimen C has significant curative effect to this disease.
Experiment 4
1), the preparation of pharmaceutical composition D: get enrofloxacin 20-40 weight portion, berberine 4.5-9 weight portion mixes.
2) taura syndrome virus, is treated sick
Choose 1 mu of area, 6 mouthfuls, the depth of water 0.8 meter of pond, experiment pool is made in wherein No. 1, No. 3 ponds, No. 2, No. 4 ponds compare pond, do blank group for No. 5, No. 6, shrimp 1500 tail is put in every mu of pond, and water source, each pond, temperature, dissolved oxygen, pH value, water quality physical and chemical index are identical, management level are consistent, the Prawn material that feedstuff selected stars feed companies produces.Duration of test on June 10th, 2013, June 20 found pathological changes, confirmed as after diagnosing: taura syndrome virus (TSV) to August 20.
Get the pharmaceutical composition D for preparing to mix by 1 kilogram of shrimp daily dose and raise (bait) material by every 1 kg body weight daily dose and to throw something and feed 24.5-49 mg, No. 1 pond is used in conjunction 3 days, and No. 3 ponds are used in conjunction 5 days, mixes to raise (bait) material and throw something and feed.
No. 2, No. 4 ponds are mixed by 1 kilogram of shrimp daily dose and are raised (bait) material and to throw something and feed florfenicol 15mg, and No. 2 ponds are used in conjunction 3 days, and No. 4 ponds are used in conjunction 5 days.
No. 5, No. 6 pond not medications.
Received shrimp situation on August 20 in table 4.
Table 4 is tested each pond and is received shrimp situation statistics
Remarks: because shrimp life habit is special, not easily observe in pond bottom, and after death decompose very soon, cannot determine the accurate quantity of dead shrimp at experimental session.
More than experiment shows: the antibiotics prawn taura syudrome such as florfenicol, without positive effect, and do not use antibacterials without significant difference, and pharmaceutical composition D prawn taura syudrome has remarkable result, and protective rate is up to more than 80%.
Experiment 5
1), the preparation of pharmaceutical composition H: get ciprofloxacin (ofloxacin) 20-40 weight portion, berberine 4.5-9 weight portion mixes.
2) tarda, is treated sick
Choose 300 square metres of cement pits 6 mouthfuls, experiment pool is made in No. 1, No. 3 ponds, and No. 2, No. 4 ponds compare pond, and No. 5, No. 6 ponds do blank group, the depth of water 1.2 meters, water source, each pond, water quality physical and chemical index are identical, and management level are consistent, and Trionyx sinensis Wiegmann 150 is put in every pond, the frog 30, tilapia 100 tail, logical prestige trionyx sinensis feed selected by feedstuff to duration of test to August 30 on May 30th, 2013.
Found that Trionyx sinensis Wiegmann is sick on July 3, July 4 frog, tilapia is sick, being separated with determining discovery from Trionyx sinensis Wiegmann, the frog, tilapia lesions position is respectively same cause of disease: tarda (Edwardsiella lctalarus).
Started July 4 to get it filled compositions H by every 1 kg body weight Trionyx sinensis Wiegmann, the frog, tilapia daily dose, by every 1 kg body weight Trionyx sinensis Wiegmann, the frog, tilapia 24.5-49mg, No. 1 pond is used in conjunction 5 days, and No. 3 ponds are used in conjunction 7 days.
No. 2, No. 4 ponds are got ciprofloxacin (ofloxacin) 40-80mg be used in conjunction 5-7 days by every 1 kg body weight Trionyx sinensis Wiegmann, the frog, tilapias.
No. 5, No. 6 pond not medications.
On July 4 to 11 each pond Trionyx sinensis Wiegmann, the frog, tilapia necrology is in table 5
Table 5
Prove that the tarda disease of pharmaceutical composition H to Trionyx sinensis Wiegmann, the frog, tilapia etc. has significant curative effect from above experiment.
Claims (6)
1. prevent and treat a pharmaceutical composition for aquatic animal disease, this pharmaceutical composition preventing and treating aquatic animal viral disease is made up of following two kinds of compositions: quinolone antibiotic and berberine.
2. the pharmaceutical composition preventing and treating aquatic animal disease according to claim 1, is characterized in that: described quinolone antibiotic: berberine weight ratio is 10-40:3.3-9.
3. the pharmaceutical composition preventing and treating aquatic animal disease according to claim 1, is characterized in that: described quinolone antibiotic is norfloxacin, enrofloxacin, ofloxacin or ciprofloxacin.
4. the pharmaceutical composition preventing and treating aquatic animal disease according to claim 3, is characterized in that: described norfloxacin is Norfloxacin Lactate, norfloxacin nicotinate or norfloxacin hydrochloride; Described ciprofloxacin is ciprofloxacin, ciprofloxacin lactate or nicotinic acid ciprofloxacin.
5. the pharmaceutical composition preventing and treating aquatic animal disease according to claim 1, is characterized in that: described berberine is berberine hydrochloride or berberine sulfate.
6. the purposes of preventing and treating the pharmaceutical composition of aquatic animal disease described in the arbitrary claim of claim 1-5: this pharmaceutical composition for preventing and treating research of hemorrhage of grass carp, fulminant hemorrhagic disease, crucian carp Simplex Virus, Fructus Persicae draw syndrome virus or tarda is sick.
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| CN101347432A (en) * | 2008-09-05 | 2009-01-21 | 郑州后羿制药有限公司 | Long-acting enrofloxacin injection for livestock and poultry and method of preparing the same |
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