CN106580994A - Enrofloxacin hydrochloride composition and liquid medicine, and preparation methods thereof - Google Patents

Enrofloxacin hydrochloride composition and liquid medicine, and preparation methods thereof Download PDF

Info

Publication number
CN106580994A
CN106580994A CN201611169901.9A CN201611169901A CN106580994A CN 106580994 A CN106580994 A CN 106580994A CN 201611169901 A CN201611169901 A CN 201611169901A CN 106580994 A CN106580994 A CN 106580994A
Authority
CN
China
Prior art keywords
silkworm
enrofloxacin
septicaemia
enrofloxacin hcl
medicinal liquid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201611169901.9A
Other languages
Chinese (zh)
Inventor
吴洪丽
孙波
周洪英
郝瑜
叶建美
许淑琼
吴康
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institute of Economic Crop of Hubei Academy of Agricultural Science
Original Assignee
Institute of Economic Crop of Hubei Academy of Agricultural Science
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Institute of Economic Crop of Hubei Academy of Agricultural Science filed Critical Institute of Economic Crop of Hubei Academy of Agricultural Science
Priority to CN201611169901.9A priority Critical patent/CN106580994A/en
Publication of CN106580994A publication Critical patent/CN106580994A/en
Pending legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses an enrofloxacin hydrochloride composition and a liquid medicine, and preparation methods thereof, and relates to the field of application of enrofloxacin hydrochloride. The composition comprises, by mass, 2.5-10% of enrofloxacin hydrochloride and 90-97.5% of a water-soluble pharmaceutic adjuvant. Added is added to the enrofloxacin hydrochloride composition to prepare the liquid medicine, and the concentration of the enrofloxacin hydrochloride in the liquid medicine is 250-1000 mg/L; and the liquid medicine is sprinkled on mulberry leaves to obtain medicinal leaves, and the medicinal leaves are used to feed bombyx mori in order to control black chest septicaemia and serratial septicemia of the bombyx mori. The liquid medicine can simultaneously control the black chest septicaemia and serratial septicemia of the bombyx mori, has a better bombyx mori black chest septicaemia control effect than a traditional medicine erythromycin thiocyanate, and has an obvious bombyx mori serratial septicemia control effect than a traditional medicine enrofloxacin hydrochloride.

Description

Enrofloxacin HCL compositionss, medicinal liquid and preparation method
Technical field
The present invention relates to the application of Enrofloxacin HCL, and in particular to a kind of Enrofloxacin HCL compositionss, medicinal liquid And preparation method.
Background technology
Silkworm industry occupies critical role in national economy.Affect current China's Silk Industry overall economic benefit it is many because In element, silkworm evil of being critically ill is one of principal element.According to incompletely statistics, China current silkworm disease loss rate is 15% or so, by current China produces 440000 tons of cocoon meter per year, every year because silkworm disease damage loses up to 60,000 tons or so of Bombyx bombycis, is worth more than 800,000,000 yuan, and because silkworm is critically ill evil Cause silk quality low, the loss caused to whole industry is just more difficult to estimate.
In common silkworm disease, bacterial diseases are long-term existence and endanger one of serious disease, and its loss rate accounts for silkworm disease loss rate More than 20%, due to the seriousness of its liability, complexity and harm, the effective preventing and treating to bacterial diseases, be always silkworm The emphasis of sick prevention and control research field.Septicaemia and clever bacterium septicemia are all common silkworm diseases, in addition to the ovum phase, larva, pupa, 3 stages of development of moth can occur, and summer autumn silkworm rearing season is more universal.Black breast deteriorated blood bacterium, clever bacterium and blue or green head deteriorated blood bacterium are the masters of primary disease Want pathogenetic bacteria.In the market, the common drug for treating silkworm septicaemia is sulfur hydracid erythromycin, treats silkworm spirit bacterium Septicemia common drug is ciprofloxacin, on the one hand, sulfur hydracid erythromycin and ciprofloxacin are to the black breast deteriorated blood of silkworm Disease and the septicemic cemia therapeutic effect of clever bacterium are not fine, and when concentration is 200mg/L, therapeutic effect only reaches 85.59%, improves and uses Concentration easily causes the side effect such as Drug resistance, and with the increase of service life, its prevention effect can be gradually lowered;The opposing party Face, as silkworm Jing often suffers from silkworm septicaemia and clever bacterium septicemia simultaneously, and do not have on market can and meanwhile prevent and Two kinds of sick medicines for the treatment of.
The content of the invention
The invention aims to overcome the shortcomings of above-mentioned background technology, there is provided a kind of Enrofloxacin HCL compositionss, Medicinal liquid and preparation method, the present invention can prevent and treat septicaemia and clever bacterium septicemia simultaneously, and, the present invention is to black The septicemic cemia prevention effect of breast is substantially better than conventional medicament sulfur hydracid erythromycin, and the septicemic cemia prevention effect of clever bacterium is substantially better than Conventional medicament ciprofloxacin.
The present invention provides a kind of for preventing and treating silkworm septicaemia and the septicemic cemia Enrofloxacin HCL compositionss of clever bacterium, By percentage to the quality, said composition is used by 2.5%~10% Enrofloxacin HCL and 90%~97.5% water-soluble pesticide Adjuvant is constituted.
On the basis of above-mentioned technical proposal, by percentage to the quality, the compositionss by 5% Enrofloxacin HCL and 95% water solublity pharmaceutic adjuvant composition.
On the basis of above-mentioned technical proposal, the water solublity pharmaceutic adjuvant is monosaccharide or soluble polysaccharide.
On the basis of above-mentioned technical proposal, the water solublity pharmaceutic adjuvant is Lactose, glucose, in soluble starch Any one.
The present invention provides the preparation method of above-mentioned Enrofloxacin HCL compositionss, comprises the following steps:
By percentage to the quality, the water-soluble pesticide of 2.5%~10% Enrofloxacin HCL and 90%~97.5% is used Adjuvant is mixed, and obtains Enrofloxacin HCL compositionss.
The present invention provides a kind of for preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, it is characterised in that:Should Medicinal liquid is made using the Enrofloxacin HCL compositionss as any one of Claims 1-4, hydrochloric acid grace promise in the medicinal liquid The concentration of Sha Xing is 250~1000mg/L.
On the basis of above-mentioned technical proposal, the concentration of the middle Enrofloxacin HCL is 500mg/L.
The present invention provides the above-mentioned preparation method for preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, including Following steps:
A certain amount of Enrofloxacin HCL compositionss are taken, is added water and is configured to medicinal liquid, hydrochloric acid En Nuosha in the medicinal liquid The concentration of star is 250~1000mg/L.
On the basis of above-mentioned technical proposal, in the medicinal liquid, the concentration of Enrofloxacin HCL is 500mg/L.
Compared with prior art, advantages of the present invention is as follows:
(1) compositionss that the present invention is provided can play prevention simultaneously to silkworm septicaemia and clever bacterium septicemia and control Therapeutic effect, it is simple, efficient, practical, wrong medicine is not resulted in, so as to delay treatment, causes Bombyx bombycis to lose, to reducing silkworm disease damage Lose significant.
(2) present invention is substantially better than conventional medicament to silkworm septicaemia and the septicemic cemia prevention and treatment effect of clever bacterium Sulfur hydracid erythromycin and ciprofloxacin, can further reduce silkworm disease loss rate, improve cocoon yield and quality.Jing drug effects Test proves that Enrofloxacin HCL is respectively 99.67% He to silkworm septicaemia and the septicemic cemia effective percentage of clever bacterium 99.50%, total effective rate is 99.17%, respectively higher than the effective percentage of erythromycin thiocyanate, ciprofloxacin, and there is pole Significant difference.
Specific embodiment
With reference to specific embodiment, the present invention is described in further detail.
The embodiment of the present invention provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia Enrofloxacin HCL combination of clever bacterium Thing, by percentage to the quality, said composition by 2.5%~10% Enrofloxacin HCL and 90%~97.5% water-soluble pesticide Constituted with adjuvant.Preferably, said composition is made up of 5% Enrofloxacin HCL and 95% water solublity pharmaceutic adjuvant.It is water-soluble Property pharmaceutic adjuvant can be monosaccharide or soluble polysaccharide, for example, can be Lactose, glucose, any in soluble starch One kind, as Lactose can improve taking food property of the silkworm to medicine leaf, and lactose stabilized is preferably, is difficult the moisture absorption, therefore, it is water-soluble Property pharmaceutic adjuvant is preferably Lactose.
The preparation method of above-mentioned Enrofloxacin HCL compositionss is:By percentage to the quality, by 2.5%~10% hydrochloric acid Enrofloxacin and 90%~97.5% water solublity pharmaceutic adjuvant are mixed, and obtain Enrofloxacin HCL compositionss.
The embodiment of the present invention also provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, and the medicinal liquid contains The concentration of Enrofloxacin HCL is 250~1000mg/L, preferably 500mg/L.Its preparation method is:Take a certain amount of above-mentioned salt Sour enrofloxacin compositionss, add water and are configured to medicinal liquid, and in the medicinal liquid, the concentration of Enrofloxacin HCL is 250~1000mg/L, Preferably 500mg/L;
The using method of the medicinal liquid is:By medicine liquid spray on Folium Mori, medicine leaf is obtained, using medicine leaf feeding silkworm, be used for Silkworm septicaemia and clever bacterium septicemia are prevented and treated simultaneously.Wherein, the detailed process using medicine leaf feeding silkworm is as follows:In health The 3rd day, first day of the 5th age and the 3rd day of the 4th age of silkworm larva, each feeding medicine leaf of upper cluster the previous day once, feed every time The time of food is 6h;When finding to have silkworm infection septicemia pathogenic bacterium, find infected silkworm first day to whole silkworms Continuous feeding medicine leaf three times, the time of each feeding is 8h, and once, the time of each feeding is 6h to daily feeding medicine leaf later.
Below by 7 specific embodiments, the present invention is described in detail.
Embodiment 1:
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia Enrofloxacin HCL compositionss of clever bacterium, with Mass percent meter, said composition are mixed by 5% Enrofloxacin HCL and 95% Lactose.
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, and its preparation method is:Take 5g Enrofloxacin HCL compositionss (hydrochloric enrofloxacin 250mg) are dissolved in 500ml water, obtain prevent and treat silkworm septicaemia and The septicemic cemia medicinal liquid of clever bacterium, in medicinal liquid, Enrofloxacin HCL concentration is 500mg/L.
Embodiment 2:
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia Enrofloxacin HCL compositionss of clever bacterium, with Mass percent meter, said composition are mixed by 5% Enrofloxacin HCL and 95% Lactose.
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, and its preparation method is:Take 5g Enrofloxacin HCL compositionss (hydrochloric enrofloxacin 250mg) are dissolved in 1000ml water, obtain preventing and treating silkworm septicaemia With the septicemic cemia medicinal liquid of clever bacterium, in medicinal liquid, Enrofloxacin HCL concentration is 250mg/L.
Embodiment 3:
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia Enrofloxacin HCL compositionss of clever bacterium, with Mass percent meter, said composition are mixed by 5% Enrofloxacin HCL and 95% Lactose.
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, and its preparation method is:Take 5g Enrofloxacin HCL compositionss (hydrochloric enrofloxacin 250mg) are dissolved in 250ml water, obtain prevent and treat silkworm septicaemia and The septicemic cemia medicinal liquid of clever bacterium, in medicinal liquid, Enrofloxacin HCL concentration is 1000mg/L.
Embodiment 4:
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia Enrofloxacin HCL compositionss of clever bacterium, with Mass percent meter, said composition are mixed by 2.5% Enrofloxacin HCL and 97.5% Lactose.
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, and its preparation method is:Take 5g Enrofloxacin HCL compositionss (hydrochloric enrofloxacin 250mg) are dissolved in 500ml water, obtain prevent and treat silkworm septicaemia and The septicemic cemia medicinal liquid of clever bacterium, in medicinal liquid, Enrofloxacin HCL concentration is 500mg/L.
Embodiment 5:
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia Enrofloxacin HCL compositionss of clever bacterium, with Mass percent meter, said composition are mixed by 10% Enrofloxacin HCL and 90% Lactose.
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, and its preparation method is:Take 5g Enrofloxacin HCL compositionss (hydrochloric enrofloxacin 250mg) are dissolved in 500ml water, obtain prevent and treat silkworm septicaemia and The septicemic cemia medicinal liquid of clever bacterium, in medicinal liquid, Enrofloxacin HCL concentration is 500mg/L.
Embodiment 6:
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia Enrofloxacin HCL compositionss of clever bacterium, with Mass percent meter, said composition are mixed by 5% Enrofloxacin HCL and 95% glucose.
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, and its preparation method is:Take 5g Enrofloxacin HCL compositionss (hydrochloric enrofloxacin 250mg) are dissolved in 500ml water, obtain prevent and treat silkworm septicaemia and The septicemic cemia medicinal liquid of clever bacterium, in medicinal liquid, Enrofloxacin HCL concentration is 500mg/L.
Embodiment 7:
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia Enrofloxacin HCL compositionss of clever bacterium, with Mass percent meter, said composition are mixed by 10% Enrofloxacin HCL and 90% soluble starch.
The present embodiment provides a kind of preventing and treating silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, and its preparation method is:Take 5g Enrofloxacin HCL compositionss (hydrochloric enrofloxacin 250mg) are dissolved in 500ml water, obtain prevent and treat silkworm septicaemia and The septicemic cemia medicinal liquid of clever bacterium, in medicinal liquid, Enrofloxacin HCL concentration is 500mg/L.
The principle of the present invention is explained with 5 tests below.
Test 1:Drug screening test
The common antibacterials in market are chosen as reagent is supplied, silkworm septicaemia and the pathogenic thalline of clever bacterium septicemia is carried out Outer bacteriostatic test.Bacteria suspension is made using 20ml aseptic water washing lawns by every antibacterial inclined-plane to experimental study, it is double-deck Method is down flat plate, and lower floor's blank meat soup (MH) culture medium adds 1% (V/V) bacteria suspension, in every Oxford cup in the MH culture medium of upper strata 200 μ l are added for the solution (drug level is 50mg/L) of reagent thing.37 DEG C of overnight incubations, it is transparent aseptic around measurement Oxford cup Loop diameter size, per group of test are parallel three times, and record data is averaged, statistical analysiss antibacterial effect respectively for reagent thing Really.As shown in table 1.1:
Table 1.1, for reagent thing inhibition zone test result (diameter:mm)
Shown according to 1.1 interpretation of result of table, black breast deteriorated blood bacterium antibacterial circle diameter is with enrofloxacin maximum (25.27mm), high In control erythromycin thiocyanate (20.72mm);Clever bacterium deteriorated blood bacterium antibacterial circle diameter is maximum with compound sulfadiazine sodium (30.29mm), higher than control ciprofloxacin (25.91mm), but all it is effectively hydrochloric acid grace to two kinds of bacterium fungistatic effects Promise sand star, its antibacterial circle diameter is 24.94mm and 28.22mm, is above control drug, also, Enrofloxacin HCL is water-soluble Property medicine, meet silkworm antibacterials requirement.
Test 2:Adjuvant screening test
These three adjuvant dissolubilities of Lactose, glucose, soluble starch and color and luster meet soluble powder formulation requirements, but Glucose powder and the easy moisture absorption of soluble starch, Lactose are difficult the moisture absorption, stability preferably, accordingly, it is determined that Lactose be this preparation most Good compatibility adjuvant.
Comparative study is carried out to the proportioning of Enrofloxacin HCL and Lactose, Enrofloxacin HCL is carried out in proportion with Lactose Dispensing, is then made into the medicinal liquid of the 500mg/L in terms of Enrofloxacin HCL, in the ratio sprinkling Mulberry of 500ml medicine liquid spray 5kg Folium Mori Leaf, then Folium Mori are raised into silkworm, as a result as shown in table 2.1.
The proportioning result of table 2.1, Enrofloxacin HCL and Lactose
From table 2.1 as can be seen that Lactose can improve taking food property of the silkworm to medicine leaf, Enrofloxacin HCL is more beneficial for Absorb and utilize.Lactose content more than 95%, can promote to eat Mulberry 10%, therefore select lactose content >=95%, in order to ensure medicine Effect, proportioning are preferably Enrofloxacin HCL 5%, Lactose 95%.
Test 3:Enrofloxacin HCL dose screening is tested
To the silkworm inoculating strain of health so that silkworm infected silkworm septicaemia and clever bacterium septicemia, by sense The Folium Mori of variable concentrations trial drug and control drug, and then relative analyses trial drug and control were sprayed in the silkworm feed of dye Therapeutic effect of the medicine to silkworm, and then filter out suitable drug level.
Test organismss are inoculated on nutrient agar slant medium and cultivate 24h, during test, by 2ml aseptic water washing lawns Bacteria suspension is made, black breast deteriorated blood bacterium dilutes 10 times, and clever bacterium dilutes 100 times.Dipped with the Inoculating needle of Jing alcohol burner flame sterilizations few Amount bacterium solution is to percutaneous puncture-inoculation under silkworm body surface from 5 ages.Start medicine feed leaf after terminating from inoculation, 24 hours whole medicine feeds in the 1st day Leaf, the 2nd, 3 days difference medicine feed leaves 6 hours.Silkworm is grouped and Folium Mori classification is referring to table 3.1.
Table 3.1, the test of Enrofloxacin HCL dose screening
Investigated according to the symptom that test silkworm morbidity is dead.I.e.:Septicaemia silkworm has just stubbornly refused long chest blackening, after rear Expand to whole body;After death whole body is rubescent soon for clever bacterium septicemia.Death rate of the onset in positive controls investigation statisticses 72 hours, It is dead that administration treatment group continues raising investigation morbidity in 48 hours in addition to the Affected individuals number during investigation administration, after the administration is complete Die silkworm number, add up to total morbidity number, be calculated as follows protective rate.Test is repeated 3 times, statistical average protective rate.
Drug effect judgment basis Ministry of Agriculture veterinary drug evaluation center《Veterinary drug investigative technique guideline collects (2006-2011)》 Regulation in page 131~132 " silkworm antimicrobial drug evaluating drug effect experimental technique guideline ", carries out drug effect judgement.Tool Body is:Positive controls death rate of the onset >=95.0%, judges the antimicrobial drug with average protective rate >=90.0% of medicine group Thing treatment is effective.
Using infected silkworm of the feeding without medicine Folium Mori as positive control, to be uninfected by silkworm as negative control, test knot Fruit and analysis are referring to table 3.2:
The prevention effect of table 3.2, Enrofloxacin HCL compositionss to silkworm septicaemia
Table 3.3, Enrofloxacin HCL compositionss are to the septicemic cemia prevention effect of silkworm spirit bacterium
Referring to shown in table 3.2~3.3, bacterium is septicemic cemia prevents and treats result to silkworm septicaemia and spirit for Enrofloxacin HCL Show, 500, the prevention effect of concentration 2 kinds of bacteremic septicemias above-mentioned to silkworm of 1000mg/L more than 90%, 125, The prevention effect of the concentration of 250mg/L 2 kinds of bacteremic septicemias above-mentioned to silkworm is below 90%, and test repeatability is good.
Test 4:Therapeutic effect is tested
To the silkworm inoculating strain of health so that silkworm infects septicaemia and clever bacterium septicemia, by sense simultaneously The silkworm feed sprinkling overtesting medicine and the Folium Mori of control drug of dye, and then relative analyses trial drug and control drug are to family The therapeutic effect of silkworm.Detailed process is as follows:
Test organismss are inoculated on nutrient agar slant medium and cultivate 24h, during test, by 2ml aseptic water washing lawns Bacteria suspension is made, black breast deteriorated blood bacterium dilutes 10 times, and clever bacterium dilutes 100 times.Dipped with the Inoculating needle of Jing alcohol burner flame sterilizations few Amount bacterium solution is to percutaneous puncture-inoculation under silkworm body surface from 5 ages.Start medicine feed leaf after terminating from inoculation, 24 hours whole medicine feeds in the 1st day Leaf, the 2nd, 3 days difference medicine feed leaves 6 hours.Require according to silkworm pharmacodynamic study, silkworm is grouped and Folium Mori classification such as 4.1 institute of table Show.
Table 4.1, test silkworm grouped table
Medication is referred to《Veterinary drug national standard collects》First (compiling within 2010 at Ministry of Agriculture's veterinary drug evaluation center) page 64 Enrofloxacin solution (silkworm use).Take respectively Enrofloxacin HCL compositionss 10g (hydrochloric enrofloxacin 0.5g) be dissolved in 2000, 1000th, 500ml water, be made into concentration be 250,500, the medicinal liquid of 1000mg/L, take each 500ml of above-mentioned medicinal liquid and spray Folium Mori 5kg;Take sulfur Cyanic acid erythromycin (silkworm use) 1 (50mg), is dissolved in 500ml water, takes Ciloxan (silkworm use) (2ml:50mg)5 , 500ml water is dissolved in, above-mentioned 2 kinds of solution 500ml are taken respectively, each spray Folium Mori 5kg during sprinkling with Folium Mori tow sides moistening is Degree.Design from inoculation by test group and after terminating, start medicine feed leaf, the 1st day, feed medicine leaf 24 hours, difference feed on the the 2nd and the 3rd Medicine leaf 6 hours, remaining time feed common Folium Mori.
Investigated according to the symptom that test silkworm morbidity is dead.I.e.:Septicaemia silkworm has just stubbornly refused long chest blackening, after rear Expand to whole body;After death whole body is rubescent soon for clever bacterium septicemia.Death rate of the onset in positive controls investigation statisticses 72 hours, It is dead that administration treatment group continues raising investigation morbidity in 48 hours in addition to the Affected individuals number during investigation administration, after the administration is complete Die silkworm number, add up to total morbidity number, be calculated as follows protective rate.Test is repeated 3 times, statistical average protective rate.
Drug effect judgment basis Ministry of Agriculture veterinary drug evaluation center《Veterinary drug investigative technique guideline collects (2006-2011)》 Regulation in page 131~132 " silkworm antimicrobial drug evaluating drug effect experimental technique guideline ", carries out drug effect judgement.Tool Body is:Positive controls death rate of the onset >=95.0%, judges the antimicrobial drug with average protective rate >=90.0% of medicine group Thing treatment is effective.
Enrofloxacin HCL compositionss are to the therapeutic effect and significance difference analysis of silkworm septicaemia referring to table 4.2 And shown in table 4.3:
The therapeutic effect of table 4.2, Enrofloxacin HCL compositionss to silkworm septicaemia
Table 4.3, Enrofloxacin HCL compositionss are to silkworm septicaemia protective rate significance difference analysis
From table 4.2 and table 4.3, positive control death rate of the onset > 95%, 500mg/L, 1000mg/L group are averagely protected Shield rate is more than 90%, and compares higher than erythromycin thiocyanate.Protective rate analysis result shows, 250mg/L, 500mg/L, There is pole significant difference between 1000mg/L concentration group and the control of sulfur hydracid erythromycin.
Enrofloxacin HCL compositionss the silkworm septicemic cemia therapeutic effect of spirit bacterium and significance difference analysis are shown in Table 4.4 and Table 4.5.
Table 4.4, Enrofloxacin HCL compositionss are to the septicemic cemia prevention effect of silkworm spirit bacterium
Table 4.5, Enrofloxacin HCL compositionss are to silkworm spirit bacterium septicemia protective rate significance difference analysis
Referring to shown in table 4.4 and table 4.5, Enrofloxacin HCL compositionss are to the septicemic cemia clinical test results of silkworm spirit bacterium Show, positive control death rate of the onset > 95%, the average protective rate of 500mg/L, 1000mg/L group is more than 90%, and is higher than sulfur cyanogen Sour erythromycin control.Protective rate analysis result shows, is not significantly different between 500mg/L and 1000mg/L concentration groups, they There is pole significant difference to 250mg/L concentration groups, there were significant differences to ciprofloxacin group for 500mg/L concentration group, does not extremely show Difference is write, 1000mg/L concentration group has pole significant difference to ciprofloxacin control.
Enrofloxacin HCL 500mg/L trial zones to the protective rate of silkworm septicaemia up to 92.56%, to clever bacterium deteriorated blood The protective rate of disease is above control drug, is the least concentration of protective rate > 90% 91.94%.Therefore, Enrofloxacin HCL Recommended dose be set to 500mg/L.
Test 5:Experiment of preventive effects
Test silkworm is raised under normal conditions, natural occurrence.By to silkworm feed sprinkling overtesting medicine and control The Folium Mori of medicine, and then the preventive effect of relative analyses trial drug and control drug to silkworm.
Drug effect checkout procedure adopts 3 test groups and 1 matched group:Enrofloxacin HCL compositionss test group uses medicament (counting with Enrofloxacin HCL) is measured as 500mg/L, silkworm septicaemia clinical trial matched group medicine erythromycin thiocyanate group Dosage be 100mg/L, the dosage of silkworm spirit bacterium septicemia clinical trial control drug ciprofloxacin group is 500mg/L, matched group are clear water matched group.Repeat 3rd area, per 200, area silkworm.
Investigational agent 500ml water is taken, Folium Mori 5kg is sprayed, is added food to silkworm.The 3rd day the 4th age of healthy silkworm larva, the 5th First day age and the 3rd day, each medicine feed leaf of upper cluster the previous day once, each feeding time 6h;When sick silkworm is found, first day even Continuous adding eats three times, per 8h once, once a day later, each feeding time 6h.
Investigated according to the dead symptom of test silkworm morbidity before feeding leaf every morning, i.e.,:Septicaemia is just stubbornly refused by silkworm Chest blackening, expands to whole body after long;After death whole body is rubescent soon for clever bacterium septicemia, and the morbidity for recording above-mentioned 2 kinds of silkworms disease is dead Die number, for the silkworm of above-mentioned disease carries out the isolation identification of pathogenic bacterium, confirm as could counting for correspondence pathogenic bacterium.Control time Start to being only placed on small straw bundles to spin cocoons for four-aged silkworm.Death rate of the onset and protective rate are investigated before being placed on small straw bundles to spin cocoons.
It is calculated as follows protective rate.Test is repeated 3 times, statistical average protective rate.
Table 5.1, septicaemia silkworm pathogenic bacterium isolation identification result
Table 5.2, clever bacterium septicemia silkworm pathogenic bacterium isolation identification result
Table 5.3, various medicines are to the septicemic cemia protective rate of silkworm
Table 5.4, various medicines are to silkworm septicaemia protective rate significance difference analysis
Table 5.5, various medicines are to silkworm spirit bacterium septicemia protective rate significance difference analysis
Various medicines are calculated in table 5.3 to the septicemic cemia protective rate result of silkworm according to the data of table 5.1~5.2. Referring to shown in table 5.3, with Enrofloxacin HCL to the septicemic cemia protective rate highest of silkworm, which is to the average protective rate of septicaemia For 99.67%, be 99.50% to the average protective rate of clever bacterium septicemia, total protective rate is 99.17%, higher than erythromycin thiocyanate, Ciprofloxacin and clear water control.Referring to shown in table 5.4~5.5, significance difference analysis show that Enrofloxacin HCL group is protected Shield rate shows significant difference and pole significant difference to other all matched groups.
Silkworm to be tested is placed on small straw bundles to spin cocoons after harvesting of cocoon and carries out Bombyx bombycis economic characters investigation, that is, investigate amount of cocoon crop, cocoon weight, cocoon shell weight, cocoon Layer rate, dead cage rate, investigate impact of the medicine to Bombyx bombycis economic characters.
Table 5.6, Cocoon Quality Traits is investigated
Table 5.7, cocoon weight significance difference analysis
Table 5.8, cocoon shell weight significance difference analysis
Table 5.9, Cocoon layer ratio significance difference analysis
Referring to shown in 5.6~table of table 5.9, the survey showed that for Cocoon Quality Traits, and Enrofloxacin HCL is in cocoon weight, cocoon layer Compare with each drug control and clear water in terms of amount, Cocoon layer ratio and there is no significant difference.
The principle of the present invention is described below:
, used as model insects, its metabolic studies is clearly, complete with aquatic animal, birds, mammal for silkworm It is complete different.In silkworm itself and silkworm body, the sensitivity of Pathogens is also entirely different, and silkworm is just meaned once falling ill Death, prevention silkworm disease is the most important thing.
At present, existing correlational study proves that enrofloxacin compositionss can be used in treating bacterial silkworm septicemia, Patent No. CN102000092A discloses the compositionss that a kind of sulfadiazine sodium is formed with enrofloxacin, trimethoprim, is used for Bacterial silkworm septicemia is treated in prevention.Wherein, enrofloxacin is water insoluble, need to be made into during use turbid liquid spraying in Silkworm is fed on Folium Mori, affects taking food property of the silkworm to medicine leaf, enrofloxacin to be difficult to be absorbed and used into after silkworm body, and in the short time Interior enteral road is excreted with feces, as a result causes enrofloxacin not high in silkworm body absorption rate and blood drug concentration, its point Sub- state is also unfavorable for which plays antibacterial effect, thus to preventing or treating bacterial silkworm septicemia effect on driving birds is not good.Need Compositionss are formed with other drugs, be can be only achieved while preventing and treating the effect of silkworm septicaemia bacterium and clever bacterium deteriorated blood pathogenic bacteria Really.
Enrofloxacin HCL is used to prevent or treat bacterial silkworm septicemia and have no to have been reported that.Enrofloxacin HCL It is similar with enrofloxacin antibacterial effect, but physicochemical property is entirely different, and its using method and use range are also different.Therefore, grind Enrofloxacin HCL is studied carefully while to septicaemia bacterium and the antibacterial effect and using dosage of clever bacterium deteriorated blood pathogenic bacteria, to silkworm antibacterial Property septicemia prevention and treatment it is most important.
The present invention provides a kind of Enrofloxacin HCL compositionss, medicinal liquid and preparation method, with Enrofloxacin HCL as activity Composition, mass content are 5%, add adjuvant Lactose, and mass content is 95%.The Main Function of Lactose is filler, is not affected The stability and curative effect of crude drug, while during administration soluble in water, can adhere on unique food Folium Mori of silkworm, and promote Silkworm is taken food to Enrofloxacin HCL medicine leaf.The present invention provides a kind of new application of Enrofloxacin HCL, specifically refers to hydrochloric acid Enrofloxacin prevents and treats silkworm septicaemia and the purposes in clever bacterium septicemia medicine at the same time.Enrofloxacin HCL one As be used for bacterial other Animal diseases for the treatment of, use it for preventing and treating silkworm septicaemia and clever bacterium deteriorated blood Disease is had no precedent in prior art.In prior art, the conventional medicine of silkworm septicaemia and clever bacterium septicemia is treated Respectively erythromycin thiocyanate and ciprofloxacin, and Enrofloxacin HCL has to silkworm septicaemia and clever bacterium septicemia Effect is prevented and treated preferably.According to above-mentioned purposes, Enrofloxacin HCL compositionss, medicinal liquid and preparation method are being applied When, it is configured to the aqueous solution that hydrochloric enrofloxacin concentration is 500mg/L.
Present invention research finds that absorbance is higher after Enrofloxacin HCL enters bombyx mori intestinal, soluble in water due to which, enters Exist in ionic condition after entering silkworm body, blood drug concentration is persistently raised, eliminate relatively slow after reaching peak value, when can remain longer Between fungistatic effect.In the present invention, adjuvant Lactose can improve taking food property of the silkworm to medicine leaf, be more beneficial for Enrofloxacin HCL Absorption and utilization.
The compositionss that the present invention is provided have preferable effect to preventing and treating silkworm septicaemia and clever bacterium septicemia, Enrofloxacin HCL and Lactose are taken, aqueous solution is made into according to mass content, wherein hydrochloric enrofloxacin 500mg/L, Lactose 9500mg/L, is sprayed on Folium Mori and feeds silkworm, and the Jing tests of pesticide effectiveness are proved, Enrofloxacin HCL is lost to silkworm septicaemia and clever bacterium The effective percentage of disorders of blood is respectively 99.67% and 99.50%, and total effective rate is 99.17%, higher than erythromycin thiocyanate, hydrochloric acid ring Third husky star control, and there is pole significant difference.
Why the Enrofloxacin HCL compositionss of the present invention, medicinal liquid and preparation method are to silkworm septicaemia and clever bacterium Septicemia has preferable curative effect, is because the third generation carbostyril family antibacterial drugs that Enrofloxacin HCL is synthesis, also known as ethyl Ciprofloxacin, enrofloxacin.On October 4th, 1996 obtains FDA approvals, is poultry and the special carbostyril family antibacterial drugs of Aquatic product.I State was registered as novel chiral synthon in 2010, had been widely used in veterinary clinic.With broad spectrum antibiotic activity, with very strong infiltration Property, oral absorption is good, and blood drug level is high and stable, and its metabolite is Ciprofloxacin, still has powerful antibacterial action.Medicine is direct The nucleus of antibacterial are acted on, is suppressed DNA of bacteria gyrase, is caused antibacterial quick death, be not likely to produce drug resistance.It is anti-with other Rhzomorph is without cross resistance.In addition, Enrofloxacin HCL and adjuvant do not affect taking food property of the silkworm to unique food Folium Mori. As Folium Mori are entered after bombyx mori intestinal, can excrete at short notice, Enrofloxacin HCL can be quickly absorbed into by silkworm Silkworm body simultaneously plays a role.
Those skilled in the art can carry out various modifications and variations to the embodiment of the present invention, if these modifications and change Within the scope of the claims in the present invention and its equivalent technologies, then these modifications and modification are also in protection scope of the present invention for type Within.
The prior art that the content not described in detail in description is known to the skilled person.

Claims (9)

  1. It is 1. a kind of to be used to prevent and treat silkworm septicaemia and the septicemic cemia Enrofloxacin HCL compositionss of clever bacterium, it is characterised in that: By percentage to the quality, said composition is used by 2.5%~10% Enrofloxacin HCL and 90%~97.5% water-soluble pesticide Adjuvant is constituted.
  2. 2. it is as claimed in claim 1 to be used to prevent and treat silkworm septicaemia and the septicemic cemia Enrofloxacin HCL combination of clever bacterium Thing, it is characterised in that:By percentage to the quality, the compositionss are used by 5% Enrofloxacin HCL and 95% water-soluble pesticide Adjuvant is constituted.
  3. 3. it is as claimed in claim 1 to be used to prevent and treat silkworm septicaemia and the septicemic cemia Enrofloxacin HCL combination of clever bacterium Thing, it is characterised in that:The water solublity pharmaceutic adjuvant is monosaccharide or soluble polysaccharide.
  4. 4. it is as claimed in claim 3 to be used to prevent and treat silkworm septicaemia and the septicemic cemia Enrofloxacin HCL combination of clever bacterium Thing, it is characterised in that:The water solublity pharmaceutic adjuvant is Lactose, glucose, any one in soluble starch.
  5. 5. the preparation method of Enrofloxacin HCL compositionss as claimed in claim 1, it is characterised in that comprise the following steps:
    By percentage to the quality, by 2.5%~10% Enrofloxacin HCL and 90%~97.5% water solublity pharmaceutic adjuvant Mixed, obtained Enrofloxacin HCL compositionss.
  6. It is 6. a kind of to be used to prevent and treat silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, it is characterised in that:The medicinal liquid is using as weighed Profit requires that the Enrofloxacin HCL compositionss any one of 1 to 4 are made, and in the medicinal liquid, the concentration of Enrofloxacin HCL is 250~1000mg/L.
  7. It is 7. as claimed in claim 6 to be used to prevent and treat silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, it is characterised in that:Institute The concentration for stating middle Enrofloxacin HCL is 500mg/L.
  8. 8. it is used for as claimed in claim 6 preventing and treating the preparation method of silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, its It is characterised by, comprises the following steps:
    A certain amount of Enrofloxacin HCL compositionss are taken, is added water and is configured to medicinal liquid, Enrofloxacin HCL in the medicinal liquid Concentration is 250~1000mg/L.
  9. 9. it is used for as claimed in claim 8 preventing and treating the preparation method of silkworm septicaemia and the septicemic cemia medicinal liquid of clever bacterium, its It is characterised by:In the medicinal liquid, the concentration of Enrofloxacin HCL is 500mg/L.
CN201611169901.9A 2016-12-16 2016-12-16 Enrofloxacin hydrochloride composition and liquid medicine, and preparation methods thereof Pending CN106580994A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201611169901.9A CN106580994A (en) 2016-12-16 2016-12-16 Enrofloxacin hydrochloride composition and liquid medicine, and preparation methods thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201611169901.9A CN106580994A (en) 2016-12-16 2016-12-16 Enrofloxacin hydrochloride composition and liquid medicine, and preparation methods thereof

Publications (1)

Publication Number Publication Date
CN106580994A true CN106580994A (en) 2017-04-26

Family

ID=58601010

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201611169901.9A Pending CN106580994A (en) 2016-12-16 2016-12-16 Enrofloxacin hydrochloride composition and liquid medicine, and preparation methods thereof

Country Status (1)

Country Link
CN (1) CN106580994A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115737567A (en) * 2022-10-19 2023-03-07 湖南中科汇智信息服务有限公司 Enrofloxacin soluble powder capable of reducing bitter taste and preparation method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1600311A (en) * 2003-09-26 2005-03-30 周元铎 Medication in silkworm use for treating bacteriosis and preparation method
CN102000092A (en) * 2010-12-10 2011-04-06 湖北农科生物化学有限公司 New application of sulfadiazine sodium

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1600311A (en) * 2003-09-26 2005-03-30 周元铎 Medication in silkworm use for treating bacteriosis and preparation method
CN102000092A (en) * 2010-12-10 2011-04-06 湖北农科生物化学有限公司 New application of sulfadiazine sodium

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
张安启等: "防治家蚕细菌病药物的筛选", 《山东畜牧兽医》 *
王彦文等: "《省力高效生产实用新技术》", 31 August 2014, 中国农业科学技术出版社 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115737567A (en) * 2022-10-19 2023-03-07 湖南中科汇智信息服务有限公司 Enrofloxacin soluble powder capable of reducing bitter taste and preparation method thereof

Similar Documents

Publication Publication Date Title
CN107308117A (en) A kind of Tilmicosin pre-mixing agent and preparation method thereof
CN109999027B (en) Use of melatonin
CN102697787A (en) Application of ponazuril to prevention and treatment of coccidiosis
CN106580994A (en) Enrofloxacin hydrochloride composition and liquid medicine, and preparation methods thereof
CN102000092B (en) New application of sulfadiazine sodium in preparing medicine for preventing or treating Bombyx mori septicemia
CN106620668A (en) Compound tilmicosin solid dispersing agent and preparation method thereof
CN115192642B (en) Preparation method and application of composite biological preparation with parasiticidal function and containing Brevibacillus laterosporus and fermented traditional Chinese medicine
CN110179756A (en) A kind of tilmicosin micro-capsule preparation and preparation method thereof
CN103918935B (en) A kind of pet food additives
CN104474526A (en) Pharmaceutical composition for treating or/and preventing pet viral diseases and preparation method thereof
CN103524448A (en) Enrofloxacin-saccharin compound
CN101829129B (en) Veterinary compound gentamycin sulfate injection and preparation method thereof
CN106554385B (en) Polypeptide compound and application thereof in livestock and poultry
CN101199520A (en) Beta-Lacetam anti-biotic compound dose for animal containing benemid
CN106539754A (en) Hydrobromic acid antifebrile dichroanone solution and preparation method thereof
CN103222975A (en) Application of enrofloxacin salt in preparation of swine oral preparation
CN106727300A (en) A kind of thiabendazolum supensoid agent and preparation method thereof
CN102813909A (en) Compound doxycycline hydrochloride composition for preventing and treating colibacillosis and chronic respiratory disease of poultry as well as preparation method thereof
CN102805772A (en) Application of coptis chinensis, amur cork-tree bark, Chinese rhubarb and skullcap dysentery inhibiting particles to preparation of medicines for treating intestinal diseases of poultry, and medicinal composition formed by compounding particles
CN102973584B (en) Composition for treating nematodosis in dogs and cats, and preparation method thereof
CN112826797A (en) Novel compound anti-coccidium soluble powder and preparation method thereof
CN105617353A (en) Oral administration composition of colistin
CN109364089A (en) It is a kind of with the composition and preparation method thereof for killing helminth effect
US11981645B1 (en) N′-(2-naphthoyloxy)-2-(benzo[d]oxazol-2-yl)acetimidamide as antimicrobial compound
CN107737338A (en) A kind of preparation for improving sensibility of bacteria on antibiotic

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20170426