CN101584657A - Tilmicosin solution and preparation method thereof - Google Patents
Tilmicosin solution and preparation method thereof Download PDFInfo
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- CN101584657A CN101584657A CNA2009100543666A CN200910054366A CN101584657A CN 101584657 A CN101584657 A CN 101584657A CN A2009100543666 A CNA2009100543666 A CN A2009100543666A CN 200910054366 A CN200910054366 A CN 200910054366A CN 101584657 A CN101584657 A CN 101584657A
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Abstract
The invention relates to a tilmicosin solution, mainly comprising injection water, tilmicosin and sodium bisulfite; 100ml of injection water contains 7.5-20g of tilmicosin and 0.05-0.2g of sodium bisulfite. The invention further relates to a preparation method of the tilmicosin solution, comprising partially weighing the injection water, regulating pH value, adding the tilmicosin, then adding the sodium bisulfite, supplying the injection water, adding active carbon, decarbonization and filtration. The invention solves the problem that tilmicosin phosphate is required to prepare the tilmicosin solution in the prior art and makes up for the shortage of the prior art.
Description
Technical field
The present invention relates to a kind of tilmicosin solution and preparation method thereof.
Background technology
Porcine respiratory disease complex claims " multiple-factor porcine respiratory disease ", " pig plyability pneumonia ", " porcine respiratory MOI " again.This disease is the height contagious disease, can pass through the air bamboo telegraph, mainly through respiratory tract infection, and also can be by propagation such as Placenta Hominiss.This disease principal character is: clinical symptoms is different, and the course of disease is long, the course of treatment is long, must could control by drug combination.This disease is more in cold season morbidity, raises that sanitary condition is poor, colony house humidity, crowded and improper ventilation or the easiest initiation of parasitic disease.
The syndromic pathogenesis of porcine respiratory is quite complicated, is the compound disease of a kind of multiple-factor.Mainly influence each other and cause by the pessimal stimulation of constitutional cause of disease, Secondary cases or the concurrency cause of disease and environment, weather conditions.
1. the constitutional cause of disease
The syndromic constitutional cause of disease of porcine respiratory is comparatively complicated, and existing viral cause of disease also has bacterial pathogen, often is accompanying infection, and common cause of disease mainly contains:
Mycoplasma pneumoniae (MH).This cause of disease causes mycoplasmal pneumonia of swine, claims epidemic swine pneumonia again.Be the chronic respiratory tract disease of pig, the pig at different cultivars, age all can infect, and with suckling pigling and the easy infection of children pig in age, secondly is latter half of gestation and nursing sow especially, and adult pig is chronic or inapparent infection more.With cough, panting is feature.The primary disease mortality rate is not high, but infectious rate height, in a single day the pig farm is caught an illness and is difficult to thoroughly eliminate, also can make infected pigs's hypoevolutism, this sufferer pig is gone too far sooner or later, eats food or drive the continuous tens of times dry cough of bowing, asthma, the breathing of normal appearance of motion back and increases number, per minute can reach 50 times～90 times, even 100 times.Cut open and be both sides pathological changes symmetry in the inspection lung, obvious with the normal lung tissue boundary; that diseased region is bois de rose or lark; that hardness increases; that outward appearance is like liver; as because bronchus cilium system is mainly destroyed and benumbed to mycoplasma, to cause the disease pig can not effectively stop the source of the gas venereal bacteria to enter respiratory tract and pulmonary, very easily bring out other bacterial respiratory tract diseases.
Porcine reproductive and respiratory syndrome (PRSV).This cause of disease causes pig breeding dysfunction and respiratory syndrome, is commonly called as " pig blue-ear disease ".This disease transmission approach is many, propagates rapidly, often can propagate into most pig farms or area in the short time.The infectiousness of sick pig is strong, as long as very low dosage, via intranasal application or injecting pathway infect the pig upper respiratory tract and pharyngeally can cause infection, in case infect, virus can be stored in urine, saliva and the seminal fluid.
Sow: occur inappetence, dyspnea, heating, drowsiness, spiritual depressed repeatedly.The normal respiratory symptom that shows is miscarried, premature labor, stillbirth, mummy tire then.Sick pig milk reduces the recurrence of estrus.
Boar: mainly show as inappetence, heating, drowsiness, spiritual depressed, often show respiratory symptom.Libido reduces, and semen quality descends, oligospermia, and vigor is low.
The suckling pigling: eyes swelling is outstanding, conjunctivitis.Extremity represent " eight " word foot more, and dehydration is had bad physiques, and mouth breathing, is asthma sample respiratory disorder, and rhinorrhea has bleeding tendency.
Pigling and young pig: symptom is relatively gentleer, symptoms of respiratory disease, dyspnea, cough, pneumonia etc. only occur.
Because this virus mainly encroaches on and destroy pulmonary macrophage and monokaryon lymph-node cell, thereby make disease pig immunologic function degression and immunosuppressant, the resistance of other cause of diseases is weakened, secondary other diseases very easily, and suppress the immunizing potency of other vaccines.
Porcine contagious pleuropneumonia Actinobacillus (APP).This bacterium is the polymorphic little coccobacillus.This bacterium has 12 serotypes, and the strongest with 1 type and 5 type pathogenicities, this Actinobacillus resistance to external world is not strong, is easily killed by general disinfectant.Mainly infect by respiratory tract, acute case body temperature can rise to more than 42 ℃, and spirit is depressed, and rapid breathing flows out foam sample secretions from muzzle, and anti-mistake person's body temperature is not high, is intermittent cough, growth retardation.Pathological changes is more common in pulmonary, mostly is both sides property, and pathological changes portion is kermesinus, and boundary is clear, and hardness increases, and tangent plane is like liver, and a matter is full of color gel-shaped liquid.
Other constitutional cause of diseases: the constitutional cause of disease that causes porcine respiratory disease complex is except above-mentioned several cause of diseases, also have swine influenza virus (sIV), PRCV (Porcine Respiratory Coronavirus) (PRLV), Pseudorabies virus (PRV) etc., these constitutional cause of diseases can singlely be caused a disease, and also can fall ill with other pathogen infections.
2. Secondary cases cause of disease
After pig had infected the constitutional cause of disease, because body constitution descends, immune function was suppressed, and causes immunity degradation, and the ability of opposing cause of disease is suppressed and secondary, and concurrent various diseases has increased the weight of the order of severity of disease.Modal secondary cause of disease is as follows:
Pasteurella multocida (PM).This germ swine pasteurellosis claims pig lung plague again.The pigling easy infection, 1 day～5 days incubation period.Generally be divided into acute, subacute and chronic clinically.Acute general title " sore throat with dysphagia ", sudden onset, dead rapidly; The course of disease is long slightly, condition of illness significantly can show fervescence, useless exhausted, the asthenia universalis of appetite, do not rise or dysphoria, dyspnea, palpitating speed with crouching.Subacute type, spastic dry cough, dyspnea, nose stream viscous fluid just take place in fervescence, are mixed with blood sometimes, after become cough caused by pathogenic damp, sense pain when coughing, the palpation chest has violent pain.Chronic type has persistence cough and dyspnea sometimes, and nose flows a little vicidity secretions.
Other Secondary cases cause of diseases.Cause porcine respiratory disease complex Secondary cases cause of disease except above-mentioned cause of disease, also have the relevant cause of diseases that cause respiratory symptom such as Streptococcus suis (SS), the secondary haemophilus (HP) of pig, bronchus deteriorated blood bordetella bacilli (BB), mycoplasma hyorhinis (MHR), toxoplasma, Eperythrozoon, swine fever virus and ascariasis.
3. bad weather, environmental condition and irrational feeding and management
Former of causing except pathogenic microorganism of the respiratory syndrome disease of pig and the secondary disease, also closely related with bad weather, environmental condition and irrational feeding and management.
The variation of temperature amplitude is excessive, and day and night temperature is big, winter warming measure imperfection, summer, ventilation condition was poor, thereby made respiratory tract stimulation sensitivity to external world, and brought out respiratory tract disease.
Humidity is too high or too low, has changed the weather conditions in the colony house, causes pig body stress, and the breeding for cause of disease simultaneously provides suitable condition.
Stocking density is excessive, and the layout of a page without columns is too many with the house swinery, provides convenience to transmission of pathogen, has strengthened the infection probability of respiratory tract disease.
Swinery is flowed frequent, and the swinery source is complicated, differs too big, the swinery flow direction of mistake with group pig age in days.
Ventilated bad in the house, harmful gas and dust exceed standard, and stimulate respiratory mucosa inflammation to occur, have reduced the protective effect of respiratory mucosa, for the invasion of cause of disease " is opened the floodgates wide ".
Feeding and management personnel's faulty operation, the string hurdle does not have fixed operation sequence from piglets to big pig, becomes the disseminator to a certain extent.
The swinery hygienic measures is incapable, and anthelminthic effect is not good, and unsound and pig malnutrition of the immune measure of sterilizing etc. all can quicken the generation of prdc.
The epidemic prevention system is unsound, the anti-epidemic measure imperfection, and vaccine program is not in place, for some cause of diseases that cause respiratory tract disease provide propagation conditions.
Clinical symptoms with cut open the inspection pathological changes
The clinical symptoms of porcine respiratory disease complex with cut open the inspection pathological changes show different because of pathogenic factor is different, its classical symptom has: dyspnea, frequency are accelerated, cough, are breathed, sneeze and ventral breathing, loss of appetite or useless exhausted, by hair is thick disorderly, efficiency of feed utilization is low, poor growth, size are uneven, some becomes " cad pig ".Cut open inspection pathological changes performance: pneumonia, pleuritis, pericarditis, pulmonary's substantial variations, hemorrhage, adhesion and edema; Hilus pulumonis and inguinal lymph nodes enlargement; The sick pig personal comments of part catch an illness that the different also ill initial heats of substance, fervescence, spirit are depressed, a conjunctiva inflammation, discharge of eye increase, watery nasal discharge or asoscope drying; Ear, the inferior place of abdomen skin cyanosis, eqpidemic disease later stage diarrhoea, depleted death of sick pig or anti-mistake become cad pig.
Comprehensive preventive health measures
Because the cause of disease complexity of porcine respiratory disease, the symptom performance differs, and brings inconvenience therefore for diagnosis and treatment.Should adhere to putting prevention first, prevent and treat bonded measure, the prevention and treatment method of taking veterinary to combine with Animal Science is controlled; If the sick pig or the epidemic-stricken area of having infected, can adopt immunity inoculation, antibiotic therapy and in conjunction with good feeding and management control Secondary cases, primary disease.
1. improve feeding and management condition
Carry out closed production, adhere to principle, prevent to introduce the inapparent infection pig from numerous autotrophy.Each production link adopts the mode of production of " all-in and all-out ", and each unit, every batch of pig all require size to differ not too big, and it is identical to originate, and carries out the interval work between every batch of pig.Strengthen sterilization, isolate, prevent exogenous cause of disease intrusion.Improve microclimate environment,, strengthen ventilatedly, keep air fresh as suitable reduction stocking density.Carry out personnel's management, the proper operation program, correct pig only flows to, and checks erroneous ideas at the outset.Carry out pig house preventing heatstroke in summer, warming work in winter, nutrition and the control pig farm scale and the breeding stock etc. of reasonable science are provided.Preferably make perfect bio-safety plan according to the practical situation on own pig farm, and strict the execution, anti-cause of disease is outside the pig farm.
2. carry out the inoculation work of all kinds of vaccines
Conscientiously carry out the common disease immunity, set up rational immune programme for children, control the generation of principal disease well.With good conditionsi can a situation arises formulates corresponding immune programme for children (seeing Table lattice) according to the various eqpidemic diseases in concrete pig farm, recommend immune programme for children, can select as the case may be to use.
3. prophylactic, in multiple season of prdc or epidemic-stricken area as yet not the swinery of morbidity shift to an earlier date medication and prevent
Cause that the syndromic reason of porcine respiratory is a lot, many times all be mixed infection in practice, therefore to breaking out the syndromic sick pig of porcine respiratory except that carrying out disinfectant anti-epidemic work, should take active measure to come spreading of control disease immediately, to reduce unnecessary loss.
Summary of the invention
The purpose of this invention is to provide a kind of tilmicosin solution, mainly comprise water for injection, tilmicosin and sodium sulfite, contain 7.5～20g tilmicosin and 0.05～0.2g sodium sulfite in every 100ml water for injection.Another object of the present invention provides a kind of preparation method of tilmicosin solution, comprises that part is measured water for injection, regulates the ph value, adds tilmicosin, adds sodium bisulfate again, supplies water for injection, added activated carbon, decarburization and filtration step.The invention solves prior art and need adopt the phosphoric acid tilmicosin to prepare the problem of tilmicosin solution, remedied the deficiencies in the prior art.
A kind of tilmicosin solution of the present invention mainly comprises water for injection, tilmicosin and sodium sulfite, contains 7.5～20g tilmicosin and 0.05～0.2g sodium sulfite in every 100ml water for injection.
As optimized technical scheme:
Aforesaid a kind of tilmicosin solution, wherein, described tilmicosin solution also comprises phosphoric acid, contains 2～5g phosphoric acid in every 100ml water for injection.
The preparation method that a kind of tilmicosin solution also is provided of the present invention may further comprise the steps:
(1) water for injection of the volume total amount 60～70% of the adding tilmicosin solution of preparing in preparing tank stirs, and is strong phosphoric acid adjusting ph value to 3.7～4.3 of 5%～100% with concentration;
(2) add tilmicosin, addition by the volume total of the required water for injection of the tilmicosin solution of preparing, add 7.5～20g tilmicosin in every 100ml water for injection, slowly also gradation adding of the adding of tilmicosin, added 20% of blanking total amount in per ten minutes, divide to add for 5 times, can make the abundant combination of tilmicosin and phosphoric acid like this;
(3) all to add back reuse concentration be that 5%～100% strong phosphoric acid is regulated the ph value to 3.5-4.0 to tilmicosin, makes material all molten clear;
(4) add sodium sulfite again, addition adds 0.05～0.2g sodium sulfite by the volume total of the required water for injection of institute's tilmicosin solution of preparing in every 100ml water for injection, and stirring makes dissolving, is warmed to 50～60 ℃;
(5) adding the injection water makes total amount reach institute to join the tilmicosin solution cumulative volume, press the every 100ml of tilmicosin solution cumulative volume and add 0.1g injection activated carbon, heat 50～60 ℃, decarburization 20～40 minutes under stirring, by membrane filtration, obtain required tilmicosin solution after filtration then.
The preparation method of aforesaid a kind of tilmicosin solution wherein, can be heated to 40～50 ℃ after described (3) the step joint ph value, makes material all molten clear.
The preparation method of aforesaid a kind of tilmicosin solution, wherein, described filter membrane adopts 0.45 micron.
The invention has the beneficial effects as follows:
A kind of tilmicosin solution of the present invention and preparation method thereof directly adopts tilmicosin rather than phosphoric acid tilmicosin to prepare tilmicosin solution, has significantly reduced production cost.
The specific embodiment
Below in conjunction with the specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
A kind of tilmicosin solution of the present invention mainly comprises water for injection, tilmicosin and sodium sulfite, contains 7.5～20g tilmicosin and 0.05～0.2g sodium sulfite in every 100ml water for injection.
Wherein, described tilmicosin solution also comprises phosphoric acid, contains 2～5g phosphoric acid in every 100ml water for injection.
The preparation method that a kind of tilmicosin solution also is provided of the present invention may further comprise the steps:
(1) water for injection of the volume total amount 60～70% of the adding tilmicosin solution of preparing in preparing tank stirs, and is strong phosphoric acid adjusting ph value to 3.7～4.3 of 5%～100% with concentration;
(2) add tilmicosin, addition by the volume total of the required water for injection of the tilmicosin solution of preparing, add 7.5～20g tilmicosin in every 100ml water for injection, slowly also gradation adding of the adding of tilmicosin, added 20% of blanking total amount in per ten minutes, divide to add for 5 times, can make the abundant combination of tilmicosin and phosphoric acid like this;
(3) all to add back reuse concentration be that 5%～100% strong phosphoric acid is regulated the ph value to 3.5-4.0 to tilmicosin, makes material all molten clear;
(4) add sodium sulfite again, addition adds 0.05～0.2g sodium sulfite by the volume total of the required water for injection of institute's tilmicosin solution of preparing in every 100ml water for injection, and stirring makes dissolving, is warmed to 50～60 ℃;
(5) adding the injection water makes total amount reach institute to join the tilmicosin solution cumulative volume, press the every 100ml of tilmicosin solution cumulative volume and add 0.1g injection activated carbon, heat 50～60 ℃, decarburization 20～40 minutes under stirring, by membrane filtration, obtain required tilmicosin solution after filtration then.
Wherein, can heat to 40～50 ℃ after described (3) the step joint ph value, make material all molten clear.Described filter membrane adopts 0.45 micron.
Pharmacokinetics: a kind of tilmicosin solution of the present invention is for oral administration and the subcutaneous injection absorption is fast.Apparent volume of distribution is big, the drug level height in the lung tissue.Have the favorable tissue penetration power, can enter breast from blood rapidly and fully, the Ruzhong drug level is higher, the length of holding time, and the Ruzhong half-life reaches 1--2 days.
Pharmacological action: gram positive bacteria, some gram negative bacteria, mycoplasma, spirillum etc. are all had inhibitory action; Pleuropneumonia actinomycetes, pasteurellosis bacillus had the antibacterial activity stronger than tylosin.
Tilmicosin (Tilmicosin) is a kind of newer for the special-purpose antibiotic of the semisynthetic Macrolide poultry of tylosin, and the eighties is succeeded in developing by Britain Elanco Animal Health Care Products Corporation.Because its special antibacterial activity and characteristics of pharmacokinetics, the clinical control that is used for animal infectious diseases such as cattle, goat, sheep, milch cow, pig, chicken that gone through of this medicine, particularly livestock and birds respiratory disease reaches the treatment of lactogenic mammitis of animal as domestic animal Actinobacillus property pleuropneumonia, Bacillus pasteurii disease and gallisepticum chicken disease etc.For understanding tilmicosin and application thereof, now the research about aspects such as its antibacterial activity, pharmacokinetics, pharmacodynamics, toxicology and clinical practices is summarized as follows respectively.
1 antibacterial activity
Tilmicosin has with the similar broad spectrum antibiotic activity of tylosin, gram positive bacteria and some gram negative bacteria, Mycoplasma, spirillum etc. all there are inhibitory action, Actinobacillus pleuropneumoniae, pasteurellosis bacillus and Mycoplasma are had the antibacterial activity stronger than tylosin.Reports such as Inamoto, tilmicosin (TMS), chlortetracycline (CTC), thiamphenicol (TP) and tylosin (TS) to Japan 1985～1989 in the period of from the antibacterial actions of isolated 61 strain pasteurella multocida of hyopneumoniae damaging part and 35 strain Actinobacillus pleuropneumoniaes, most of bacterial strains are to TMS, CTC, TP sensitivity.CTC and TP have inhibitory action to 51 strains (83.6%) and 46 strains (75.4%) pasteurella multocida respectively when 3.13 μ g/ml and 0.78 μ g/ml.TS is lower to the antibacterial activity of almost all strains, MIC 〉=6.25 μ g/ml.TMS is to MIC 〉=1.56 μ g/ml of 23 strains (37.7%) pasteurella multocida, but when 3.13 μ g/ml, TP and TMS can suppress 32 strains (91.4%) and 33 strains (94.3%) Actinobacillus respectively, as seen as same Macrocyclolactone lactone kind medicine, tylosin to the antibacterial activities of two kinds of antibacterials all not as good as tilmicosin.Salmon SA etc. uses the 515 strain pathogenic bacterium that are separated to from the U.S., Canada that the sensitivity of 9 kinds of medicines such as ceftiofur, enrofloxacin, erythromycin, sulfadimidine, spectinomycin, lincomycin, sulfadiazine/TMP, ampicillin and tilmicosin is measured.Found that what antibacterial action was the strongest is enrofloxacin and ceftiofur, tilmicosin is medium to pasteurellosis bacillus and Actinobacillus pleuropneumoniae activity.Tilmicosin shows stronger antibacterial activity in vitro to the chicken Mycoplasma.Jordan etc. have reported tilmicosin and the tylosin external MIC value to poultry 6 strain mycoplasma gallisepticums and 3 strain synovial fluid Mycoplasmas.Tilmicosin is respectively the MIC value of 6 strain mycoplasma gallisepticums:＜0.0125,0.0025,0.0025, and＞12.5,0.004,0.1,0.0125,0.006 and 0.025 μ g/ml; The MIC value of tylosin then is respectively:＜0.0125,0.02,0.02,3.2,0.016,0.8,0.0125,0.025 and 0.025 μ g/ml.Application tilmicosins such as Ziv are to carrying out MIC-90 mensuration from the isolating 112 strain staphylococcus aureuses of mammitis of cow and other pathogenic bacterium.Tilmicosin is all very sensitive to mastitis staphylococcus aureus and streptococcus as a result, wherein to micrococcus scarlatinae activity the strongest (MIC-90 is 0.04 μ g/ml).Tilmicosin can suppress other Gram-positive mastitis pathogenic bacterium of 90.8% less than .3.12 μ g/ml the time.
2 pharmacokinetic studies have been carried out the tilmicosin pharmacokinetic study animals such as milch cow, milk goat, sheep, cattle, pigs, but do not see the pharmacokinetics report of poultry.The tilmicosin intravital main characteristics of pharmacokinetics of poultry of being in is: for oral administration and subcutaneous injection absorbs fast, the elimination half-life is longer in the blood, has the favorable tissue penetration power, can fully enter breast rapidly and from blood, milk Chinese medicine concentration height, the length of holding time is eliminated the half-life and is reached 1～2d in the milk.In addition, tilmicosin is at lung tissue Chinese medicine concentration height, and apparent volume of distribution is big in the body.Ziv etc. have reported that tilmicosin is in the intravital characteristics of pharmacokinetics of milch cow.Blood drug level that the performance of quiet notes (10mg/kg) back is lower and bigger apparent volume of distribution (＞2.0l/kg), eliminating the half-life in the blood is 46.4～72.8min, during administration 30min, milk and blood Chinese medicine concentration C max ratio are 30.1～10.1, and eliminating the half-life in the milk is 22.6h.The average bioavailability of subcutaneous injection (10mg/kg) is 22%, and eliminating the half-life in the blood is 4.18h, and the milk drug level is higher than nearly 50 times of blood drug level in the administration 30min, and eliminating the half-life in the milk is 21.06h.As seen the common characteristics of pharmacokinetics after milch cow subcutaneous injection and the quiet notes administration is that medicine enters in the milk rapidly, and the drug level height, and the length of holding time is eliminated slowly.Thomson etc. have measured the administration of tilmicosin spice in the intravital concentration of pig.Be respectively 0.73～1.43 μ g/ml and 1.11～2.59 μ g/ml by lung tissue Chinese medicine concentration behind 200mg/kg, 400mg/kg feedstuff (be equivalent to 1097,21.34mg/ (kgd)) the successive administration 14d, all be lower than the MIC value (〉=3.0 μ g/ml) of the tilmicosin of report such as Moore hyopneumoniae pathogen (Actinobacillus pleuropneumoniae APP and pasteurella multocida PM).But clinically, some countries of US and European have used the hyopneumoniae that 200～400mg/kg spice administration prevention causes by APP and PM and have obtained good result.For inquiring into reason, this research is by in vitro tests, using the elementary pulmonary alveolar macrophage of pig hatches in the culture matrix that contains tilmicosin 10 μ g/ml and 20 μ g/ml, mensuration enters intracellular drug level, the result is similar with pulmonis Bovis seu Bubali bubble macrophage, the elementary pulmonary alveolar macrophage of pig has very strong drug accumulation ability, and prolongs concentration in time and obviously raise.Scorneanx etc. also confirm that it is to be positioned in the lysosome that the subcellular fraction of about 70%～80% tilmicosin distributes.This shows to be accumulated as clinically to the height of tilmicosin by the domestic animal pulmonary alveolar macrophage effective control of pneumonia provides the foundation that promptly blood and lung tissue Chinese medicine level are lower than the MIC value of pathogenic bacterium.
3 pharmacodynamicss and clinical application research
Tilmicosin is mainly used in control domestic animal pneumonia (infection such as Actinobacillus pleuropneumoniae, pasteurellosis bacillus, Mycoplasma), poultry mycoplasma and lactogenic mammitis of animal etc. clinically.
3.1 the cattle tilmicosin by 10,20, the injection of 30mg/kg single dose subcutaneous, the calf pneumonia of treatment natural infection pasteurellosis bacillus, all can significantly reduce body temperature (in the 24h), alleviate clinical symptoms, lung tissue lesion degree, reduce pasteurellosis bacillus quantity and mortality rate in the lung.Tilmicosin (10mg/kg) and sharp proceomycin (5mg/kg lincomycin and 10mg/kg spectinomycin mixture) treatment natural infection pneumonia, the single dose tilmicosin obviously is being better than sharp proceomycin aspect elimination symptom and the appetite stimulator, by pulmonary's pathogen isolation and evaluation, both are to the slip no significant difference of pasteurellosis bacillus and Mycoplasma.Long-acting terramycin (20mg/kg) and tilmicosin (10mg/kg) are to the preventive effect of 1806 beef cattle pneumonia, and two medicines all can significantly reduce the M ﹠ M of pneumonia and other multiple disease.Tilmicosin obviously is being better than long-acting terramycin aspect weightening finish, the relief of symptoms.
3.2 pig
Tilmicosin generally is prevention and the treatment of carrying out hyopneumoniae by the spice administration.Tilmicosin prevents pig natural infection pneumonia and compares with oxytetracycline (400mg/kg spice), confirm that tilmicosin is by 200～400mg/kg spice, during logotype 15d the pneumonia sickness rate and the order of severity thereof there are remarkable reduction, can prevent bacterial pneumonia (as Actinobacillus or/and pasteurellosis bacillus) preferably.
3.3 poultry
Because tilmicosin has stronger antibacterial activity to the poultry Mycoplasma, has been used to treat the poultry mycoplasma, and has obtained effect preferably.Tilmicosin with 50,100,200, the 300mg/l administration of drinking water, experimental mycoplasma galliseplicum disease is had good preventing and therapeutic effect.At tilmicosin and tylosin treatment mycoplasma gallisepticum
Sick curative effect comparative result shows that tilmicosin (0.25g/l) is close with tylosin (0.5g/l) curative effect.
3.4 the lactogenic animal is used the curative effect of tilmicosin and ceftiofur to the milk cow in lactation period staphylococcus aureus mastitis.Behind treatment 28d, tilmicosin breast perfusion (300mg, logotype 6 times) cure rate is the highest only reaches 91% (referring in the 28d repeatedly sampling all separates less than staphylococcus aureus is assessed as healing), but tilmicosin subcutaneous injection (3000mg/d, logotype 3d) with ceftiofur (breast perfusion 200mg, logotype 6 times; Intramuscular injection 500mg, logotype 3d) all can significantly reduce somatic cell (SCC) quantity of one of bacterial number and mastitis index in the newborn sample.
3.5 clinical practice
When on the veterinary clinic tilmicosin being used for disease such as prevention and treatment poultry pneumonia and mastitis, subcutaneous injection 10～20mg/kg once can obtain good efficacy.Can take the mode of 200～400mg/kg spice administration 15d when prevention and treatment swine mycoplasma pneumonia, poultry often by 100～200mg/l drinking-water logotype 5d, can prevent and treat mycoplasma, but be not used in laying hen.The definite curative effect of tilmicosin treatment mastitis is still to be tested, but perfusion 300mg/ time in subcutaneous injection 10mg/kg or the breast in milch cow does the breast phase, control action is played in growth, the breeding of mitigation symptoms and inhibition pathogenic bacterium preferably.
Claims (5)
1. tilmicosin solution, it is characterized in that: tilmicosin solution mainly comprises water for injection, tilmicosin and sodium sulfite, contains 7.5～20g tilmicosin and 0.05～0.2g sodium sulfite in every 100ml water for injection.
2. a kind of tilmicosin solution as claimed in claim 1 is characterized in that described tilmicosin solution also comprises phosphoric acid, contains 2～5g phosphoric acid in every 100ml water for injection.
3. the preparation method of a tilmicosin solution is characterized in that, may further comprise the steps:
(1) water for injection of the volume total amount 60～70% of the adding tilmicosin solution of preparing in preparing tank stirs, and is strong phosphoric acid adjusting ph value to 3.7～4.3 of 5%～100% with concentration;
(2) add tilmicosin, addition by the volume total of the required water for injection of the tilmicosin solution of preparing, add 7.5～20g tilmicosin in every 100ml water for injection;
(3) all to add back reuse concentration be that 5%～100% strong phosphoric acid is regulated the ph value to 3.5-4.0 to tilmicosin, makes material all molten clear;
(4) add sodium sulfite again, addition adds 0.05～0.2g sodium sulfite by the volume total of the required water for injection of institute's tilmicosin solution of preparing in every 100ml water for injection, and stirring makes dissolving, is warmed to 50～60 ℃;
(5) adding the injection water makes total amount reach institute to join the tilmicosin solution cumulative volume, press the every 100ml of tilmicosin solution cumulative volume and add 0.1g injection activated carbon, heat 50～60 ℃, decarburization 20～40 minutes under stirring, by membrane filtration, obtain required tilmicosin solution after filtration then.
4. the preparation method of a kind of tilmicosin solution as claimed in claim 3 is characterized in that, can heat to 40～50 ℃ after described (3) the step joint ph value, makes material all molten clear.
5. the preparation method of a kind of tilmicosin solution as claimed in claim 3 is characterized in that, described filter membrane adopts 0.45 micron.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102657607A (en) * | 2012-05-25 | 2012-09-12 | 鼎正动物药业（天津）有限公司 | Tilmicosin stabilizing agent and preparation method thereof |
| CN103301057A (en) * | 2013-06-09 | 2013-09-18 | 江西英特科胜动保科技有限公司 | Tilmicosin injection capable of improving low-temperature freezing resistance and preparation method of tilmicosin injection |
| CN103462884A (en) * | 2013-08-21 | 2013-12-25 | 挑战（天津）动物药业有限公司 | Gamithromycin injection and preparation method thereof |
| CN104473958A (en) * | 2014-12-15 | 2015-04-01 | 洛阳瑞华动物保健品有限公司 | Compound premix and preparation method and application thereof |
| CN104958313A (en) * | 2015-06-17 | 2015-10-07 | 侯强红 | Tilmicosin and ceftiofur injection and preparing equipment and process |
| CN116172952A (en) * | 2023-04-21 | 2023-05-30 | 浙江大学 | Tilmicosin xylitol compound injection and preparation method thereof |
-
2009
- 2009-07-03 CN CNA2009100543666A patent/CN101584657A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102657607A (en) * | 2012-05-25 | 2012-09-12 | 鼎正动物药业（天津）有限公司 | Tilmicosin stabilizing agent and preparation method thereof |
| CN103301057A (en) * | 2013-06-09 | 2013-09-18 | 江西英特科胜动保科技有限公司 | Tilmicosin injection capable of improving low-temperature freezing resistance and preparation method of tilmicosin injection |
| CN103462884A (en) * | 2013-08-21 | 2013-12-25 | 挑战（天津）动物药业有限公司 | Gamithromycin injection and preparation method thereof |
| CN104473958A (en) * | 2014-12-15 | 2015-04-01 | 洛阳瑞华动物保健品有限公司 | Compound premix and preparation method and application thereof |
| CN104958313A (en) * | 2015-06-17 | 2015-10-07 | 侯强红 | Tilmicosin and ceftiofur injection and preparing equipment and process |
| CN104958313B (en) * | 2015-06-17 | 2018-02-02 | 侯强红 | A kind of Tilmicosin and Cefliofur injection and process equipment and technique |
| CN116172952A (en) * | 2023-04-21 | 2023-05-30 | 浙江大学 | Tilmicosin xylitol compound injection and preparation method thereof |
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