CN101433531B - Use of substance formaldehyde in preparing medicament for coccidiosis of animal - Google Patents
Use of substance formaldehyde in preparing medicament for coccidiosis of animal Download PDFInfo
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Abstract
The invention relates to novel application of preventing and treating mammalian coccidiosis by of the prepared formaldehyde in the field of animal drugs. The invention provides and proves that application of the formaldehyde has certain effects, advantages and the like in preventing and treating the mammalian coccidiosis, thereby further providing a medicine prepared by the formaldehyde and used for preventing and treating the mammalian coccidiosis.
Description
[affiliated technical field]
The present invention relates to the new purposes of a kind of material in the preparation animal drug.Relate in particular to the purposes of formaldehyde in preparation control medicament for coccidiosis of animal.
[background technology]
One, about animal's coccidiosis and the control medicine prior art:
1. coccidiosis is to raise a kind of common disease that is found in multiple animal in the Production of Livestock and Poultry, and clinical manifestation is mainly with hemorrhagic enteritis, dysentery, and young stock fowl (chickling etc.) sickness rate height and mortality rate height are feature.Coccidiosis extensively parasitizes in multiple poultry, domestic animal, wild animal and the aquatic animal digestive tract, and its high incidence can bring serious economy loss to aquaculture.According to incompletely statistics, in poultry husbandry, the chicken coccidiosis sickness rate is 50%-70%, and mortality rate is 20%-30%, and mortality rate can reach 80% when occurred frequently.15%-20% in the piglet diarrhea disease is that coccidiosis causes, the Epidemiological study of European countries shows, the whole world has the pig farm of 83%-100% that the pig coccidium infection is arranged approximately, endogenous cause of ill coccidium infection economic loss every year of being caused is all up to multi-billion dollar (Wang Fang etc., Henan animal and veterinary-2007:28 (06S)-22-23) in the world.
2. coccidiosis has a lot of kinds, without any a kind of medicine the coccidiosis of all kinds is all had desirable curative effect, " the Drug resistance coccidiosis develops immunity to drugs behind the contact medicine ..., coccidiosis has Drug resistance widely." ((U.S.) B.W. Ka Ernike chief editor, " disease of poultry " the 9th edition, publishing house of Beijing Agricultural University, 694 pages)
3. following situation is known altogether: for fear of drug residue to the harm of human health and the Drug resistance problem of coccidiosis, now developed the vaccine of several prevention coccidiosiss, but every kind of vaccine just has specificity at the prevention of certain coccidiosis, and to preventing other kind coccidiosis invalid.
Two, relate to the practicality problem prior art that substance formaldehyde is used as coccidiostat;
1. " developed 8% formaldehyde-alcoholic solution, 11% formalin-promethazine solution abroad, its ten times of dilutions have promptly been lost zest ": " paraformaldehyde loses the zest of formaldehyde substantially." (Chai Jiaqian etc., practical fowl disease prophylactic, the 1st edition, Beijing: publishing house of University of Electronic Science and Technology, 1994:123).
2. the famous chemist king of China reforms in its monograph " formaldehyde discharges and detects " (Chemical Industry Press, in March, 2003 front page " formaldehyde is to the harm of health " one joint) discusses in: " formaldehyde shows as stimulation to mucosa to the main harm of health ", " it is very fast to enter the intravital formaldehyde metabolism of animal; be oxidized to formic acid immediately, then is oxidized to CO very soon
2, to breathe out from pulmonary, part formic acid is discharged from urine, so behind the humans and animals suction formaldehyde, concentration of formaldehyde is not seen rising in the blood." " with the external testing result of various mammals, proof formaldehyde has the effect of bringing out the mammalian cell gene mutation, and DNA there is damaging action, but the result of the test of whole animal is opposite, its main cause may be formaldehyde metabolism is fast in vivo, except that directly the contact formaldehyde organ (as nose and organ), away from the tissue of contact organ, seldom directly accept the effect of formaldehyde.”
3. formaldehyde is known altogether as animal intestines and stomach system ferment agent (seeing " Chinese veterinary drug allusion quotation " (version in 2005) " formalin " joint) and feed additive.
4. two patents (patent No. is respectively " ZL 200410044354.2 " and " ZL 200410044353.8 ") that relate to formaldehyde new purposes in the preparation animal drug that the applicant declared in 2004 successively were authorized in the current year.
[summary of the invention]
Substance formaldehyde involved in the present invention comprises: all contain the chemical compound of formaldehyde material and the formaldehyde material in the compositions formaldehyde, paraformaldehyde, formalin and other.
The present invention is based on this principle proposition: after activated coccidiosis Sporangium is taken in the digestive tract by host animal, need under chymase and bile effect, to slough Sporangium and enter and just can make the animal morbidity in the histiocyte such as intestinal, and trace (＞0.5 ‰) thus formaldehyde can suppress or destroy the effect of chymase to be made it slough Sporangium and enters histiocyte, therefore can avoid coccidium infection effectively or/and continue to damage animal body.
Substance formaldehyde involved in the present invention is used to prevent and treat animal's coccidiosis and has good result, therefore the medicament preparation that can be used for preventing and treating animal's coccidiosis.
The substance formaldehyde that the present invention relates to can be separately in purposes involved in the present invention as medicine, also can and other medicine make compound preparation; Can prepare veterinary clinic and use medicine, also can prepare animal feed additive.Its dosing way is digestive tract administration (comprising batch mixing).
The problem that may relate to practicality of the present invention about the formaldehyde material during as the purposes that the present invention relates to the issuable toxicity, side effect of animal and relevant food hygiene and environmental protection etc.:
Formaldehyde is the veterinary drug of national veterinary drug allusion quotation record, and the present invention has just increased new purposes for it.Because formaldehyde is when being used for the treatment of animal intestines and stomach system ferment, its route of administration also is a digestive tract, that is to say just differently with its disease preventing and treating purposes, and other is as indistinctions such as using method, route of administration and dosages.Therefore when implementing purposes of the present invention is that the oral formaldehyde of animal has practicality to the stimulation of each organ-tissue of digestive tract of animal and the effect of normal stool process.
The aforementioned inventor was authorized in the current year relates in two patents " description " of formaldehyde new purposes in the preparation animal drug, has all done more statement with regard to formaldehyde respectively in the aspect problems such as preparation practicality that are used to prepare the administration of animal via digestive tract.
[technique effect]
The present invention is implemented, for the control animal's coccidiosis has found that effect is certain, consumption is little, after effect is grown by force, coccidiosis to its can not develop immunity to drugs, the new drug of cheap, plurality of advantages such as worry that animal derived food does not have drug residue.
This invention is implemented on industrialization, will play huge impetus for the formaldehyde manufacturing industry, and will form a huge veterinary drug and related industry group thereof.
[specific embodiment]
(1) substance formaldehyde is used to prevent and treat animal's coccidiosis
Reference example 1: use paraformaldehyde and use the test of Robenidine and Amprolium batch mixing treatment chicken coccidiosis effect comparison
1.1 test period, place and tried chicken:
-22 days on the 13rd June in 2007; The strong chicken house of the southwestern street Wang Wen in eternally happy town, Zhaozhou County; 1800 Ai Weiyin broiler groups that infected coccidiosis of these chicken house 45 ages in days.
1.2 trial drug
1.2.1 tested medicine: paraformaldehyde, Beijing sharp chemicals of benefit has the product with company, analytical pure, lot number 20061207.Its formulation preparation method is: the paraformaldehyde sieve is gone than granule and powder, with sucrose (analytical pure) and Macrogol 4000 with 1: 3 mixed, 80 ℃ of fusions, (its packing technology is same as granule coating manufacturing process conventional method with this fused mass above-mentioned formaldehyde granule to be rolled into 10-20 order granule, the ratio of gains is 1: 9 after paraformaldehyde granule and the above-mentioned fusion), the room temperature cooling, this description described " formaldehyde preparation " promptly refers to this paraformaldehyde enwrapped granule.
1.2.2 control drug: commercially available robenidine hydrochloride powder (produce by the upright auxiliary chemicals company limited of Shanghai Xiang, pharmaceutical grade, lot number: 20060812, Robenidine content 〉=98%) and Amprolium (production of Chinese medicine biochemical industry company limited is closed in Wuhan, pharmaceutical grade, lot number: 20070123, Amprolium content 〉=99.2).
1.3 test method and process: large quantities of chickens generations were the disease of cardinal symptom with the hemafecia to this chicken house morning on the 12nd, were diagnosed as chicken coccidiosis through this chicken house veterinary clinic diagnosis and the check of animal and veterinary institute laboratory, Zhaozhou, Daqing.Went to a doctor at that time morning on the 13rd, and whole chicken house accumulative total has been fallen ill 388, sickness rate 21.54%, and dead 54 of accumulative total, mortality rate reaches 13.92%.
On-test at that time.With in the sick chicken 36 near dead eliminating, in other clinical symptoms significantly and in its feces, detect 200 of egg capsule, be divided into first group, second group, third group and fourth group at random.
The first group is used the paraformaldehyde preparation for formaldehyde therapeutic effect test administration group.Before feeding intake one hour, the ratio that accounts for feedstuff 200mg/kg in formaldehyde material actual content is with paraformaldehyde preparation and feedstuff mixing, and fed the same day.
Second group and third group are contrast administration group, and the second group is used, and the per kilogram feedstuff is sneaked into 60mg Robenidine spice, and third group is used Amprolium: the per kilogram feedstuff is sneaked into 60mg Amprolium spice.
The drug withdrawal after 3 days of first three groups successive administration was observed 7 days more jointly with other each group.
Curative effect determinate standard: after the administration, the variation of the aspects such as egg capsule in the spirit of observation every day, check and record chicken, appetite, hemafecia, the feces.Dead chicken is determined its cause of death by cuing open to pick up.
Curative effect determinate standard is:
1. cure: sick chicken medication after 3 days hemafecia stop, overall health of patients is good, feces does not have egg capsule and picks, viewing duration was no abnormal in back 7 days.
2. produce effects: medication after 3 days hemafecia stop, overall health of patients is good, has egg capsule to discharge in the feces.The 7 days viewing durations in back do not have disease symptom again and occur.
3. invalid: administration after three days hemafecia do not stop, but dead.
4. dead: duration of test death, through clinical symptoms record before death and cut open the inspection result and be defined as because of the coccidiosis chicken that causes death.
1.4 result of the test
Result of the test such as following table:
Table 1 paraformaldehyde is tested with using Robenidine and Amprolium batch mixing treatment chicken coccidiosis effect comparison
| Group | Chicken plumage number | Cure | Produce effects | Invalid | Dead | ||||
| Quantity | Ratio (%) | Quantity | Ratio (%) | Quantity | Ratio (%) | Quantity | Ratio (%) | ||
| The first and second the third fourths | ?50?50?50?50 | 50 31 34 - | 100 62 68 - | - 10 8 - | - 20 16 - | - 6 6 - | - 12 12 - | - 3 2 27 | - 6 4 54 |
Learn check by statistics, x2=169.4, p＜0.05, formaldehyde administration group therapeutic effect is better than other groups.Compare with the fourth group, formaldehyde treatment coccidiosis is effective.
Reference example 2: the test of using formaldehyde prevention rabbit coccidiosis to infect
2.1 test period, place and tried rabbit:
-11 days on the 2nd July in 2007; Zhaozhou, Daqing animal and veterinary institute; The livid purple blue rabbit of 300 20 ages in days of this self-fertile.
2.2 trial drug
2.2.1 tested medicine: environment disinfected formalin, Harbin City veterinary drug in the new year feed additive factory produces, and contains formaldehyde 36%, lot number: 20070110
2.2.2 control drug: the robenidine hydrochloride powder (produce by the upright auxiliary chemicals company limited of Shanghai Xiang, pharmaceutical grade, lot number: 20060812, Robenidine content 〉=98%) and Amprolium (production of Chinese medicine biochemical industry company limited is closed in Wuhan, pharmaceutical grade, lot number: 20070123, Amprolium content 〉=99.2).
2.3 test method and process:
2.3.1 test coccidian oocyst:
The Eimeria maxima egg capsule is provided by Zhaozhou, Daqing animal and veterinary institute parasitic disease laboratory, at young rabbit proliferation in vivo, obtains the fresh egg capsule that experimental infection is used with the saturated salt water law before the test, and counting is standby after the sporeization.
2.3.2 feedstuff and relevant issues are handled:
The disinfecting drug that uses such as test place, utensil can be killed coccidiosis and egg capsule thereof carries out strict sterilization, feeds utilized for from its self-produced corn of peasant family purchase, press soybean cake certainly, last two kinds of feedstuffs mix in self-control Leymus chinensis (Trin.) Tzvel. powder, except that duration of test adds trial drug, do not add any medicine and additive.
2.3.3 test grouping, infection and administration and relevant issues arrangement:
Above-mentioned 300 rabbits were carried out the empty stomach physical examination, weigh morning day on-test, with being in a good state of health of picking out, close 200 of there is no coccidium infection of body weight are divided into first, second, third at random, fourth, penta 5 groups, 40 every group.First, second, third, fourth, penta group respectively be infection to the formaldehyde group, infect to the Robenidine group, infect, infect not administration group and do not infect not administration group to the Amprolium group.Respectively organize rabbit after the grouping and be isolated in separately experiment place, raise, check that each organizes rabbit does not have mutual infection coccidiosis approach by the special messenger respectively.
Coccidium infection: except that penta group, other are respectively organized every rabbit and threw to 8 * 10 through the oral cavity in second day in the beginning administration
10Individual Eimeria maxima egg capsule.
The dosage and the method for each group of administration:
First group: get the above-mentioned formalin of 3ml (reality contains formaldehyde material 1.08 grams approximately), add 10 times of glycerol, add 5% G/W again, the formalin that contains formaldehyde 0.02% is in fact approximately freely drunk for rabbit as daily only drinking water to 5000ml.Calculate according to rabbit actual average amount of drinking water, every rabbit is on average taken in the about 0.1g of formaldehyde material every day.
The second group: the feedstuff of whole test phase, contain 50mg Robenidine mixing by per kilogram, supply to feed the rabbit free choice feeding as the only feedstuff of rabbit.Calculate according to rabbit feedstuff actual consumption amount, every rabbit is on average taken in the about 0.1g of Robenidine every day.
Third group: the feedstuff of whole test phase contains Amprolium 125mg mixing by per kilogram and supplies the rabbit free choice feeding as the only feedstuff of rabbit.Calculate according to rabbit feedstuff actual consumption amount, every rabbit is on average taken in the about 0.25g of Robenidine every day.
Five groups of rabbits of full entry test were checked the hemafecia phenomenon of feces every day and had or not egg capsule and record, until catching and killing from the 2nd day on-test.Inoculation the 9th day the survival rabbit is all slaughtered and cuts open inspection, check whole intestinal pathological changes.
2.4. result of the test:
Sickness rate hemafecia and/or intestinal occur with rabbit and the due dissection of coccidiosis occurs and be changed to standard, and both a person occurs and all count the morbidity rabbit.
The result of the test that table 2. uses formaldehyde prevention rabbit coccidiosis to infect
| Group | The rabbit number of elements | The morbidity number of elements | Sickness rate (%) |
| The first and second the third fourths | 40 40 40 40 | 0 3 2 17 | 0 7.5 5.0 42.5 |
| Penta | 40 | 0 | 0 |
X2=52.13, p＜0.05, using formaldehyde preparation prevention rabbit coccidiosis to infect as can be seen from the table is effectively, and more effective than using this sick traditional drug Robenidine and Amprolium of control.
Reference example 3: substance formaldehyde and diclazuril control chickling coccidiosis effect contrast test
On June 12nd, 2006, we carried out formaldehyde material and the effect test of preventing and treating coccidiosis conventional medicament " ball essence " (diclazuril) control broiler chicken artificial challenge coccidiosis under the cooperation of Zhaozhou, Daqing animal and veterinary institute animal parasitosis test chamber to June 20.
3.1 material and method
3.1.1 test chicken:
From incubating 400 of 15 age in days AA broiler chicken.
3.1.2 test and drugs compared:
Self-control paraformaldehyde preparation: see that per 100 kilograms of feedstuffs contained by formaldehyde material 20g consumption batch mixing when embodiment 1. used this preparation.
The ball essence restrains sharp pearl 0.5% with containing, and Ke Fa animal pharmaceutical factory of Northeast Agricultural University produces, lot number: 20050101 contain 20g ground according to per 100 kilograms of feedstuffs restrains sharp pearl consumption batch mixing.
3.2 test method and process
3.2.1 test grouping: above-mentioned young broiler is divided into each first, second of 100, third and four groups of fourths and respectively to each cohort body sum of weighing at random, the first group is formaldehyde material (paraformaldehyde preparation) test administration group, the second group is a diclazuril contrast administration group, third group for infecting not administration group, and Ding Zuwei does not infect not administration group.
3.2.2 infected insect species class and quantity: chicken Eimeria worm kind (providing), first, second and third group of every plumage of chicken oral 8 * 10 by Zhaozhou, Daqing animal and veterinary institute parasitic disease laboratory
10Individual sporinite egg capsule, the fourth group is not given.
3.2.3 medication: every group of medicine is by the even batch mixing of above-mentioned dose.Each group threw to mixing the medicine feedstuff for worm sporinite egg capsule in preceding 24 hours.Connect to give 7 days, first three groups (fingernail, second and third group) collected feces on the 6th day for polypide throwing, and the egg capsule numeration was weighed to cut open and killed the tissues observed pathological changes on the 7th day.
3.2.4 drug effect is judged index:
1. survival rate: survival chicken plumage is counted ÷ 100 (jungle fowl plumage number) * 100%.
2. the relative weight gain rate: do not give rate of body weight gain * 100% of worm sporinite egg capsule group respectively for the rate of body weight gain ÷ of worm sporinite egg capsule group.
3. hemafecia is kept the score: with reference to Morehouseh and Barron (1970) standard (Morehouse.N.F.and baron R.R.Experiment parasitology, 1970,28:29～25).
4. lesion score: press Johnson and Reid (1970) standard (Johnsan, J.and Reid W.H.Experiment parasitology, 1970,28:30～36.
5. pathological changes value: by field, angle clearing method [the clear prison in (day) field, angle is repaiied. Chen Yi, brightly translate chicken coccidiosis disease as mirror. Shanghai: the Shanghai scientific and technical literature .1983 of publishing house].
6. the egg capsule value is converted into the egg capsule value with the gram egg sac number of cecal content by the standard of angle Tian Qing.
7. anticoccidial index (ACI): according to Merck company formula (Anticoccidial index merck sharp and Dohme lab), ACI=(the relative weight gain rate+survival rate)-(pathological changes value+egg capsule value), ACI≤120 are invalid, ACI=120～160 are middle effect, ACI=160～180 are good, and ACI＞180 are outstanding.
3..3. result of the test:
Table 3. uses substance formaldehyde control chickling coccidiosis and conventional medicament examination contrast test
| Group | Chicken plumage number | Survival rate | The relative weight gain rate | Hemafecia is kept the score | The pathological changes value | The egg capsule value | ACI |
| (％) | (％) | (on average) | |||||
| The first and second the third fourths | ?100?100?100?100 | 100 91.3 73.0 100 | 98.9 92.1 46.4 100.0 | 0 1.5 4.1 - | 8 15 38.7 - | 3 11 45 - | 187.9 157.4 35.7 200.0 |
As can be seen from the above table: use the first group anticoccidial of formaldehyde material very effective, and obviously be better than the second group of using diclazuril; According to the computing formula of above-mentioned Merck ﹠ Co., Inc., the anticoccidial index of formaldehyde material is outstanding.Reference example 4: substance formaldehyde is treated calf coccidiosis effect contrast test with using sulfamethazine
On 7 days-August 16 August in 2007, we carry out the formaldehyde material and prevent and treat the effect test that beef cattle infects coccidiosis with control coccidiosis conventional medicament sulfamethazine under the cooperation of animal and veterinary institute animal experiment chamber, Zhaozhou, Daqing.
4.1 material and method
4.1.1 test cattle
42 2-3 monthly age calf generation hemafecia phenomenon in 541 finished cattles that Wan Bao township, Zhaozhou County Tai Ji village Tan spring rain is raised verifies as the cattle coccidiosis through local veterinary clinic diagnosis and animal and veterinary institute laboratory, Zhaozhou, Daqing.
4.1.2 medicine is used in test:
Trial drug: self-control paraformaldehyde preparation: see embodiment 1.
Drugs compared: the former powder of sulfamethazine.Dongming, Jiangxi Pharmaceutical Co., Ltd produces, pharmaceutical grade, lot number: 20060105.
4.2 test method and process
Test grouping and administration:
Take out at two in 42 sick cattle that the state of an illness is heavier, and other 40 sick cattle are divided into first and second liang of groups at random, and the first group is used the paraformaldehyde preparation for formaldehyde preparation test administration group, contains formaldehyde material per kilogram of body weight 0.02g oral administration by real, once a day; The second group contrasts the administration group for using the sulfamethazine treatment, according to per kilogram of body weight administration 0.1g oral administration, and twice of every day.
Two groups of successive administration drug withdrawals after 3 days, row was observed 7 days again.
Curative effect determinate standard: after the administration, the egg capsule in the spirit of observation every day and check cattle, hemafecia, the feces and the variation of aspects such as appetite, body temperature, heart and breathing, record.Dead cattle is determined its cause of death by cuing open to pick up with the laboratory assay.
Wherein:
1. cure: sick cattle medication after 3 days hemafecia stop, overall health of patients is good, feces does not have egg capsule discharges, it is no abnormal to continue 7 days viewing durations.
2. produce effects: sick cattle medication after 3 days hemafecia stop, overall health of patients is good, has egg capsule to discharge in the feces.Continuing 7 days viewing durations does not have the disease symptom appearance again, and no egg capsule is discharged in the feces.
3. invalid: sick cattle administration after three days hemafecia do not stop, continue to observe again after 7 days to off-test, still have egg capsule to discharge in the feces.
4. dead: the death of sick cattle duration of test, through clinical symptoms record before death and cut open the inspection result and be diagnosed as because of suffering from coccidiosis and directly cause death.
4.3 result of the test:
Table 4. substance formaldehyde is treated calf coccidiosis comparative test result with using sulfamethazine
| Group | The cattle number | Recovery from illness | Produce effects | Invalid | Dead |
| First | 20 | Number | Ratio (%) | Number | Ratio (%) | Number | Ratio (%) | Number | Ratio (%) |
| 20 | 100 | - | - | - | |||||
| Second | 20 | 13 | 65 | 3 | 15 | 3 | 15 | 1 | 5 |
X2=8.188, p＜0.05, as can be seen from the above table: use the first group effect of formaldehyde material treatment very effective, obviously be better than the second group of using this disease conventional medicament sulfamethazine of treatment.
Several relevant issues when (two) substance formaldehyde is used for purposes involved in the present invention:
1. owing to the weak zest of paraformaldehyde with than formability, recommend to use paraformaldehyde to prepare preparation involved in the present invention.
2. in purposes involved in the present invention was implemented, the suggestion formulation components can use:
1. be purpose to eliminate zest, increase palatability etc., preferably it made coated granule and coated tablet according to conventional packaging technique.By repeatedly practice, it is best to feel that paraformaldehyde is made granule with Polyethylene Glycol (4000-6000) parcel.The professional can be as the case may be during concrete enforcement, adds other component under the disadvantageous physical and chemical reaction prerequisite not surmounting not produce between the scope of the invention and each component.
2. in preparation, add alkaline matter with improve formaldehyde material pharmacological action and paraformaldehyde by depolymerization, secondly first-selected sodium carbonate is sodium bicarbonate.Its amount is to be advisable in about 0.5: 1 according to the ratio with the formaldehyde material, uses the latter appropriateness to increase to 0.7: 1.
3. when the preparation of preparation batch mixing, granule is made granularity as far as possible and be advisable near feed granules.Should be during use at the capable again spice in the preceding scene of feeding, in order to avoid material in the feedstuff and formaldehyde material react and influence drug effect.
Since the formaldehyde material be easy to react with multiple materials such as strong oxidizers, itrogenous organic substance, so for the selection of formaldehyde substance preparation component, carrier and excipient etc. the time, to avoid using might with the material of formaldehyde material generation adverse effect.
5. individual dosage and other: the extensive chemical that has in view of formaldehyde, in digestive tract, there is a small amount of existence can reach administration purpose of the present invention, so when concrete operations, can implement with reference to the oral individual dosage of stipulating in the existing national veterinary drug allusion quotation of formalin and other regulation.
Claims (1)
1. substance formaldehyde is as the purposes of unique active component in preparing the medicine of preventing and treating animal's coccidiosis by the digestive tract administration.
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Non-Patent Citations (2)
| Title |
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| 张龙现 等.抗兔球虫药物的种类及其临床应用效果评价.中国养兔杂志.1998,(6),29. |
| 张龙现等.抗兔球虫药物的种类及其临床应用效果评价.中国养兔杂志.1998,(6),29. * |
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