CN110269853B - Application of galopam in preparation of medicine for resisting coccidiosis - Google Patents

Application of galopam in preparation of medicine for resisting coccidiosis Download PDF

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CN110269853B
CN110269853B CN201910543825.0A CN201910543825A CN110269853B CN 110269853 B CN110269853 B CN 110269853B CN 201910543825 A CN201910543825 A CN 201910543825A CN 110269853 B CN110269853 B CN 110269853B
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galopam
feed
coccidiosis
anticoccidial
chicken
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CN110269853A (en
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王彦辉
李自波
刘兵
李国辉
焦金英
孙少辉
孟祥�
张宁
姬星宇
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Henan Yeehua Animal Pharmaceutical Co ltd
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Henan Yeehua Animal Pharmaceutical Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/275Nitriles; Isonitriles
    • A61K31/277Nitriles; Isonitriles having a ring, e.g. verapamil
    • 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/63Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • A61P33/02Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis

Abstract

The invention relates to the field of biomedicine, in particular to application of galopam in preparing a medicine for resisting chicken coccidiosis injury. The galopam is used for preparing medicines for resisting coccidiosis. In particular to a chicken coccidium injury resistant medicine prepared by compounding galopam and a conventional coccidium resistant medicine. The invention applies the galopam to the chicks infected with the coccidiosis of the chickens, finds that the lesion value of the chicks can be obviously reduced, has the damage-resistant function on the damaged tissues, and cannot cause the influence on the growth and development caused by the slow repair of the damage of animal organisms; compared with the sick chicks fed with the feed only containing the anticoccidial drugs, the relative weight gain rate of the sick chicks fed with the feed containing the anticoccidial drugs and the galopamid feed is improved by 3.89-8.15 percent; compared with sick chicks fed with the feed without the medicines, the relative weight gain rate of the sick chicks fed with the feed containing the anticoccidial medicines and the galopam feed is improved by 18.08-22.34 percent.

Description

Application of galopam in preparation of medicine for resisting coccidiosis in chicken
Technical Field
The invention relates to the field of biomedicine, in particular to application of galopam in preparing a medicine for resisting coccidiosis.
Background
Chicken coccidiosis is a parasitic protozoal disease caused by one or more of Eimeria in chicken intestinal mucosal epithelium, and is one of the diseases causing the largest economic loss in modern poultry industry. Chicks mainly invade within 3 months of age, and often cause serious damage to small intestines or cecum and areas nearby the small intestines, such as bleeding, necrosis, catarrhal inflammation and the like, and the enduring sick chickens cannot recover for a long time, the weight gain is reduced, the growth and development are seriously hindered, the adult chickens are less ill, but become carriers, the physique and the egg laying capacity of the adult chickens can be affected, and huge economic loss is often brought to the chicken industry.
At present, chicken coccidiosis is mainly prevented and treated by using medicines, the existing anticoccidial medicines such as sulfa drugs, triazines, dinitriles and the like mainly act on coccidia at a certain growth stage to inhibit or kill the coccidia, and the medicines have no damage resistance effect on damaged tissues, easily cause slow repair due to damage of animal organisms, influence on growth and development and bring certain economic loss. Therefore, in the process of preventing and treating chicken coccidiosis, coccidiosis resistance and damage resistance are necessary.
Galopamide (CAS:0016662-47-8, molecular weight 485, chemical formula C28-H40-N2-O5, chemical structure as follows:
Figure BDA0002103385260000011
the clopamil is a calcium channel blocker, can relax blood vessels and reduce blood pressure; can inhibit the automatic rhythm of the sinus node of the heart and slow down the heart rate, can be used for preventing and treating angina, and has not been reported to have anticoccidial injury.
Disclosure of Invention
In order to solve the problem that the anticoccidial drug can not repair the tissue damage caused by the coccidiosis of the chicken, the invention provides the application of the galopamid in preparing the anticoccidial drug.
The invention adopts the following technical scheme:
application of galopam in preparing medicine for treating chicken coccidiosis is disclosed.
Further, the method specifically comprises the following steps: the preparation method comprises the step of mixing the galopam, the anticoccidial drug and auxiliary materials to prepare the anticoccidial drug, wherein the anticoccidial drug is a sulfonamide compound, a triazine compound, a quinolone compound, a polyether ionophore robenidine, amproline and a compound preparation thereof, a plant alkali compound or nicarbazin.
Further, the sulfonamide compound is sulfaquinoline, sulfachloropyrazine, sulfadimetrazine or sulfamonomethoxine, the triazine compound is toltrazuril or diclazuril, the quinolone compound is benmethoquinate, decoquinate or butoxyquinate, and the plant alkali compound is halofuginone.
Further, the anti-coccidiosis drug is powder; when the powder is used, the powder is mixed with feed, and the addition amount of the galopamid in the feed is 5-15 mg/kg.
Further, the auxiliary material is any one of oral glucose, anhydrous glucose, maltodextrin, soluble starch, maltose, sucrose, corn starch, corncob meal, corn flour and bran.
After the coccidian infects the chicken, the calcium granules in the epithelial cells of the intestinal tissue are obviously increased and show a continuously increased state, and the free Ca in the host cells 2+ The content is obviously increased. Ca 2+ Ca caused by overload 2+ Dependent phospholipase A enzymes 2 The activity of the compound is obviously improved, so that the membrane phospholipid is degraded, the content of free fatty acid of a degradation product is obviously increased, and the damage of host cells is aggravated.
Calcium channel blocker galopamid Ca 2+ Reduced influx and decreased phospholipase A due to calcium overload 2 The activity of the chicken feed can further reduce the content of free fatty acid, thereby reducing the damage of host cells and protecting the chicken bodyThe application is as follows.
The invention has the following beneficial effects:
the invention applies the galopam to the chicks infected with the chicken coccidiosis, and finds that the lesion value of the chicks can be obviously reduced, which indicates that the galopam repairs the problem of tissue damage caused by the chicken coccidiosis; compared with sick chicks fed with the feed only containing the anticoccidial drugs, the relative weight gain rate of the sick chicks fed with the feed containing the anticoccidial drugs and the galopam feed is improved by 3.89-8.15%; compared with sick chicks fed with the feed without the medicine, the relative weight gain rate of the sick chicks fed with the feed containing the anticoccidial agent and the galopam feed is improved by 18.08-22.34 percent. In addition, the anticoccidial agent and the clopamil act together, so that the anticoccidial index of the chicks can be improved to 184.04-190.37.
Detailed Description
The invention is further described below with reference to specific embodiments. It is to be understood that the examples are illustrative only and are not to be construed as limiting the scope of the invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be within the scope of the invention.
Example 1
Preparation of drug a: mixing 60g of sulfachloropyrazine sodium, 12g of dimethoxypyrimidine, 0.5g of clopamil and 127.5g of auxiliary materials to obtain an anti-coccidiosis chicken drug A;
preparation of drug B: mixing 60g of sulfachloropyrazine sodium, 12g of dimethoxypyrimidine, 1g of galopam and 127g of auxiliary materials to obtain a chicken coccidium damage resistant medicament B;
preparation of drug C: mixing 60g of sulfachloropyrazine sodium, 12g of dimethoxypyrimidine, 1.5g of galopamid and 126.5g of auxiliary materials to obtain an anti-coccidiosis chicken drug C;
the anticoccidial injury medicines are all powder, and the auxiliary material is any one of oral glucose, anhydrous glucose, maltodextrin, soluble starch, maltose, sucrose, corn starch, corncob powder, corn flour and bran.
The usage and dosage are as follows: 200g of the medicine is mixed with 100kg of feed, and the feed is fed according to the normal feed intake and is freely taken.
Example 2
In this example 11 day old healthy chicks were provided by the bioengineering company ltd, meilan, and were healthy and free from coccidian infection by stool examination. Coccidian oocysts were isolated and preserved by Henan Yihua animal pharmaceutical Co., Ltd, and galopam, sulfachloropyrazine sodium and dimethoxypyrimidine were provided by Henan Yihua animal pharmaceutical Co., Ltd.
Mixing 60g of sulfachloropyrazine sodium, 12g of dimethoxypyrimidine and 128g of auxiliary materials to prepare a medicine D; the drug D and the drug A, the drug B and the drug C prepared in example 1 were mixed with 100kg of feed in a manner of mixing 200g of the drug with feed to prepare feed D, feed A, feed B and feed C.
Healthy chicks of 11 days old are selected, numbered one by one and weighed on an empty stomach, chicks with too small and too large weights are eliminated, the chicks are randomly divided into 4 groups according to weight dispersion, 15 chicks are arranged in each group, the first group is a blank control group, the second group is feed D after infection for 72h, the third group is feed A after infection for 72h, the fourth group is feed B after infection for 72h, the fifth group is feed C after infection for 72h, and the sixth group is a medicine-free group after infection. The animals were fed daily until the end of the experiment and were fed ad libitum. The second, third and fourth groups were each chickens orally administered coccidian sporulated oocysts at 12 days of age 4 One/only. During the test period, the mental state, the ingestion condition, the morbidity and the death condition of the chicken flocks are observed every day, and meanwhile, the feces on the 5 th to 7 th days are collected and used as the gram feces oocyst count (OPG). Weighing 8 days after infection, killing, observing and recording the intestinal lesion value. The anticoccidial index was calculated according to the method of "coccidiosis in chicken" (edited by Suo, Lizhou Qing dynasty, China agricultural university Press, 1998). And C, immediately performing autopsy on the dead chickens in the test process, and judging whether the dead chickens die of the coccidiosis. The feed is a gift from bioengineering, ltd, of Shangqin Meilan, and contains no anticoccidial.
The lesion value is: in the chicken coccidiosis infection, the pathological changes of intestinal tracts are classified into five grades of 0, 1, 2, 3 and 4 according to the presence or absence of the pathological changes.
0 point, no macroscopic lesions.
For 1 minute, there were very few scattered petechiae on the intestinal wall, the intestinal wall did not thicken, and the contents were normal.
2 points, the pathological changes are more, the intestinal contents are obviously bloody, the intestinal wall is slightly thickened, and the contents are normal.
3 min, large amount of blood or blood clots or off-white cheese-like lumps in the intestine), marked thickening of the caecum wall, and low fecal content in the caecum.
4 points out that the cecum is swollen because of being filled with a large amount of blood or the intestinal core, and the intestinal core contains feces or does not contain feces.
The deaths were scored 4 points for coccidia infection.
Lesion score-mean lesion score of chickens per group x 10,
anticoccidial index ACI ═ (relative rate of gain + survival) × 100- (lesion value + oocyst value).
ACI > 180 is judged to be sensitive, ACI <180 > 160 is good, ACI <160 > 120 is poor, and ACI <120 is invalid.
TABLE 1 anticoccidial index test results
Figure BDA0002103385260000041
The higher the anticoccidial index is, the better the anticoccidial effect is; the lesion value reflects the degree of damage caused by chicken coccidiosis, and a higher lesion value indicates more serious damage. The above results show that: after the clopamil is added, the lesion value is reduced compared with that of a group without the clopamil, and the corresponding anticoccidial index is improved by 30.14-36.47, which shows that the clopamil plays a role in resisting the coccidian injury of chickens.
The above-mentioned embodiments are only preferred embodiments of the present invention, and are only used for explaining the present invention, and not for limiting the scope of the present invention, and it is obvious to those skilled in the art that other embodiments can be easily made by replacing or changing the technical content disclosed in the present specification, and therefore, all changes and modifications made in the principle and process conditions of the present invention should be included in the scope of the present invention.

Claims (3)

1. The application of the galopamid in preparing the medicine for resisting the coccidiosis in chicken is characterized in that the medicine for resisting the coccidiosis in chicken infected with the coccidiosis in 5-7 days specifically comprises the following steps: the clopamil, the anticoccidial drugs and the auxiliary materials are mixed to prepare the anticoccidial drug, wherein the anticoccidial drugs are sulfachloropyrazine sodium and dimethoxypyrimidine.
2. The use of galopam in the preparation of an anti-coccidial injury medicament of claim 1, wherein the anti-coccidial injury medicament is a powder.
3. The use of galopam in the preparation of a medicament for treating coccidiosis in chicken according to claim 2, wherein the excipient is any one of oral glucose, anhydrous glucose, maltodextrin, soluble starch, maltose, sucrose, corn starch, corncob meal, corn meal and bran.
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CN102247386A (en) * 2011-05-26 2011-11-23 河南牧翔动物药业有限公司 Soluble powder used for treating poultry coccidiosis

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Publication number Priority date Publication date Assignee Title
CN102247386A (en) * 2011-05-26 2011-11-23 河南牧翔动物药业有限公司 Soluble powder used for treating poultry coccidiosis

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* Cited by examiner, † Cited by third party
Title
细胞钙超载与鸡E.tenella病损伤机制的研究;范运峰;《农业科技辑》;20050731;摘要 *
细胞钙超载与鸡柔嫩艾美耳球虫病损伤关系;郑明学等;《全国兽医病理学、动物病理生理学学术会议论文集》;20090701;第301-304页 *
胞外钙和钙通道与鸡盲肠上皮细胞内游离钙离子浓度的关系;崔小珍等;《2013年中国畜牧兽医学会兽医病理学分会暨中国病理生理学会动物病理生理学专业委员会学术研讨会》;20130801;全文 *

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