New use of n,2-dihydroxybenzamide

Abstract

The application discloses application of N,2-dihydroxybenzamide in preparation of a medicine for preventing and treating chicken coccidiosis. It is found that the N,2-dihydroxybenzamide has the characteristics of preventing and treating chicken coccidiosis, and has the characteristics of good prevention and treatment effect and small dosage compared with existing medicines for preventing and treating chicken coccidiosis.

Description

Technical Field

[0001] This invention belongs to the field of veterinary drug technology, specifically relating to new uses of N,2-dihydroxybenzamide, and more specifically to the application of N,2-dihydroxybenzamide in the prevention and treatment of coccidiosis in chickens. Background Technology

[0002] Coccidia are protozoan parasitic spore-forming microorganisms that live within the intestinal wall cells of livestock and poultry. Biologically, they belong to the order Coccidia. Coccidia multiply within host cells, causing cell rupture and releasing lysed spores that infect other cells. The life cycle of a coccidia consists of two phases: the lytic phase and the sporulation phase. The lytic phase is when the coccidia multiply rapidly within the host cell, while the sporulation phase is when lysed spores are released to infect other cells.

[0003] Coccidia are widely distributed, especially common in warm, humid environments. Due to their strong adaptability to the environment, coccidia frequently cause serious intestinal diseases in poultry farming. In chickens, ducks, geese, and other poultry, coccidiosis is one of the most common parasitic diseases, severely impacting poultry health and production performance.

[0004] Coccidiosis in chickens is widespread and highly damaging, with morbidity and mortality rates reaching as high as 80% in chicks aged 10-30 days or young chickens aged 35-60 days. Recovered chicks experience stunted growth and slow weight gain; adult chickens generally do not develop the disease but are carriers, experiencing reduced weight gain and egg production, and are a significant source of transmission for coccidiosis. Globally, coccidiosis causes approximately £2 billion in losses annually. In my country, the average annual cost of preventative medication for this disease is 0.2-0.3 yuan per chicken, amounting to hundreds of millions of yuan annually, accounting for nearly one-third of all chicken disease prevention and control costs. For a long time, the main means of controlling coccidiosis has been the use of antibiotics and chemically synthesized drugs. While these drugs have played a crucial role in the prevention and control of coccidiosis, the development of drug resistance in coccidia has been a persistent problem for farmers and veterinarians. Some flocks, despite using anticoccidial drugs, still face the threat of coccidiosis outbreaks. In recent years, research on immunization against coccidiosis in chickens has made some progress, but its widespread application still faces some challenges. For a considerable period of time, medication will remain the primary weapon in the prevention and control of coccidiosis in chickens.

[0005] N,2-Dihydroxybenzamide, also known as salicylhydroxyoxime acid, o-hydroxybenzoylhydroxyoxime acid, etc., is an important intermediate commonly used in chemical synthesis and pharmaceutical manufacturing. Summary of the Invention

[0006] The purpose of this invention is to solve the problem of coccidiosis in chickens and to provide the application of N,2-dihydroxybenzamide in the prevention and treatment of coccidiosis in chickens.

[0007] The objective of this invention is specifically achieved through the following technical solutions:

[0008] Application of N,2-dihydroxybenzamide in the preparation of drugs for the prevention and treatment of coccidiosis in chickens.

[0009] Preferably, the coccidiosis in chickens includes, but is not limited to, Eimeria giant coccidiosis.

[0010] This invention discovers that N,2-dihydroxybenzamide has good activity in preventing and treating coccidiosis in chickens, and can be used as a novel drug for the prevention or treatment of coccidiosis in chickens. Detailed Implementation

[0011] The preferred embodiments of the present invention are described below. It should be understood that the preferred embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0012] Example 1

[0013] Clinical trials of compounds for the prevention and treatment of coccidiosis in chickens:

[0014] 1. Materials and Methods:

[0015] 1.1 Coccidia oocysts:

[0016] Giant Eimeria oocysts were provided by the Shanghai Veterinary Research Institute of the Chinese Academy of Agricultural Sciences. Before the experiment, chickens without coccidia were artificially infected and subcultured once to obtain experimental oocysts. These oocysts were cultured at 29°C until sporulation, and then stored at 4°C for later use. Sulfachloropyrazine sodium and N,2-dihydroxybenzamide were both commercially available products.

[0017] 1.2 Grouping and treatment of experimental animals:

[0018] One-day-old male Liangfenghua broiler chicks were purchased from a breeding farm in Guangzhou. Immediately after hatching, they were placed in special chick boxes and transported back to the farm. They were raised in strictly disinfected, coccidioidom-free cages, fed only complete brooder pellet feed without any added drugs, and allowed free access to food and water. At 11 days of age, 40 chicks of similar body weight, confirmed healthy through observation, were randomly divided into four groups of 10 chicks each. Group I served as a negative control group, Group II as a positive control group, Group III received sodium sulfachlorpyrifos at 2g per kilogram of feed, and Group IV received N,2-dihydroxybenzamide at 50mg per kilogram of feed. Control groups I and II had free access to food and water; groups III and IV received the corresponding drugs in their feed until culling. At 14 days of age, chicks in groups II-IV were infected with 1.0 × 10⁻¹⁰ Eimeria giantiformis sporulated oocysts. 5 Each chicken was infected individually, and all experimental chickens were culled on the 8th day after infection. Chickens were weighed on an empty stomach on the day of infection and again on the 8th day after infection.

[0019] 1.4 Clinical symptom observation:

[0020] After coccidiosis inoculation, the incidence and clinical symptoms of chickens in each group were observed and recorded daily. Feces were examined daily on days 4, 5, 6, and 7 post-infection, and bloody stools were recorded. Oocysts were counted, and dead chickens were promptly necropsied to determine the cause of death.

[0021] 1.5 Evaluation Indicators and Standards for Compound Therapeutic Effects:

[0022] 1.5.1 Survival rate:

[0023] Survival rate (%) = Number of surviving chickens / Total number of experimental chickens × 100%.

[0024] 1.5.2 Relative weight gain rate:

[0025] Relative weight gain rate (%) = Weight gain rate of the drug-treated group or the infection-free group / Weight gain rate of the infection-free group × 100%.

[0026] 1.5.3 Lesion scoring and lesion value:

[0027] The lesion was scored according to the 5-point scoring system of Johnson et al., based on the severity of intestinal lesions after necropsy.

[0028] 0 points: No visible lesions;

[0029] 1 point: There are very few scattered punctate hemorrhages in the intestinal wall, the intestinal wall is not thickened, and the contents are normal;

[0030] 2 points: The intestinal contents contain a small amount of blood, the intestinal wall is thickened, and multiple bleeding lesions are visible;

[0031] 3 points: There is a large amount of blood or intestinal nodules (blood clots or grayish-white, cheese-like banana-shaped masses) in the intestines, and the intestinal walls are thickened and obviously deformed and atrophied;

[0032] 4 points: Significant intestinal atrophy, extremely thickened intestinal wall, blood clots or intestinal nodules in the intestine. When making a judgment, sometimes the lesions of the two cecums are inconsistent, so the side with more severe lesions should be used as the standard for judgment.

[0033] Lesion value = average lesion score for each group × 10.

[0034] 1.5.4 Oocyte count:

[0035] The values ​​were converted based on Kiyoshi Kakuda's method of Oocysts per gram feces (OPG). When the OPG value is 0.00–0.10, the Oocyst value is 0; when the OPG value is 0.11–1.00, the Oocyst value is 1; when the OPG value is 1.10–1.90, the Oocyst value is 10; when the OPG value is 2.00–5.90, the Oocyst value is 20; when the OPG value is 6.00–10.90, the Oocyst value is 30; and when the OPG value is ≥11.0, the Oocyst value is 40.

[0036] 1.5.6 Anticoccidial Index (ACI):

[0037] The anticoccidial index (ACI) was calculated according to the standards of Merck & Co., Ltd. Anticoccidial Index (ACI) = (Relative weight gain rate + Survival rate) - (Lesion value + Oocyst value + Bloody stool score). The efficacy evaluation criteria were as follows: an ACI less than 120 was considered poor efficacy; an ACI between 120 and 160 was considered moderate efficacy; an ACI between 160 and 180 was considered good efficacy; and an ACI greater than 180 was considered excellent efficacy.

[0038] 2. Results:

[0039] 2.1 Clinical symptoms:

[0040] On the 4th day after coccidiosis inoculation, except for the negative control group, chickens in other groups showed varying degrees of clinical symptoms, such as poor mental state, depression, lethargy, reduced feed intake, ruffled feathers, drooping wings, retracted head and neck, closed eyes and drowsiness, reluctance to move, standing alone and isolated, and bloody feces. On the 5th and 6th days after inoculation, chickens in the positive control group excreted a large amount of bloody feces, while the bloody feces in the treated groups were less than those in the positive control group, and one chicken in group II died. On the 7th day after inoculation, the bloody feces decreased, and one chicken in group II died. The mortality rates of groups I to IV were 0%, 20%, 0%, and 0%, respectively, and the average bloody feces scores were 0, 2.4, 1, and 1, respectively.

[0041] 2.2 Experimental Results

[0042] The results of the clinical trial are shown in Table 1.

[0043] Table 1 Results of the anticoccidial activity of the compounds

[0044] Group I 100 100 0 0 0 200 Group II 80 64.5 40 21 2.4 81.1 Group III 100 82.1 10 11 1 160.1 Group IV 100 83.1 10 7 1 165.1

[0045] The results of this experiment show that the ACI value of compound N,2-dihydroxybenzamide is 165.4, which is higher than that of sodium sulfachlorpyrifos (160.1), indicating that this compound has a good anticoccidial effect. Furthermore, the amount of N,2-dihydroxybenzamide added to feed is significantly less than that of sodium sulfachlorpyrifos. N,2-dihydroxybenzamide can be used as a drug for the prevention and treatment of coccidiosis in chickens, characterized by its good anticoccidial effect and low dosage.

[0046] Histone deacetylases (HDACs) play a crucial role in chromatin distribution and gene regulation, and are novel targets for the treatment of cancer and parasites. Hydroxime acid inhibitors are currently the most studied histone deacetylase inhibitors. N,2-Dihydroxybenzamide is a common, inexpensive, and readily available biochemical analytical reagent. Its efficacy in preventing and treating coccidiosis in chickens may be related to the structure of the hydroxime acid, and its modification shows promise in obtaining novel anticoccidial drugs with good anti-coccidial effects.

[0047] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Application of N,2-dihydroxybenzamide in the preparation of drugs for the prevention and treatment of coccidiosis in chickens.

2. The application according to claim 1, characterized in that: The coccidiosis in chickens mentioned is Eimeria giantis infection.