CN114948867A

CN114948867A - Niclosamide or salt oral liquid thereof for livestock and poultry as well as preparation method and application thereof

Info

Publication number: CN114948867A
Application number: CN202210869699.XA
Authority: CN
Inventors: 刘淑鹤; 王清玲; 何柏江; 高淑娟; 金顺义
Original assignee: Henan Senlong Animal Health Product Co ltd
Current assignee: Henan Senlong Animal Health Product Co ltd
Priority date: 2022-07-22
Filing date: 2022-07-22
Publication date: 2022-08-30

Abstract

The invention provides niclosamide or salt oral liquid for livestock and poultry and a preparation method thereof, relating to the technical field of veterinary drug preparations and comprising the following components (by weight percent): 3-10% of niclosamide or salt thereof, 1-4% of surfactant, 20-70% of composite non-aqueous solvent, 0.02-0.5% of stabilizer, pH regulator for regulating pH to 8.0-9.0, and purified water with constant volume of 100%. The invention provides a novel niclosamide preparation which can be used for both group medication and oral medication of large animal individuals for veterinary clinical in the breeding industry, and experiments prove that: the preparation has stable property, no obvious content change (the content is reduced by less than 10%) after being placed at room temperature for one year, good drug effect and high safety, and has important application value in the field of veterinary drugs.

Description

Niclosamide or salt oral liquid for livestock and poultry as well as preparation method and application thereof

Technical Field

The invention relates to the technical field of veterinary drug preparations, in particular to niclosamide or salt oral liquid thereof for livestock and poultry, and a preparation method and application thereof.

Background

Niclosamide (Niclosamide) is a traditional oral anthelmintic drug, has been used for over 50 years in clinic, is commonly used for treating various taeniasis, is widely used for preventing and treating human schistosomiasis as a molluscicide, and has an antiparasitic mechanism which is considered to inhibit oxidative phosphorylation of mitochondria and ATP (adenosine triphosphate) production of anaerobic bacteria. In recent years, domestic and international researches show that niclosamide also has the effects of widely resisting tumors and broad-spectrum viruses, enhancing the antibacterial activity of antibacterial drugs and reversing the drug resistance of bacteria. Niclosamide has the advantages of low toxicity, high safety to human and livestock, low price and the like, but has poor solubility and low bioavailability, and limits the exertion of clinical antitumor, antiviral, antibacterial curative effect enhancement and the like.

Niclosamide is a salicylanilide derivative which is almost insoluble in water, only slightly soluble in ethanol and has unstable amido bond in a molecular structure, so that the niclosamide is difficult to prepare liquid formulations such as oral liquid or injection and the like. The common preparation formulation approved for clinical use at present is a tablet, the preparation formulation is single, livestock can only be administrated by individuals, the use is very inconvenient, and the tablet is not suitable for poultry flocks or herds which are raised in an intensive and large-scale manner. In order to improve the water solubility, the dosage form research and patent reports paste, wettable powder, niclosamide and ethanolamine suspending agent, suspension emulsion, nano preparation, slow release agent, controlled release agent, spray, hydroxypropyl beta-cyclodextrin compound and the like, and the reported dosage forms have high cost or water solubility which does not meet the requirement of medication, so the dosage forms are difficult to use in poultry or livestock raised on a large scale. So far, there are no patents and literature reports on solutions such as oral liquid and injection.

Disclosure of Invention

Aiming at the problems and the blank of the prior art, the niclosamide or the salt oral liquid thereof has stable physical and chemical properties, is safe and effective, and can be taken by livestock and poultry groups for drinking and can be orally taken for individual treatment.

The technical scheme is as follows: the niclosamide or salt oral liquid comprises the following components in percentage by weight: 3-10% of niclosamide or salt thereof, 1-4% of surfactant, 20-70% of composite non-aqueous solvent, 0.02-0.5% of stabilizer, pH regulator for regulating pH to 8.0-9.0, and purified water with constant volume of 100%.

Preferably, the salt may be niclosamide ethanolamine, niclosamide piperazine, or niclosamide phosphate.

Preferably, the surfactant is one of sodium dodecyl sulfate, tween-80, tween-40, tween-20, peregal O, polyoxyethylene 40 stearate, poloxamer 188, maize 51, maize 52 and dioctyl sodium sulfa succinate.

Preferably, the composite non-aqueous solvent is 2 to 3 combinations of ethanol, PEG400, α -pyrrolidone, glycerol formal, dimethylformamide, dimethylacetamide, DMSO (dimethyl sulfoxide), propylene glycol, and glycerol; the ratio of the composite non-aqueous solvent to the non-aqueous solvent is 5: 1-1: 5 when the composite non-aqueous solvent is 2 combinations, and the ratio of the composite non-aqueous solvent to the non-aqueous solvent is 4:1: 1-1: 4: 1-1: 1:4 when the composite non-aqueous solvent is 3 combinations.

Preferably, the stabilizer is 2 combinations of EDTA-2Na, calcium sodium edetate, sodium tripolyphosphate, sodium sulfite, sodium formaldehyde sulfoxylate, thiourea and sodium thiosulfate.

Preferably, the pH regulator is one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, meglumine, triethanolamine, ethanolamine, and ethylenediamine.

The oral liquid prepared by the invention has stable quality, is clear and transparent, is stable in the process of placement, does not precipitate after being diluted by normal water and placed for 24 hours, and is suitable for being mixed with the group for drinking.

The invention provides a preparation method of niclosamide or salt oral liquid thereof for livestock and poultry, which comprises the following specific preparation processes:

step (1): mixing niclosamide or salt thereof with surfactant, adding into the mixed non-aqueous solvent, and stirring to obtain solution A;

step (2): dissolving the stabilizer in a proper amount of purified water, and uniformly stirring to obtain a solution B;

and (3): dissolving a pH regulator in a proper amount of purified water, and stirring and dissolving to obtain a solution C;

and (4): adding the solution B into the solution A while stirring, and uniformly mixing to obtain solution D;

and (5): adding the solution C into the solution D while stirring, stirring for dissolving, adjusting the pH value to 8.0-9.0, and fixing the volume of purified water to 100mL to obtain clear, transparent and light red solution E;

and (6) filtering the solution E, subpackaging, sealing in a brown bottle, keeping out of the sun, and storing in shade.

The niclosamide or the salt oral liquid thereof provided by the invention can be used for treating cestodiasis and molluscacidal of livestock and poultry, and can be used as a new medicine for other purposes, such as: anti-tumor, anti-virus (coronavirus, flavivirus, avian influenza virus, etc.), and antibacterial activity of antibiotics such as colistin.

The oral liquid is clear and transparent, and has good physical and chemical stability, wherein:

(1) long-term standing stability at room temperature:

storing the product for one year at room temperature of 15-35 ℃ in the dark, and the product has no turbid precipitate, no obvious change in color and no content reduction of more than 4% (more than 96%).

The product is stored in a refrigerator at 4 ℃ in dark for 6 months, has stable properties, no obvious color change and no precipitation.

(2) Freeze resistance stability:

the oral liquid can be stored in a refrigerator at-15 deg.C for 1, 7, 15, 1, 2, 3, 4, and 6 months without freezing and turbidity, and is suitable for cold storage, transportation, and application.

(3) Mixing and drinking stability:

the oral liquid is respectively taken according to the recommended dosage concentration (250ppm) and the concentration 2 times, 4 times, 10 times and 20 times of the recommended concentration, diluted by normal water (namely 2kg of water (250ppm), 1kg of water (500ppm), 0.5kg of water (1000ppm), 0.2kg of water (2500ppm) and 0.1kg of water (5000ppm) are respectively mixed in each 10 mL), uniformly mixed, placed for 24 hours without precipitation, the physical properties are stable after the oral liquid is mixed and diluted by natural normal water in different proportions, and the oral liquid is suitable for intensive poultry herds and herds to be mixed and drunk in different proportions.

(4) The safety is high:

the 5% oral liquid is mixed with 1 time (250ppm), 3 times (750ppm), 5 times (1250ppm) and 10 times (5000ppm) of recommended dose for 1 week of healthy broiler chickens, and the feed intake, water intake and growth performance of test chickens are not obviously changed compared with those of a control group.

Compared with the prior art, the invention has the beneficial effects that:

(1) the invention is suitable for large-scale herds or poultry herds to drink the herds for medicine, and can also be used for large and medium-sized domestic animals to take individual medicine orally, and the dosage is easier to control accurately than tablets, and the use is more convenient;

(2) the oral liquid contains a surfactant and a non-aqueous solvent, and niclosamide or salt thereof is in a dissolved state, so that the oral liquid is beneficial to the medicine entering tapeworm bodies to play a role, is also beneficial to improving absorption and improving bioavailability;

(3) the invention is mixed into normal water in different proportions for stabilization, so clinically, the invention can be mixed and drunk in different proportions according to actual needs, so that animals can take medicines in different time by thirst mixing drinking, and the use is more agile;

(4) the oral liquid is alkalescent, so that the palatability and the drinking amount of animals are not influenced by mixed drinking after dilution.

Detailed Description

The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

In the invention: the niclosamide or niclosamide salt oral liquid comprises the following components in percentage by weight: 3-10% of niclosamide or salt thereof, 1-4% of surfactant, 20-70% of composite non-aqueous solvent, 0.02-0.5% of stabilizer, pH regulator for regulating pH to 8.0-9.0, and purified water with constant volume of 100%.

Wherein the salt is niclosamide ethanolamine, niclosamide piperazine, or niclosamide phosphate.

Wherein the surfactant is one of sodium dodecyl sulfate, Tween-80, Tween-40, Tween-20, peregal O, polyoxyethylene 40 stearate, poloxamer 188, maize 51, maize 52 and dioctyl sodium sulfa succinate.

Wherein, the composite non-aqueous solvent is 2 to 3 combinations of ethanol, PEG400, alpha-pyrrolidone, glycerol formal, dimethylformamide, dimethylacetamide, DMSO (dimethyl sulfoxide), propylene glycol and glycerol; the ratio of the composite non-aqueous solvent to the non-aqueous solvent is 5: 1-1: 5 when the composite non-aqueous solvent is 2 combinations, and the ratio of the composite non-aqueous solvent to the non-aqueous solvent is 4:1: 1-1: 4: 1-1: 1:4 when the composite non-aqueous solvent is 3 combinations.

Wherein the stabilizer is 2 combinations of EDTA-2Na, calcium disodium edetate, sodium tripolyphosphate, sodium sulfite, sodium formaldehyde sulfoxylate, thiourea and sodium thiosulfate.

Wherein the pH regulator is one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, meglumine, triethanolamine, ethanolamine and ethylenediamine.

Example 1: the niclosamide or salt oral liquid for livestock and poultry comprises the following components in percentage by weight: 3-10% of niclosamide, 2% of a surfactant (Tween-80), 60% of a composite non-aqueous solvent (dimethylformamide: PEG 400: ethanol 4:1:1), 0.22% of a stabilizer (EDTA-2Na 0.02% + sodium thiosulfate), and a pH regulator (meglumine) for regulating the pH to 8.0-9.0, wherein the purified water is added to a constant volume of 100%.

A method for preparing niclosamide or salt oral liquid thereof for livestock and poultry comprises the following steps:

(1) respectively and precisely taking 5g of niclosamide and 2g of surfactant, uniformly mixing, adding 60g of uniformly mixed composite non-aqueous solvent, stirring and uniformly mixing to obtain solution A;

(2) dissolving 0.02g of EDTA-2Na and 0.2g of sodium thiosulfate in a proper amount of purified water, and stirring to dissolve to obtain solution B;

(3) dissolving 5g of pH regulator in a proper amount (about 10 ml) of purified water, and stirring to dissolve to obtain solution C for later use;

(4) adding the solution B into the solution A while stirring, and uniformly mixing to obtain solution D;

(5) and adding the solution C into the solution D while stirring, stirring for dissolving, continuously adjusting the pH value to 8.0-9.0 by using the solution C, and fixing the volume of purified water to 100mL to obtain clear, transparent and light red solution E, namely the 5% niclosamide oral liquid for livestock and poultry.

Example 2: a method for researching the standing stability of niclosamide or its salt oral liquid (5%) for livestock and poultry comprises the following steps:

1 Material

1.1 test drugs: the oral liquid prepared according to the embodiment 1 is prepared by taking 5 percent of niclosamide by mass percent; niclosamide standard substance: the purity is 99.8%, and the product is obtained from Chinese drug accreditation institute (for measuring standard curve, recovery rate and precision).

Reagent: ultrapure water; methanol, acetonitrile (chromatographically pure); phosphoric acid (analytical grade).

1.2 Instrument: model AB204-N electronic analytical balance (Metler-Torili instruments Shanghai Co., Ltd.); DHG-9140A type vacuum drying oven (shanghai yi constant laboratory instruments ltd); micropipette (Eppendorf, Germany), ultrasonic cleaner (Wauter, Inc., Shanghai), high performance liquid chromatograph (Waters, USA), 2695 separation and autosampler system, 2487 dual wavelength ultraviolet detector, Em-power2 chromatographic workstation.

2 methods and results

2.1 preparation of the solution

2.1.1 control solutions: taking niclosamide as a reference substance, weighing accurately about 50mg, placing into a 100mL measuring flask, adding appropriate amount of methanol, performing ultrasonic treatment for 30min to dissolve, diluting with methanol to scale, and shaking up to obtain stock solution. Precisely measuring 1mL of niclosamide stock solution, placing in a 100mL measuring flask, adding methanol to desired volume, and shaking to obtain reference solution.

2.1.2 test article solution: precisely taking 1.0mL (equivalent to 50mg of niclosamide) of 5% niclosamide solution by mass, placing in a 100mL measuring flask, adding methanol, performing ultrasonic treatment for 30min to dissolve, diluting with methanol to scale, shaking, and filtering. Precisely measuring 1mL of the continuous filtrate, placing the continuous filtrate in a 100mL measuring flask, metering the volume to the scale with methanol, and shaking up to obtain the final product.

2.2 chromatographic conditions: a C18 column (250 mm. times.4.60 mm, 5. mu.M) was used; the mobile phase is methanol-0.1 percent phosphoric acid solution; gradient elution mode was used, flow rate: 1.2 mL/min; the ultraviolet detection wavelength is 230 nm; 20 μ L of sample was injected.

2.3 Linear relationship examination: precisely measuring the stock solutions 0.3 mL, 0.4 mL, 0.5 mL, 0.8 mL, 1.0mL, 1.5 mL and 2.0mL respectively, placing in a 100mL measuring flask, diluting with methanol to scale, and shaking; the solution was taken 20. mu.L each and injected into a liquid chromatograph (3 repeated injections were performed for each concentration point), and the average was taken according to the peak area measured. And performing linear regression on the concentration C (mu g/mL) by using the peak area A to obtain a standard curve, wherein the quantitative linear range is 1.5-10 mu g/mL. A standard curve is made before each sample measurement.

2.4 precision test: precisely measuring 20 mu L of the same test solution, continuously and repeatedly injecting for 6 times, and measuring the Relative Standard Deviation (RSD) of the niclosamide peak area to be 0.7%.

2.6 repeatability test: precisely measuring 5 parts of the same batch of samples, preparing a sample solution according to a method of 2.1.2, and respectively measuring the average content of niclosamide to be 100.75% and the average content of RSD to be 1.32% under the condition of 2.2 chromatography.

2.7 stability test: precisely sucking 20 μ L of test solution, injecting into high performance liquid chromatograph for 0, 2, 4, 8, 10, 12, and 24h, and measuring to obtain niclosamide with RSD of 0.8%. The results show that the test solution is stable within 24 h.

2.8 recovery test: the recovery test was carried out by using the blank addition recovery method according to the recipe of example 1, i.e., adding the control to the solvent of the blank recipe. 3 parts of test solution with high, medium and low concentrations (corresponding to 120%, 100% and 80% of the measured concentration) are prepared respectively, the content is measured, and the recovery rate is calculated. The results showed that the recovery rates of niclosamide at high, medium and low levels (n: 4) were 101.3%, 98.5% and 99.1%, respectively.

2.9 sample determination: and precisely absorbing 20 mu L of each of the reference solution and the test solution for triple sample feeding determination after the samples are placed in the dark at room temperature for 1-12 months, substituting the average peak area measured by an external standard method into the time point standard curve, and calculating the niclosamide content in the samples. Meanwhile, the change of color and precipitation are observed. The results are shown in Table 1.

TABLE 1 determination of the content of niclosamide or its salt in oral liquid by keeping it warm and dark (μ g/mL)

2.10 Observation of stability and anti-freezing stability in a refrigerator at 4 ℃ in a dark place for a long time: the niclosamide is stored in a refrigerator at 4 ℃ for 6 months in a dark place, and the result of regular observation shows that the niclosamide has stable properties, no obvious color change and no precipitation. The oral liquid can be stored in refrigerator at-15 deg.C for 1 day, 7 days, 15 days, 1 month, 2 months, 3 months, 4 months, and 6 months without coagulation, freezing, or turbidity. Therefore, it is suitable for storage, transportation and use in cold seasons.

3 conclusion

The prepared niclosamide or salt oral liquid is placed at room temperature for one year without precipitation and floccules, and is placed at room temperature for 1 year in the dark, the content is reduced to less than 10 percent, and the stability is shown to be at least more than 1 year.

Example 3: a research on the dilution and standing stability of niclosamide or its salt oral liquid (5%) for livestock and poultry by mixing water, which comprises the following materials and method steps:

1 Material

1.1 test drugs: the oral liquid prepared according to the example 1 contains niclosamide with the mass percentage of 5%.

1.2 test materials: DHG-9140A type vacuum drying oven (shanghai yi constant laboratory instruments ltd); micropipettes (Eppendorf, Germany), ultrasonic washers (Shanghai, Inc.), pipettes, measuring cylinders, measuring cups, beakers, etc.

2 methods and results

The oral liquid prepared in example 1 was mixed with water in a recommended amount (250ppm, 10mL diluted to 2kg with tap water), 2 times the recommended amount (500ppm, 10mL diluted to 1kg with tap water), 4 times the recommended amount (1000ppm, 10mL diluted to 0.5kg with tap water), 10 times the recommended amount (2500ppm, 10mL diluted to 0.2kg with tap water), 20 times the recommended amount (5000ppm, 10mL diluted to 0.1kg with tap water), and the solution was observed for clarification and properties (color change, turbidity, precipitation, floc and floating) after standing for 4, 6, 8, 12 hours and 24 hours.

The results are shown in Table 2, and only after dilution with 10 times of recommended amount of mixed water for 24 hours and dilution with 20 times of recommended amount of mixed water for 12 and 24 hours, the solution becomes turbid and is in a uniform dispersion state, but no precipitate is separated out, and no floccules and particle floating substances are generated.

TABLE 2 stability after mixing of water of different concentrations over 24h

3 conclusion

The water is mixed according to the recommended concentration which is 1-20 times of the recommended dosage, and the solution is clear after the water is mixed, so that the requirements of clinical free medicine mixing and drinking and concentrated medicine mixing and drinking at different time can be met.

Example 4: a taenia test of niclosamide or salt oral liquid (5%) thereof for livestock and poultry, which uses the following materials and method steps:

1.1 materials

1.1 test drugs: the oral liquid prepared according to example 1, wherein the niclosamide content is 5% by mass.

Niclosamide tablets: each tablet is 0.5 g, each bottle is 100 tablets, and the tablet is produced by natural animal medicine company in Hanzhong.

1.2 test chickens: 15000 chicks of 17 days old bred by a certain farmer in Zhengzhou city are diagnosed to have cestodiasis according to epidemiology, clinical symptoms, pathological changes and fecal microscopic examination.

2 methods and results

From these 45 chickens were picked out and individually housed (feces with cestode segments and ova) for cachexia, feathers, emaciation, diarrhea, or bloody mucus. Groups were randomized and weighed and dosed 1 time according to table 1. The tablet is prepared by grinding, mixing with corn flour, making into pill, and orally taking by plug (group A), or orally injecting the oral liquid into injection (group B) with syringe without needle after diluting with tap water.

And (3) observation of curative effect: the clinical symptoms. After the administration, the patients were observed for three days, including the presence or absence of abnormality of spirit, appetite and drinking water. ② insect expelling situation: the test chickens are all raised in a single cage, full manure of 24h, 48h and 72h is collected one by one after dosing, and the worm bodies in the manure discharged by the chickens are washed by saline water (1% saline water) and examined under the microscope. C, autopsy: on the 5 th day of administration, the test chickens were individually examined by dissection, examined for parasites in the digestive tract by local helminthic dissection, and the anthelmintic rate was calculated. (see Table 3 below)

TABLE 3 insect repelling efficiency Observation

3 conclusion

A. B, C the anthelmintic rate of the three groups reaches 100%, the mental state returns to normal, the intestinal tract is not obviously changed by autopsy, the anthelmintic rate of the feeding group is 85%, and the two chickens still have mild enteritis in the next day of autopsy after the administration, which indicates that the curative effect of the mixed drinking medicine is higher than that of the mixed feeding and stirring material, and the reason may be that the oral liquid is dissolved after being mixed drinking and is more likely to enter the insect body. The dosage of the pesticide entering the body of the worm is faster and more, and in addition, the water drinking amount of the chicken is less influenced when the chicken suffers from tapeworm, the feed intake is obviously reduced, and the pesticide intake is less.

No side effect related to medication is found in the four medication groups, and the medicine is proved to be safe and quick to drink in a mixed mode, can be drunk in a mixed mode according to different proportions of water drinking all day long, can obtain higher intestinal medicine concentration, and is better in curative effect.

The feces of the control group without administration still have pregnant egg tablets, intestinal inflammation, poor appetite, low food intake and mucous stool with bloody discharge.

Different quantities of tapeworms are discharged successively from all the groups of herbs. Complete tapeworms or chain bodies and head knots are not found in intestinal tracts of groups A to C after the killing, 5 complete tapeworms are detected in two groups D only, which shows that the group A to C has 100% of insect expelling rate, and the chicken of the control group does not discharge tapeworms and only see pregnant egg nodules.

In conclusion, the invention provides a novel niclosamide preparation which can be orally taken by large animal individuals and can be taken by groups for veterinary clinic in the breeding industry, and experiments prove that: the preparation has stable property, no obvious content change (the content is reduced by less than 10%) after being placed at room temperature for one year, good drug effect and high safety, and has important application value in the field of veterinary drugs.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be able to cover the technical scope of the present invention by equivalent replacement or change according to the technical solution and the inventive concept of the present invention within the technical scope of the present invention.

Claims

1. The niclosamide or niclosamide salt oral liquid is characterized by comprising the following components in percentage by weight: 3-10% of niclosamide or salt thereof, 1-4% of surfactant, 20-70% of composite non-aqueous solvent, 0.02-0.5% of stabilizer, pH regulator for regulating pH to 8.0-9.0, and purified water with constant volume of 100%.

2. The niclosamide or salt thereof oral liquid of claim 1, wherein the salt is niclosamide ethanolamine, niclosamide piperazine, or niclosamide phosphate.

3. The niclosamide or salt oral liquid of claim 1, wherein the surfactant is one of sodium dodecyl sulfate, tween-80, tween-40, tween-20, peregal O, polyoxyethylene 40 stearate, poloxamer 188, maize 51, maize 52, and dioctyl sodium sulfa succinate.

4. The niclosamide or salt thereof oral liquid of claim 1, wherein the complex non-aqueous solvent is 2 to 3 combinations of ethanol, PEG400, α -pyrrolidone, glycerol formal, dimethylformamide, dimethylacetamide, DMSO, propylene glycol, glycerol; wherein when the composite non-aqueous solvent is 2 combinations, the ratio of the two is 5: 1-1: 5; when the composite non-aqueous solvent is 3 combinations, the ratio of the three is 4:1:1 to 1:4:1 to 1:1: 4.

5. The niclosamide or salt oral liquid according to claim 1, wherein the stabilizer is 2 combinations of EDTA-2Na, calcium sodium edetate, sodium tripolyphosphate, sodium sulfite, sodium formaldehyde-sulfoxylate, thiourea, and sodium thiosulfate.

6. The niclosamide or salt oral liquid of claim 1, wherein the pH adjuster is one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, meglumine, triethanolamine, ethanolamine, and ethylenediamine.

7. The preparation method of the niclosamide or the salt oral liquid thereof used by the livestock and the poultry as claimed in claim 1 is characterized in that the specific preparation process comprises the following steps:

step (2): dissolving the stabilizer in purified water, and uniformly stirring to obtain solution B;

and (3): dissolving a pH regulator in the purified water, and stirring and dissolving to obtain a solution C;

and (6): and E, filtering the solution E, subpackaging, sealing in a brown bottle, keeping out of the sun, and storing in shade.

8. The application of niclosamide or salt oral liquid thereof as claimed in claim 1, wherein the niclosamide or salt oral liquid thereof is applied to preparation of livestock and poultry tapeworm medicines.

9. The use of niclosamide or a salt thereof oral liquid according to claim 1, wherein the niclosamide or a salt thereof oral liquid is used for preparing molluscicidal drugs.

10. The use of niclosamide or a salt thereof oral liquid according to claim 1, wherein the niclosamide or a salt thereof oral liquid is used for preparing an anti-tumor and anti-viral drug.