CN112353774B - Nascitide flavor chewable tablet, preparation method thereof and application thereof to clostridium welchii disease of dog - Google Patents

Abstract

The invention discloses a nosiheptide flavor chewable tablet, a preparation method thereof and application thereof in dog clostridium welchii disease, wherein the formula comprises the following components: comprises the following components in percentage by mass: 1-10% of nosiheptide, 5% of an acidifier, 30-40% of a diluent, 1% of a binder, 30-40% of a filler, 2-10% of a disintegrant, 5-20% of a flavoring agent and 1-5% of a coating agent; the acidifying agent is added in the formula of the invention to prepare the acidic adhesive, so that the stability of the main component of the nosiheptide is greatly improved, the production of the nosiheptide chewable tablet with controllable quality is facilitated, and the effective period of the product can be obviously prolonged; according to the invention, a carboxymethyl ethyl cellulose aqueous system is used for coating, so that the solubility and bioavailability of nosiheptide are improved; animal experiments show that: the nosiheptide flavor chewable tablet produced by the invention can effectively treat clostridium welchii disease of dogs.

Description

Nascitide flavor chewable tablet, preparation method thereof and application thereof to clostridium welchii disease of dog

Technical Field

The invention relates to the field of medicines, in particular to a nosiheptide flavor chewable tablet, a preparation method thereof and application thereof to clostridium welchii disease of dogs.

Background

Clostridium welchii can appear in human and animal excreta, soil, water and dust, and belongs to typical conditioned pathogenic bacteria; most of the diseases are prevalent in late autumn and early winter, especially in conditions of abnormal climate change, overcast and rainy and humid conditions; the disease can be developed according to the age and sex. The clostridium welchii can infect various animals, such as dog acute enteritis, cattle enteritis, piglet necrotic enteritis, rabbit enteritis and the like, in recent years, domestic livestock mortality is often related to the bacteria, the disease is acute, the disease course is short, and sudden death is realized without any prophase symptoms, and the mortality rate is extremely high.

Acute death of dogs caused by clostridium welchii disease of dogs caused by clostridium welchii occurs at home and tends to rise. Due to the lack of understanding, there is a certain pressure on the prevention of diseases and the mind of workers.

The dog clostridium welchii disease is acute septicemia of dogs caused by clostridium welchii (also known as clostridium perfringens) and is characterized by multiple organ hemorrhage, edema, acute lesion and death of dogs. The main toxin secreted by the clostridium welchii is synthesized and can be divided into types A, B, C, D and E, wherein the type A can infect people to form emphysema gangrene. B. Type C, D is closely related to intestinal infections in animals. The infected dogs are mainly type A and type C.

The nosiheptide can effectively prevent and treat clostridium welchii disease of dogs, but for sick animals, the palatability problem of treatment medicines is very critical, because the medicines cannot be forcedly fed to increase the stress on the animals, the palatability of the medicines is poor, the treatment effect of the medicines can be directly influenced, and the treatment failure is caused.

In order to improve the palatability of the medicine, the existing dog medicine preparation is more prone to be prepared into flavor chewable tablets, the appearance and the smell of the chewable tablets are similar to those of meat foods, and the palatability of the medicine is greatly improved. But this makes the disintegration and dissolution of the tablet more difficult; most of flavoring agents added into the flavor chewable tablets in the prior art generally have great influence on the stability of main medicine components, and particularly, the nosiheptide serving as a fermentation antibiotic is easy to degrade after being stored in the environment for a long time, so that the problem of the stability of the nosiheptide chewable tablets is also very critical.

The invention needs a nosiheptide flavor chewable tablet which has good palatability, can quickly dissolve out active ingredients and has stable quality, and solves the problems.

Disclosure of Invention

In order to solve the defects of the prior art, the invention aims to provide a nosiheptide flavor chewable tablet, a preparation method thereof and application thereof to dog clostridial disease, and the nosiheptide flavor chewable tablet has the advantages of good palatability, small stimulation to animal gastrointestinal tract, rapid disintegration, rapid dissolution of effective components and stable quality.

In order to achieve the above object, the present invention adopts the following technical solutions:

a nosiheptide flavored chewable tablet, the formula comprises: comprises the following components in percentage by mass: 1-10% of nosiheptide, 5% of an acidifier, 30-40% of a diluent, 1% of a binder, 30-40% of a filler, 2-10% of a disintegrant, 5-20% of a flavoring agent and 1-5% of a coating agent.

The nosiheptide flavored chewable tablet comprises the following components in percentage by weight: citric acid, phosphoric acid, lactic acid, malic acid, benzoic acid.

In the nosiheptide flavored chewable tablet, the acidulant is citric acid and phosphoric acid; the weight ratio of the citric acid to the phosphoric acid is 1: 1.

The nosiheptide flavored chewable tablet comprises the following disintegrating agents: sodium carboxymethyl starch, crospovidone, and povidone.

The nosiheptide flavored chewable tablet of claim 1, the binder comprising: hydroxypropyl methyl cellulose, maltodextrin, cyclodextrin.

The nosiheptide flavored chewable tablet comprises the following coating agents: hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, polyacrylic resins, carboxymethyl ethylcellulose and crosslinked polyvinylpyrrolidone.

The nosiheptide flavored chewable tablet comprises the following flavoring agents: artificial chicken essence, artificial beef essence and yeast powder.

The application of the nosiheptide flavored chewable tablet is used for treating clostridium welchii disease of dogs.

A preparation method of a nosiheptide flavored chewable tablet comprises the following steps:

preparing materials according to a formula, wherein the formula comprises the following components in percentage by mass: 1-10% of nosiheptide, 5% of an acidifier, 30-40% of a diluent, 1% of a binder, 30-40% of a filler, 2-10% of a disintegrant, 5-20% of a flavoring agent and 1-5% of a coating agent;

step two, crushing nosiheptide, diluent, filler, disintegrant, adhesive and flavoring agent, and then respectively sieving and filtering;

mixing nosiheptide, a diluent and a disintegrating agent to obtain a mixture, preparing a binding agent and an acidifier together to obtain a binding liquid, mixing the mixture and the binding liquid to prepare a soft material, sieving the soft material to prepare granules, drying the granules at 40-45 ℃, and then sieving the granules to obtain finished granules;

step four, coating the whole granules with a coating agent, and then sieving the whole granules to obtain coated granules;

and step five, uniformly mixing the coated granules with a filling agent and a flavoring agent, and tabletting to obtain the nosiheptide flavor chewable tablets.

In the preparation method of the nosiheptide flavored chewable tablet, the coating is a fluidized bed coating.

The invention has the advantages that:

the acidifying agent is added in the formula of the invention to prepare the acidic adhesive, so that the stability of the main component of the nosiheptide is greatly improved, the production of the nosiheptide chewable tablet with controllable quality is facilitated, and the effective period of the product can be obviously prolonged;

according to the invention, the nosiheptide-containing raw material particles are coated, so that the irritation of bitter taste and mouthfeel during oral chewing can be effectively removed; the coating is carried out by using a carboxymethyl ethyl cellulose aqueous system, the coating is kept complete on the nosiheptide particles after the nosiheptide particles are normally chewed in the oral cavity and enter the stomach, and active ingredients are released only when the nosiheptide particles enter the intestinal tract environment, so that the solubility and the bioavailability of the nosiheptide are improved;

animal experiments show that: the nosiheptide flavor chewable tablet produced by the invention can effectively treat clostridium welchii disease of dogs;

the invention uses the artificial beef essence and the like as the flavoring agent, improves the palatability of the product and is convenient for clinical popularization;

the preparation process is simple and suitable for industrial production.

Detailed Description

The present invention will be described in detail with reference to the following embodiments.

A nosiheptide flavored chewable tablet, the formula comprises: comprises the following components in percentage by mass: 1-10% of nosiheptide, 5% of an acidifier, 30-40% of a diluent, 1% of a binder, 30-40% of a filler, 2-10% of a disintegrant, 5-20% of a flavoring agent and 1-5% of a coating agent.

The acidifying agent comprises: citric acid, phosphoric acid, lactic acid, malic acid, benzoic acid; as a preference, the acidulant is citric acid and phosphoric acid; the weight ratio of the citric acid to the phosphoric acid is 1: 1.

The diluent comprises: microcrystalline cellulose, starch glycoside, chitosan. Preferably, the diluent is microcrystalline cellulose.

The filler comprises: soybean protein powder, corn starch, wheat protein powder and corn flour. Preferably, the bulking agent is corn starch.

The disintegrating agent comprises: sodium carboxymethyl starch, crospovidone, and povidone. Preferably, the disintegrant is crospovidone.

The adhesive comprises: hydroxypropyl methyl cellulose, maltodextrin, cyclodextrin. As a preference, the binder is preferably hydroxypropylmethylcellulose.

The coating agent comprises: hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, polyacrylic resins, carboxymethyl ethylcellulose and crosslinked polyvinylpyrrolidone. Preferably, the coating agent is carboxymethyl ethyl cellulose.

The flavoring agent comprises: artificial chicken essence, artificial beef essence and yeast powder. Preferably, the flavoring agent is artificial beef flavor.

It should be noted that: the inclusion means that one or more of them are used in combination.

A preparation method of nosiheptide flavored chewable tablets comprises the following steps:

preparing materials according to a formula, wherein the formula comprises the following components in percentage by mass: 1-10% of nosiheptide, 5% of an acidifying agent, 30-40% of a diluent, 1% of a binder, 30-40% of a filler, 2-10% of a disintegrating agent, 5-20% of a flavoring agent and 1-5% of a coating agent;

step two, crushing nosiheptide, diluent, filler, disintegrant, adhesive and flavoring agent, and then respectively sieving and filtering; as a preference, the sieving is carried out by using a 80-mesh sieve.

Mixing nosiheptide, a diluent and a disintegrating agent to obtain a mixture, preparing a binding agent and an acidifier together to obtain a binding liquid, mixing the mixture and the binding liquid to prepare a soft material, sieving the soft material to prepare granules, drying the granules at 40-45 ℃, and then sieving the granules to obtain finished granules; preferably, the mixture is sieved by a 40-mesh sieve to prepare granules, and after the granules are dried at the temperature of 40-45 ℃, the granules are sieved by a 40-mesh sieve and a 65-mesh sieve to complete granules, and coarse granules and fine powder are removed.

Step four, coating the whole granules with a coating agent, and then sieving the whole granules to obtain coated granules; preferably, the coating process is carried out by fluidized bed coating, and preferably, the whole granules are sieved by 40 meshes and 65 meshes.

And step five, uniformly mixing the coated granules with a filling agent and a flavoring agent, and tabletting to obtain the nosiheptide flavor chewable tablets.

Samples were prepared for experimental validation as follows:

firstly, preparing a bonding liquid and a coating liquid for later use;

preparation of Binder A (for example, 1000 g of Natexide chewable tablet)

Weighing 250ml of purified water, adding 10g of hydroxypropyl methyl cellulose, uniformly stirring, adding 25 g of citric acid and 25 g of phosphoric acid, and fully and uniformly stirring to obtain the bonding liquid A for later use.

Preparation of Binder B (taking 1000 g of Natexide chewable tablet as an example)

Weighing 250ml of purified water, adding 10g of hydroxypropyl methyl cellulose, and uniformly stirring to obtain a bonding liquid B for later use.

3, preparation of coating solution

Preparing 100ml of 20% ethanol-water solution, adding 5g of carboxymethyl ethyl cellulose, and uniformly stirring to obtain the coating solution.

Example 1

This example prepares a nosiheptide flavored chewable tablet of the present invention, made from the following raw materials in mass percent as in table 1:

TABLE 1 Nateside-flavored chewable tablets of the invention and the Components and amounts thereof

The preparation method comprises the following steps: respectively sieving nosiheptide, microcrystalline cellulose, corn starch, cross-linked polyvinylpyrrolidone and artificial beef essence with a 80-mesh sieve, taking the screened nosiheptide, microcrystalline cellulose and cross-linked polyvinylpyrrolidone according to a proportion, uniformly mixing, adding the prepared bonding liquid A, preparing a soft material, sieving with a 40-mesh sieve for granulation, drying at 45 ℃, sieving with a 40-mesh sieve and a 65-mesh sieve for granulation, and removing coarse particles and fine powder to obtain granules; performing fluidized bed coating on the granules by using a coating solution prepared in advance, increasing the weight of the coating by 5%, then sieving by using a 40-mesh sieve and a 65-mesh sieve for grading, and removing coarse granules and fine powder to obtain coated granules; mixing the coated granule with corn starch and artificial beef essence, and tabletting.

Example 2

This example prepares the nosiheptide flavored chewable tablets of the invention, which are prepared from the following raw materials in mass percent as shown in table 2:

TABLE 2 Components and contents of the nosiheptide flavored chewable tablets of the invention

The preparation method comprises the following steps: respectively sieving nosiheptide, microcrystalline cellulose, corn starch, cross-linked polyvinylpyrrolidone and artificial beef essence with a 80-mesh sieve, taking the screened nosiheptide, microcrystalline cellulose and cross-linked polyvinylpyrrolidone according to a proportion, uniformly mixing, adding the prepared bonding liquid A, preparing a soft material, sieving with a 40-mesh sieve for granulation, drying at 45 ℃, sieving with a 40-mesh sieve and a 65-mesh sieve for granulation, and removing coarse particles and fine powder to obtain granules; coating the above granules with coating solution prepared in advance by fluidized bed, increasing the weight of the coating by 5%, sieving with 40 mesh and 65 mesh sieves, grading, and removing coarse granules and fine powder to obtain coated granules; mixing the coated granule with corn starch and artificial beef essence, and tabletting.

Example 3

In this example, the nosiheptide flavor chewable tablet of the invention is prepared from the following raw materials in percentage by mass as shown in table 3:

TABLE 3 Nascipeptide-flavored chewable tablets of the invention and the Components and amounts thereof

The preparation method comprises the following steps: respectively sieving nosiheptide, microcrystalline cellulose, corn starch, crosslinking polyvinylpyrrolidone and artificial beef essence with a 80-mesh sieve, taking the screened nosiheptide, microcrystalline cellulose and crosslinking polyvinylpyrrolidone according to a proportion, uniformly mixing, adding the prepared bonding liquid A, preparing a soft material, sieving with a 40-mesh sieve for granulation, drying at 45 ℃, sieving with a 40-mesh sieve and a 65-mesh sieve for granulation, and removing coarse particles and fine powder to obtain granules; coating the above granules with coating solution prepared in advance by fluidized bed, increasing the weight of the coating by 5%, sieving with 40 mesh and 65 mesh sieves, grading, and removing coarse granules and fine powder to obtain coated granules; mixing the coated granule with corn starch and artificial beef essence, and tabletting.

COMPARATIVE EXAMPLE 1 (without addition of acidifying agent)

In this example, the nosiheptide flavor chewable tablet of the invention is prepared from the following raw materials in mass percent as shown in table 4:

TABLE 4 Components and amounts of the Nosiheptide flavored chewable tablets of the present invention

The preparation method comprises the following steps: respectively sieving nosiheptide, microcrystalline cellulose, corn starch, cross-linked polyvinylpyrrolidone and artificial beef essence with a 80-mesh sieve, taking the screened nosiheptide, microcrystalline cellulose and cross-linked polyvinylpyrrolidone according to a proportion, uniformly mixing, adding the prepared bonding liquid B, preparing a soft material, sieving with a 40-mesh sieve for granulation, drying at 45 ℃, sieving with a 40-mesh sieve and a 65-mesh sieve for granulation, and removing coarse particles and fine powder to obtain granules; coating the above granules with coating solution prepared in advance by fluidized bed, increasing the weight of the coating by 5%, sieving with 40 mesh and 65 mesh sieves, grading, and removing coarse granules and fine powder to obtain coated granules; mixing the coated granule with corn starch and artificial beef essence, and tabletting.

Experiment one, the stability of the nosiheptide sugar-free chewable tablet is researched by using samples 1-3 and a comparison sample 1;

referring to the requirement of the appendix 9001 guiding principles of raw material drug and preparation stability test of the first part of the 2015 edition of the veterinary pharmacopoeia of the republic of China, the preparation is placed at 40 ℃ and 75% RH for 6 months to carry out an accelerated test, the property change of the preparation is observed, and the content and the change of related substances are measured by High Performance Liquid Chromatography (HPLC). Table 5 shows the results of accelerated tests of the formulations prepared in the respective examples.

TABLE 5 Nascitide flavor chewable tablet accelerated test results

As can be seen from the results in Table 5, when the samples 1 to 3 of the present invention were left at 40 ℃ and 75% relative humidity for 6 months, the properties were not significantly changed, and the content of the related substances were all within the control range; the nosiheptide chewable tablet prepared by the comparative example 1 without adding the acidulant has greatly increased related substances and obviously reduced content. Compared with the comparative example 1, the nosiheptide flavor chewable tablet prepared by the invention has the advantage that the preparation stability is obviously improved.

Experiment two, the external dissolution test of the nosiheptide flavor chewable tablet body is carried out;

dissolution assay of nosiheptide: according to the dissolution determination method (appendix XC of the year 2015 edition of Chinese pharmacopoeia) of the second method, 900ml of hydrochloric acid solution with pH1.0 and phosphate buffer solution with pH6.8 are respectively used as two dissolution media, the rotating speed is 75 r/min, and the result is shown in the table 6.

TABLE 6 dissolution test results of nosiheptide flavored chewable tablets

The dissolution tests described above were performed in a hydrochloric acid solution at a pH of 1.0 to simulate the gastric environment and a phosphate buffered saline solution at a pH of 6.8 to simulate the intestinal environment, respectively.

As can be seen from Table 6, the nosiheptide flavor chewable tablet prepared by the invention is not easy to dissolve in a simulated stomach environment, the dissolution rate in 30min is between 8.6% and 10.4%, and the dissolution rate in a simulated intestinal environment can reach more than 95%, which shows that the nosiheptide flavor chewable tablet prepared by the invention is not neutralized by gastric acid after being orally taken into the stomach, most of the active ingredients are released after the active ingredients reach the intestinal tract, the dissolution rate of the prepared nosiheptide flavor chewable tablet in the intestinal tract is high, and the dissolution rate is more than 90% in 30min, so that the dissolution requirement of the nosiheptide chewable tablet is met.

Experiment III, the treatment effect of the nosiheptide on the artificial infection of the clostridium welchii of the Chinese rural dogs is tested;

1. test materials

Test bacteria: clostridium welchii type a, separation of dogs dying of illness in canine farms.

Test animals: chinese garden dog 4 months old, from Zhejiang certain dog farm

Test drugs: the nosiheptide flavored chewable tablets were prepared according to the procedure of example 4.

Metronidazole tablets purchased from drugstore

2. Test method

Design of experiments

The attacking dose of about 80 percent of the attacking dogs with clinical symptoms of the clostridium welchii is taken as the selection standard of the attacking dose in the formal test. Determining the amount of challenge bacteria to be 1 × 10 ⁸ CFU/mL, 20mL per dog for challenge.

According to the requirements in the "clinical efficacy evaluation test guiding principles of antibacterial drugs II and III stage", 20 healthy Chinese rural dogs in each group were treated with a high, medium and low dosage levels of nosiheptide chewable tablets, a metronidazole control group (positive control group), an infection non-administration control group (model control group) and a non-infection non-administration group (blank control group). The specific groupings are shown in Table 7.

Table 7 test grouping and dosing treatment

Administration therapy, administration mode

The administration persons were divided and treated according to the official test animal administration table (table 7), the administration group was self-challenged for 6 hours, and after clinical symptoms appeared in test dogs, administration was started for 5 days 2 times a day, and the administration dose was shown in table 7.

Pharmacodynamic evaluation index

The clinical performances of the groups before the administration period, 5d after the administration, 1 st day, 3 rd day, 5 th day and 7 th day after the withdrawal of the drug are recorded in detail, the clinical indexes are comprehensively graded, the drug effect is evaluated according to the following parameters, and the curative effect is judged according to the values.

Mortality rate: typical symptoms of clostridium welchii disease appear and die during the test, dogs with typical characteristic lesions are dissected, and clostridium welchii is separated from the intestinal tract, and is judged to be infected and die. The mortality rate was calculated from the number of deaths of each group of animals, and the mortality rate was determined as the number of dead dogs/number of test dogs

Cure rate

During the test period, clinical symptoms disappear after the drug is taken, the spirit, the appetite and the like are recovered to be normal, and the dogs gaining weight close to or exceeding the healthy control group are judged to be cured. And calculating the cure rate according to the cure number of each group of animals, wherein the cure rate is the number of cured dogs/the number of test dogs.

The effective rate is as follows: the cured dogs and the dogs infected with the drugs, which have obviously reduced or disappeared clinical symptoms such as reduced appetite, diarrhea and the like compared with those infected with the control group, are judged to be effective. The effective rate was calculated from the number of animals per group (number of cured dogs + number of therapeutically effective dogs)/number of test dogs.

Third, results and analysis

Clinical symptoms

The drug-free dog is not infected, and in the initial stage, the sick dog is in depression and has normal appetite. The dog is found to have the phenomena of messy rush, collision and circling in the morning, part of the dog only falls down quickly, muscles of the whole body tremble, twitch, limb movement, strange calling, groaning, offal and difficult breathing, the dog dies after a few minutes, the administration group has obviously reduced conditions, the sick dog has slight depression, most of the dogs have good prognosis and die occasionally.

Evaluation of clinical efficacy

The number of dead animals in 6 groups of dogs during the randomized control treatment trial was counted. No dogs died in the blank group, 16 dogs died in the infection-free group, 8 dogs died in the metronidazole control group, 6 dogs in the nosiheptide low dose group, 1 dog in the medium dose group, and 2 dogs in the high dose group. Compared with a negative control group, the mortality rate of animals in the positive drug control group, the nosiheptide high-dose group and the nosiheptide medium-dose group is remarkably reduced. The cure rates for each group were ranked, as can be seen: the nosiheptide high-dose group > nosiheptide middle-dose group > nosiheptide low-dose group > metronidazole group. See table 8 for details.

TABLE 8 therapeutic Effect of nosiheptide on necrotic enteritis in dogs

Conclusion

The test result shows that: the nosiheptide flavor chewable tablet prepared by the invention can effectively treat clostridium welchii disease of dogs, and the effect is superior to that of the traditional medicine metronidazole. Administration dose: canine, oral, 20mg/kg BW, 2 times daily for five days.

Fourth, the effect of the nosiheptide chewable tablet on preventing and treating the clostridium welchii disease of dogs is tested.

Onset of disease

A certain working dog farm in Zhejiang province is herded in a colony house with 15 dogs of 5 months of age, wherein 5 severe dogs die suddenly. The whole process from morbidity to mortality is about 12 hours. Food poisoning, raticide poisoning and other factors are excluded by epidemiological investigation, and the primary diagnosis of the resident veterinarian is suspected to be clostridium welchii infection.

Clinical symptoms

The severe acute dog has the symptoms of mental depression at the initial stage of disease incidence, anorexia, sudden stop of food intake within 6 to 12 hours, random flushing and collision, snaking towards the sky, circling, groaning, white foam in the mouth, dyspnea, incontinence of feces and urine, general muscle tremor, convulsion, limb movement and death after a few hours. The mild dog can only see that the dog has a depressed spirit, some dogs have obvious expansion of the abdomen, and the tip of the ear and the visible mucous membrane are cyanotic.

Laboratory diagnostics

The stomach, intestinal contents, heart blood, heart, liver, spleen, lung, kidney, muscle tissue and excrement samples of the dead dogs in the canine farm are collected and detected by laboratory bacteria separation identification, animal inoculation, serological identification and the like, so that the infection of the A-type clostridium welchii is confirmed.

Prevention and treatment measures

The dog house and the house of dead dogs were immediately blocked. Digging a pit with the depth of more than 2m, spreading quicklime, and burning dead dog bodies, garbage and foodstuff to be buried deeply. Soaking and cleaning and sterilizing the feeding apparatus with 0.2% peroxyacetic acid solution, and spraying 0.5% peroxyacetic acid solution to sterilize the ground, walls, ceiling and environment outside the colony house.

The samples 2, 3 and 4 were orally administered to the mild disease dogs in the farm, as well as to other asymptomatic dogs, at 20mg/kg BW, 2 times per day for 5 days in succession. By adopting the measures, the symptoms of 8 mild disease dogs in the canine farm gradually disappear, the dogs gradually recover to be normal on the 6 th to 10 th days after administration, no mild disease is converted into severe dogs, and no new cases occur so far.

The nosiheptide flavor chewable tablet has good palatability when being eaten, has small stimulation to the intestines and the stomach of animals, can be quickly disintegrated and quickly dissolve out effective components, and has stable quality; has effective treatment application on the dog welchiosis.

The foregoing illustrates and describes the principles, general features, and advantages of the present invention. It should be understood by those skilled in the art that the above embodiments do not limit the present invention in any way, and all technical solutions obtained by using equivalents or equivalent changes fall within the protection scope of the present invention.

Claims (9)

1. A nosiheptide flavored chewable tablet, the formulation comprising: comprises the following components in percentage by mass: 1-10% of nosiheptide, 5% of an acidifying agent, 30-40% of a diluent, 1% of a binder, 30-40% of a filler, 2-10% of a disintegrating agent, 5-20% of a flavoring agent and 1-5% of a coating agent.

2. A nosiheptide flavored chewable tablet according to claim 1, characterised in that the acidifying agent is: one or more of citric acid, phosphoric acid, lactic acid, malic acid and benzoic acid.

3. A nosiheptide flavored chewable tablet according to claim 2, characterised in that the acidulant is citric acid and phosphoric acid; the weight ratio of the citric acid to the phosphoric acid is 1: 1.

4. A nosiheptide flavored chewable tablet according to claim 1, characterised in that the disintegrant is: one or more of sodium carboxymethyl starch, crosslinked polyvinylpyrrolidone and polyvidone.

5. A nosiheptide flavored chewable tablet according to claim 1, characterized in that said binder is: hydroxypropyl methyl cellulose, maltodextrin, and cyclodextrin.

6. A nosiheptide flavored chewable tablet according to claim 1, characterised in that the coating agent is: hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, polyacrylic resin, carboxymethyl ethyl cellulose, and crosslinked polyvinylpyrrolidone.

7. An nosiheptide flavored chewable tablet according to claim 1, wherein the flavoring agent comprises: one or more of artificial chicken essence, artificial beef essence and yeast powder.

8. A preparation method of a nosiheptide flavored chewable tablet is characterized by comprising the following steps:

preparing materials according to a formula, wherein the formula comprises the following components in percentage by mass: 1-10% of nosiheptide, 5% of an acidifier, 30-40% of a diluent, 1% of a binder, 30-40% of a filler, 2-10% of a disintegrant, 5-20% of a flavoring agent and 1-5% of a coating agent;

step two, crushing nosiheptide, diluent, filler, disintegrant, adhesive and flavoring agent, and then respectively sieving and filtering;

mixing nosiheptide, a diluent and a disintegrating agent to obtain a mixture, preparing a binding agent and an acidifier together to obtain a binding liquid, mixing the mixture and the binding liquid to prepare a soft material, sieving the soft material to prepare granules, drying the granules at 40-45 ℃, and then sieving the granules to obtain finished granules;

step four, coating the whole granules with a coating agent, and then sieving the whole granules to obtain coated granules;

and step five, uniformly mixing the coated granules with a filling agent and a flavoring agent, and tabletting to obtain the nosiheptide flavor chewable tablets.

9. The process of claim 8, wherein said coating is a fluidized bed coating.