Parasite expelling medicine based on milbemycin oxime praziquantel and application of parasite expelling medicine

Abstract

The invention provides a parasite expelling drug based on milbemycin oxime praziquantel, and the parasite expelling drug comprises the following components in parts by mass: 10-30 parts of modified milbemycin oxime, 20-50 parts of nano-coated praziquantel, 5-15 parts of a compound synergist, 3-8 parts of a flavoring agent, and 2-5 parts of a disintegrating agent. According to the application of the parasite expelling medicine based on milbemycin oxime praziquantel, the medicine is used for preparing a preparation for preventing or treating mixed parasite infection of dogs and cats, and parasites comprise tapeworms, nematodes, flukes and vermiform mites. Through integrated innovation of chemical modification (succinylated milbemycin oxime), a nanotechnology (HPMC-coated praziquantel) and compounding cooperation (febantel-beta cyclodextrin), the comprehensive advantages of broad-spectrum parasite expelling, long-acting stability, safety and low toxicity are achieved, meanwhile, the problems that in the prior art, palatability is poor, the metabolic burden is high, and environmental adaptability is weak are solved, and the application has good application prospects. The composition is suitable for preventing and treating mixed parasite infection of dogs and cats.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to a parasite expelling drug based on milbemycin oxime and praziquantel and its application. Background Art

[0002] Parasite infection is a common health problem in pets (dogs, cats) and animal husbandry. Especially in hot and humid environments, the breeding of parasites such as tapeworms, nematodes, trematodes, and demodex mites can cause malnutrition, anemia, and even death in animals. Existing anthelmintic drugs are mostly based on a single active ingredient (such as milbemycin oxime, praziquantel) or simple compounding (such as milbemycin oxime + praziquantel), but there are still the following defects: 1. Limited anthelmintic spectrum: The existing compound drugs are insufficient in the treatment of mixed infections of trematodes, tapeworms, nematodes, etc., and especially have a low killing efficiency against drug-resistant worms (such as heartworm larvae).

[0003] 2. Poor stability: Milbemycin oxime is easily degraded under the influence of light, heat, and humid environments, resulting in a short drug storage period; praziquantel has a significant first-pass effect and low bioavailability (only about 80%).

[0004] 3. Poor palatability: Traditional tablets cause pets to refuse to eat due to bitterness, and forced feeding is required, which affects the medication compliance.

[0005] 4. Insufficient safety: Sensitive breeds such as collie dogs are prone to neurotoxic reactions (such as tremors, ataxia).

[0006] The existing technology improves palatability and anthelmintic spectrum by adjusting excipients (such as coating technology) or compounding with other anthelmintic ingredients (such as moxidectin). The coating technology (such as using hydroxypropyl methylcellulose or ethylcellulose) can cover the bitterness of the drug through physical isolation to improve palatability, but the hydrophobicity of the coating material may hinder the disintegration and dissolution of the drug in the digestive tract. For example, excessive coating will delay the release rate of active ingredients (such as milbemycin oxime, febantel), resulting in a decrease in the bioavailability of the drug at the target absorption site (such as the intestine); if the coating is too thin, the drug may be degraded in advance due to the action of gastric acid or digestive enzymes, affecting stability. In addition, some anthelmintic drugs (such as praziquantel) are sensitive to light and heat, and the existing coating technology is difficult to provide sufficient protection in complex environments (such as high-temperature transportation or long-term storage), resulting in a loss of potency. Compounding with broad-spectrum anthelmintic drugs such as moxidectin can expand the anthelmintic spectrum (such as covering nematodes and arthropods at the same time), but the combined use of multiple components will increase the metabolic pressure on the liver and kidneys, and still cannot solve the contradiction between drug stability and bioavailability, and the compounded ingredients may increase the metabolic burden on the liver and kidneys.

[0007] Therefore, it is necessary to design a parasite expelling drug based on milbemycin oxime and praziquantel and its application. Summary of the Invention

[0008] In order to overcome the deficiencies in the prior art, a parasitic expulsion drug based on milbemycin praziquantel and its application are provided.

[0009] In order to achieve the above object, the present invention provides the following technical solutions: A parasitic expulsion drug based on milbemycin praziquantel, calculated by mass, the drug comprises the following components: 10-30 parts of modified milbemycin, 20-50 parts of nano-coated praziquantel, 5-15 parts of compound synergist, 3-8 parts of flavoring agent, and 2-5 parts of disintegrant.

[0010] The preparation method of the succinylated milbemycin comprises the following steps: a. Dissolve milbemycin in acetone, add succinic anhydride with a molar ratio of 1:1.2, and react at 60 °C for 4 hours; b. Remove the solvent by vacuum distillation, and recrystallize the product with ethanol to obtain succinylated milbemycin; c. Mix succinylated milbemycin and polyvinylpyrrolidone in a mass ratio of 1:3, and spray-dry to obtain microspheres, which are the modified milbemycin.

[0011] The succinylation substitution degree of the modified milbemycin is 0.8-1.2, and the melting point is 180-185 °C.

[0012] The compound synergist is composed of febantel and β-cyclodextrin inclusion, and the molar ratio of febantel to β-cyclodextrin is 1:2.

[0013] The coating thickness of the nano-coated praziquantel is 10-50 nm, and the encapsulation efficiency ≥ 90%.

[0014] The particle size of the nano-coated praziquantel is 50-200 nm, and the coating material is hydroxypropyl methylcellulose.

[0015] The flavoring agent is natural chicken powder.

[0016] The disintegrant is cross-linked carboxymethyl cellulose sodium.

[0017] Application of a parasitic expulsion drug based on milbemycin praziquantel, the drug is used to prepare a preparation for preventing or treating mixed parasitic infections in dogs and cats, and the parasites include tapeworms, nematodes, trematodes and demodex mites.

[0018] The preparation includes tablets, and an ethylcellulose isolation layer is sprayed on the surface of the tablets, with a thickness of 10-20 μm.

[0019] Compared with the prior art, the advantages and beneficial effects of the present invention are: 1. Through the organic combination of molecular modification, dosage form innovation, and compounding strategies, this application not only solves the problems of narrow anthelmintic spectrum, drug resistance, and metabolic burden existing in traditional anthelmintics, but also achieves breakthroughs in palatability and environmental adaptability, providing an efficient, safe, and user-friendly solution for the prevention and treatment of mixed parasitic infections in dogs and cats.

[0020] 2. Enhancement of broad-spectrum anthelmintic efficacy: By succinylating milbemycin oxime, its targeting effect on drug-resistant Dirofilaria immitis larvae is enhanced. The succinyl group improves the inhibitory efficiency by 20% by enhancing the binding force between the drug and the parasite glutamate chloride channel, and has a more efficient killing ability especially for nematodes (such as hookworms and roundworms) and ectoparasitic mites (such as Demodex mites and Sarcoptes scabiei) in ivermectin-sensitive dog breeds. At the same time, the inclusion complex of febantel and β-cyclodextrin is compounded, which not only expands the coverage of intestinal protozoa (such as coccidia and trichomonas), but also makes up for the killing blind spots of traditional regimens for whipworms and trematodes through synergistic effects.

[0021] 3. Optimization of drug stability and release kinetics: The nano-coating technology significantly improves the physicochemical properties of praziquantel. The 10 - 50 nm nano-coating layer formed by hydroxypropyl methylcellulose (HPMC) can not only protect praziquantel from degradation by gastric acid, but also achieve targeted slow release in the intestine, increasing its peak plasma concentration (Cmax) to 1.5 times that of traditional preparations and extending the half-life to 4 - 6 hours. The process of combining succinylated milbemycin oxime with polyvinylpyrrolidone (PVP) microspheres significantly enhances the photothermal stability of the drug under high temperatures (such as storage conditions in tropical regions). After 36 months of storage, the degradation rate is ≤5%, and the bioavailability remains above 95%.

[0022] 4. Breakthrough in metabolic safety: Through the inclusion of febantel and β-cyclodextrin at a molar ratio of 1:2, the direct stimulation of free drug on liver metabolic enzymes (such as CYP450) is significantly reduced: Reduction of liver and kidney burden: The first-pass effect of febantel after inclusion is reduced by 30%, and the half-life is extended to 8 - 12 hours, reducing the frequency of repeated dosing. Side effect control: The molecular encapsulation effect of β-cyclodextrin enables febantel to be released at a fixed point in the intestine, reducing the systemic exposure. Clinical trials show that the incidence of gastrointestinal adverse reactions such as vomiting and diarrhea decreases by 50%.

[0023] 5. Improvement of palatability and medication compliance: This application adopts the spraying process of ethylcellulose isolation layer (10 - 20 μm), effectively blocking the spillage of the bitter taste of the drug, and making the palatability score reach 4.8 / 5 (the traditional tablet is 3.2 / 5). Combined with natural chicken powder flavoring agent, it further increases the willingness of dogs and cats to eat independently. In addition, croscarmellose sodium is used as a disintegrant to ensure that the tablet disintegrates quickly in the stomach (completely dispersed within 3 minutes), avoiding food refusal behavior caused by drug retention.

[0024] 6. Through the integrated innovation of chemical modification (succinylated milbemycin), nanotechnology (HPMC-coated praziquantel), and compound synergy (febantel-β-cyclodextrin), this application realizes the comprehensive advantages of broad-spectrum anthelmintic, long-term stability, and safety with low toxicity. At the same time, it solves the pain points such as poor palatability, high metabolic burden, and weak environmental adaptability in the existing technology, and is applicable to the prevention and treatment of mixed parasitic infections in dogs and cats. Detailed Embodiments

[0025] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0026] In this application, the models of various raw materials are briefly described as follows: Milbemycin Oxime: Purchased from Hubei Weishi Chemical Reagent Co., Ltd. (Hubei, China), model HBW-19 (export standard).

[0027] Praziquantel: Purchased from Zhejiang Hisun Pharmaceutical Co., Ltd. (Zhejiang, China), model CP2015 / USP42 (pharmaceutical grade).

[0028] Hydroxypropylmethylcellulose (HPMC): Purchased from Ashland Inc. (USA), model E5 LV (low-viscosity coating material).

[0029] β-Cyclodextrin (β-CD): Purchased from Roquette (France), model food grade (purity ≥ 99%).

[0030] Febantel: Purchased from Sigma-Aldrich (USA), model pharmaceutical grade (purity ≥ 98%).

[0031] Ethylcellulose (EC): Purchased from Dow Chemical Co. (USA), model Ethocel™ Standard 7FP (coating isolation layer).

[0032] Sodium carboxymethylcellulose cross-linked (CCMC-Na): Purchased from FMC Corporation (USA), model Ac-Di-Sol® (disintegrant).

[0033] Natural chicken powder: Purchased from Kerry Group (Ireland), model food grade flavoring agent.

[0034] Polyvinylpyrrolidone (PVP): Purchased from BASF, model K30.

[0035] A parasitic expelling drug based on milbemycin praziquantel, calculated by mass, the drug comprises the following components: 10-30 parts of modified milbemycin, 20-50 parts of nano-coated praziquantel, 5-15 parts of compound synergist, 3-8 parts of flavoring agent, and 2-5 parts of disintegrant.

[0036] The preparation method of the succinylated milbemycin comprises the following steps: a. Dissolve milbemycin in acetone, add succinic anhydride with a molar ratio of 1:1.2, and react at 60 °C for 4 hours; b. Remove the solvent by vacuum distillation, and recrystallize the product with ethanol to obtain succinylated milbemycin; c. Mix succinylated milbemycin and polyvinylpyrrolidone in a mass ratio of 1:3, and spray-dry to obtain microspheres, which are the modified milbemycin.

[0037] The succinylation substitution degree of the modified milbemycin is 0.8-1.2, and the melting point is 180-185 °C.

[0038] The compound synergist is composed of febantel and β-cyclodextrin inclusion, and the molar ratio of febantel to β-cyclodextrin is 1:2.

[0039] The coating thickness of the nano-coated praziquantel is 10-50 nm, and the encapsulation efficiency is ≥90%.

[0040] The particle size of the nano-coated praziquantel is 50-200 nm, and the coating material is hydroxypropyl methylcellulose.

[0041] The flavoring agent is natural chicken powder.

[0042] The disintegrant is croscarmellose sodium.

[0043] Application of a parasitic expelling drug based on milbemycin praziquantel, the drug is used for preparing a preparation for preventing or treating mixed parasitic infections of dogs and cats, and the parasites include tapeworms, nematodes, trematodes and demodex mites.

[0044] The preparation includes tablets, and an ethylcellulose isolation layer is sprayed on the surface of the tablets, with a thickness of 10-20 μm.

[0045] In practical applications, the dosing dose of this application is 0.5-2 mg / kg body weight, once a week for three consecutive weeks. After storage at below 25 °C for 36 months, the degradation rate of milbemycin is ≤5%, and the bioavailability of praziquantel is ≥95%. Compared with the free form of febantel, its hepatic first-pass effect is reduced by 30%, and the half-life is extended to 8-12 hours.

[0046] The present application will be further described below in conjunction with specific examples and analytical tests: Example 1 The antiparasitic drug based on milbemycin praziquantel, in parts by mass, the drug comprises the following components: 20 parts of modified milbemycin, 35 parts of nano-coated praziquantel, 10 parts of compound synergist, 5 parts of flavoring agent, and 3 parts of disintegrant.

[0047] The succinylation substitution degree of the modified milbemycin is 1.

[0048] The compound synergist is composed of febantel and β-cyclodextrin inclusion, and the molar ratio of febantel to β-cyclodextrin is 1:2.

[0049] The coating thickness of the nano-coated praziquantel is 30 nm, and the encapsulation efficiency ≥ 90%.

[0050] The particle size of the nano-coated praziquantel is 100 nm, and the coating material is hydroxypropyl methylcellulose.

[0051] The flavoring agent is natural chicken powder.

[0052] The disintegrant is cross-linked carboxymethyl cellulose sodium.

[0053] The application of the antiparasitic drug based on milbemycin praziquantel, the drug is used to prepare a preparation for preventing or treating mixed parasite infections of dogs and cats, and the parasites include tapeworms, nematodes, trematodes and demodex mites.

[0054] The preparation includes tablets, and an ethylcellulose isolation layer is sprayed on the surface of the tablets, with a thickness of 15 μm.

[0055] Example 2 The antiparasitic drug based on milbemycin praziquantel, in parts by mass, the drug comprises the following components: 25 parts of modified milbemycin, 40 parts of nano-coated praziquantel, 12 parts of compound synergist, 6 parts of flavoring agent, and 4 parts of disintegrant.

[0056] The succinylation substitution degree of the modified milbemycin is 1.2.

[0057] The compound synergist is composed of febantel and β-cyclodextrin inclusion, and the molar ratio of febantel to β-cyclodextrin is 1:2.

[0058] The coating thickness of the nano-coated praziquantel is 30 nm, and the encapsulation efficiency ≥ 90%.

[0059] The particle size of the nano-coated praziquantel is 100 nm, and the coating material is hydroxypropyl methylcellulose.

[0060] The flavoring agent is natural chicken powder.

[0061] The disintegrant is croscarmellose sodium.

[0062] Use of a parasite expelling drug based on milbemycin praziquantel, said drug for preparing a preparation for preventing or treating mixed parasite infections in dogs and cats, said parasites including tapeworms, nematodes, trematodes and demodex mites.

[0063] The preparation includes tablets, and an ethylcellulose isolation layer is sprayed on the surface of the tablets, with a thickness of 10 μm.

[0064] Example 3 A parasite expelling drug based on milbemycin praziquantel, by mass, said drug includes the following components: 15 parts of modified milbemycin, 30 parts of nano-coated praziquantel, 8 parts of a compound synergist, 4 parts of a flavoring agent, 2 parts of a disintegrant.

[0065] The degree of succinylation substitution of the modified milbemycin is 0.8.

[0066] The compound synergist is composed of febantel and β-cyclodextrin inclusion, and the molar ratio of febantel to β-cyclodextrin is 1:2.

[0067] The coating thickness of the nano-coated praziquantel is 30 nm, and the encapsulation efficiency ≥90%.

[0068] The particle size of the nano-coated praziquantel is 100 nm, and the coating material is hydroxypropyl methylcellulose.

[0069] The flavoring agent is natural chicken powder.

[0070] The disintegrant is croscarmellose sodium.

[0071] Use of a parasite expelling drug based on milbemycin praziquantel, said drug for preparing a preparation for preventing or treating mixed parasite infections in dogs and cats, said parasites including tapeworms, nematodes, trematodes and demodex mites.

[0072] The preparation includes tablets, and an ethylcellulose isolation layer is sprayed on the surface of the tablets, with a thickness of 20 μm.

[0073] Comparative Example 1 In this comparative example, the same parts as in Example 1 will not be elaborated, and the differences are as follows: Ordinary milbemycin is used instead of modified milbemycin. Ordinary uncoated praziquantel is used instead of nano-coated praziquantel. It does not contain a compound synergist.

[0074] Comparative Example 2 In this comparative example, the same parts as in Example 1 will not be elaborated, and the differences are as follows: Febantel is not included in β-cyclodextrin. Praziquantel is coated with ordinary ethylcellulose coating (50 μm).

[0075] Comparative Example 3 In this comparative example, the same parts as in Example 1 will not be elaborated, and the differences are described as follows: Gelatin is used to replace HPMC for coating praziquantel.

[0076] Comparative Example 4 In this comparative example, the same parts as in Example 1 will not be elaborated, and the differences are described as follows: In the compound synergist, febantel / β-cyclodextrin = 1:1.

[0077] Comparative Example 5 In this comparative example, the same parts as in Example 1 will not be elaborated, and the differences are described as follows: There is no ethylcellulose isolation layer, and the chicken powder flavoring agent is directly added.

[0078] Test methods and result analysis The following 5 indicators are tested for the above groups: 1. Deworming efficiency (in vitro culture experiment) Method: Select Dirofilaria immitis (drug-resistant strain L3 larvae), Ancylostoma caninum (adult worms), Taenia taeniaeformis (gravid segments), and Demodex canis (adult worms) to establish an in vitro culture model, and add media containing the drugs of each example / comparative example (concentration 0.1 mg / mL) respectively. Calculate the mortality rate after 24 hours. The specific results are shown in Table 1.

[0079] As can be seen from Table 1, due to the targeting enhancement effect of succinylated milbemycin and the sustained-release characteristics of HPMC nano-coating in the three example groups, the killing efficiency of drug-resistant Dirofilaria immitis larvae is significantly higher than that of the comparative examples (the lack of binding force in Comparative Example 1 due to no modification).

[0080] In Comparative Example 2, due to the lack of inclusion of the synergist, the rapid release of febantel leads to a reduction in the synergistic effect, and the mortality rate of tapeworms is only 78.4%; while in Comparative Example 3, the praziquantel coated with gelatin has a serious degradation in gastric acid, and the deworming efficiency drops by more than 15%.

[0081] Table 1 Deworming efficiency results

[0082] 2. High humidity stability (accelerated experiment) Method: Place the samples in an environment of 40 °C / 75% RH for 6 months, and detect the residual rates of milbemycin and praziquantel (HPLC method). The specific results are shown in Table 2.

[0083] Table 2 High humidity stability results

[0084] As can be seen from Table 2, the HPMC nano-coating layer in the example group effectively blocked the degradation of praziquantel in the damp and hot environment (residual rate > 95%), while the gelatin coating in Comparative Example 3 led to a 34.6% degradation of praziquantel due to high hygroscopicity. In Comparative Example 5, the ethylcellulose isolation layer was not used, and milbemycin was partially degraded by light (residual rate 93.6%), which was lower than that in the example group.

[0085] 3. Bioavailability (Canine Plasma Pharmacokinetics) Method: Beagle dogs were orally administered 20 mg / kg once, and the blood drug concentration (LC-MS / MS) was detected to calculate Cmax (peak concentration) and T1 / 2 (half-life).

[0086] Table 3 Bioavailability Test Results

[0087] As can be seen from Table 3, the succinylated milbemycin combined with PVP microsphere process in Example 1 increased Cmax to 1.7 times that of the traditional preparation (Comparative Example 1), and the half-life was extended by nearly 2 times. In Comparative Example 3, the premature release of praziquantel coated with gelatin in gastric acid led to a 45% decrease in Cmax.

[0088] 4. Palatability Test (Voluntary Feed Intake Rate) Method: 100 dogs / cats were randomly grouped, provided with medicated food, and the first voluntary feeding rate (within 10 minutes) was recorded. The test results of the voluntary feed intake rate are shown in Table 4.

[0089] Table 4 Test Results of Voluntary Feed Intake Rate

[0090] As can be seen from Table 4, the ethylcellulose isolation layer (15 μm) in Example 1 effectively masked the bitter taste, and combined with natural chicken powder, the voluntary feed intake rate of dogs reached 94%; while in Comparative Example 1, uncoated tablets led to poor palatability (feed intake rate was only 62%).

[0091] 5. Safety (Adverse Reaction Rate) Method: Clinical trials (200 infected dogs) were conducted to record the incidence of vomiting, diarrhea, and neurological symptoms. The test results of the adverse reaction rate are shown in Table 5.

[0092] Table 5 Test Results of Adverse Reaction Rate

[0093] As can be seen from Table 5, the febantel-β-cyclodextrin inclusion complex (1:2) in Example 1 reduces the gastrointestinal irritation of the free drug, and the vomiting rate decreases by 75% compared with Comparative Example 2. In Comparative Example 4, due to improper inclusion ratio (1:1), the insufficient release of febantel leads to an increase in adverse reactions.

[0094] Through the comparative tests of the examples and comparative examples, the technical solution of the present invention is significantly superior to the traditional process in terms of anthelmintic spectrum, stability, bioavailability and safety. In particular, the killing efficiency against drug-resistant parasites is increased by more than 20%, the high-temperature storage stability breaks through the industry standard (degradation rate < 5%), and the improved palatability enables the self-feeding rate of pets to exceed 90%. This invention provides an efficient, safe and user-friendly solution for mixed parasite infections in dogs and cats.

[0095] The above are the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle described in the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A parasitic expulsion drug based on milbemycin praziquantel, characterized in that, The drug comprises the following components in parts by mass: 10 - 30 parts of modified milbemycin, 20 - 50 parts of nano - coated praziquantel, 5 - 15 parts of compound synergist, 3 - 8 parts of flavoring agent, and 2 - 5 parts of disintegrant.

2. The antiparasitic drug based on milbemycin praziquantel according to claim 1, characterized in that, The preparation method of the succinylated milbemycin comprises the following steps: a. Dissolve milbemycin in acetone, add succinic anhydride with a molar ratio of 1:1.2, and react at 60 °C for 4 hours; b. Remove the solvent by vacuum distillation, and recrystallize the product with ethanol to obtain succinylated milbemycin; c. Mix succinylated milbemycin and polyvinylpyrrolidone in a mass ratio of 1:3, and spray - dry to obtain microspheres, which are the modified milbemycin.

3. The parasitic expulsion drug based on milbemycin praziquantel according to claim 1, characterized in that: The succinylation substitution degree of the modified milbemycin is 0.8 - 1.2, and the melting point is 180 - 185 °C.

4. The parasite expelling drug based on milbemycin praziquantel according to claim 1, characterized in that: The compound synergist is composed of febantel and β - cyclodextrin inclusion, and the molar ratio of febantel to β - cyclodextrin is 1:

2.

5. The parasitic expulsion drug based on milbemycin praziquantel according to claim 1, characterized in that: The coating thickness of the nano - coated praziquantel is 10 - 50 nm, and the encapsulation efficiency is ≥90%.

6. The parasite expulsion drug based on milbemycin praziquantel according to claim 5, characterized in that: The particle size of the nano - coated praziquantel is 50 - 200 nm, and the coating material is hydroxypropyl methylcellulose.

7. The parasitic expulsion drug based on milbemycin praziquantel according to claim 1, characterized in that: The flavoring agent is natural chicken powder.

8. The parasitic expulsion drug based on milbemycin praziquantel according to claim 1, characterized in that: The disintegrant is cross - linked carboxymethyl cellulose sodium.

9. Use of the milbemycin praziquantel-based antiparasitic drug according to any one of claims 1-8, characterized in that: The drug is used for preparing a preparation for preventing or treating mixed parasite infections in dogs and cats, and the parasites include tapeworms, nematodes, trematodes, and demodex mites.

10. Use of the milbemycin praziquantel-based antiparasitic drug according to claim 9, characterized in that: The preparation includes tablets, and an ethylcellulose isolation layer with a thickness of 10 - 20 μm is sprayed on the surface of the tablets.

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