A pharmaceutical composition for preventing and treating hydatidosis in animals and a processing method thereof

Abstract

This invention discloses a pharmaceutical composition and processing method for preventing and treating echinococcosis in animals. The raw materials, by weight, include: 0.5-20 parts praziquantel, 2-10 parts sustained-release agent, and 0.01-0.08 parts promoter. The sustained-release agent is prepared by fusing silica aerogel powder and propolis powder in a weight ratio of 1:8-12. This pharmaceutical composition contains only praziquantel as the active ingredient. The sustained-release agent, made from silica aerogel powder and propolis powder in a specific ratio, forms a stable doped sustained-release framework structure, greatly improving the sustained-release synergistic effect. This allows the drug to achieve a high level of prevention and treatment for echinococcosis, while having virtually no toxic side effects, low cost, and can be administered via various methods such as feeding and intramuscular injection.

Description

Technical Field

[0001] This invention relates to the field of veterinary drug technology, specifically to a pharmaceutical composition and processing method for preventing and treating echinococcosis in animals. Background Technology

[0002] Praziquantel is an anthelmintic used in humans and animals, specifically to treat tapeworms and flukes. It is particularly effective against schistosomes, liver flukes, and *Diphyllobothrium latum*. Praziquantel is listed on the World Health Organization's Essential Medicines List and is considered one of the most important medicines for basic public health worldwide. Therefore, praziquantel can be used to prevent and treat echinococcosis in animals.

[0003] Patent document CN107982264A discloses a drug combination for preventing and treating echinococcosis in animals. Its active ingredients include praziquantel, arecoline, cucurbitacin, and osthol, which can effectively treat and cure echinococcosis. However, due to the addition of arecoline, cucurbitacin, and osthol, this drug can only be taken orally and cannot be administered intramuscularly. Furthermore, it is expensive, and arecoline and osthol have significant toxicity and side effects; arecoline is even classified as a Group 2B carcinogen. Therefore, although this composition has a prominent therapeutic effect on echinococcosis, it is not suitable for widespread use by livestock farmers. Summary of the Invention

[0004] The purpose of this invention is to provide a pharmaceutical composition and processing method for preventing and treating echinococcosis in animals. Its active ingredient contains only praziquantel, which also achieves good therapeutic effects on echinococcosis. At the same time, it overcomes the shortcomings of existing drugs of the same kind, such as large toxic side effects, high cost, and only oral administration.

[0005] The present invention achieves the above objectives through the following technical solutions:

[0006] A pharmaceutical composition for preventing and treating echinococcosis in animals, comprising, by weight, 0.5-20 parts of praziquantel, 2-10 parts of a sustained-release agent, and 0.01-0.08 parts of a promoter, wherein the sustained-release agent is prepared by blending silica aerogel powder and propolis powder in a weight ratio of 1:8-12.

[0007] A further improvement is that, by weight, the raw materials used in the preparation also include 5-10 parts of polylactic acid-glycolic acid copolymer.

[0008] A further improvement is that the molecular weight of the polylactic acid-glycolic acid copolymer is 5000-20000 g / mol, and the weight ratio of lactic acid to glycolic acid monomers in the polylactic acid-glycolic acid copolymer is 3-5:1.

[0009] A further improvement is that the accelerator is selected from one or two of Tween, glycerin, and microcrystalline wax.

[0010] The present invention also provides a method for processing the above-mentioned pharmaceutical composition, comprising the steps of:

[0011] Step 1: Mix silica aerogel powder and propolis powder and disperse with 5-10 times the amount of water for injection, then perform ultrasonic fusion treatment on the dispersion.

[0012] Step 2: Take praziquantel and accelerator, add them to the dispersion, stir under vacuum to dissolve, and after the content is qualified, adjust the pH value to 5.5-6.5, then filter with a cellulose filter membrane to remove impurities and obtain the filtrate;

[0013] Step 3: Spray dry the filtrate to obtain the pharmaceutical composition.

[0014] A further improvement is that the ultrasonic fusion processing is performed at a frequency of 20000-50000Hz and a power of 50-200W for 15-40 minutes.

[0015] A further improvement is that the spray drying process refers to spray drying performed using a spray dryer with parameters of 50-65℃ inlet temperature, 300-1000ml / h feed rate, 0.2-0.4MPa atomization pressure, and 20-40Hz power.

[0016] A further improvement is that the pharmaceutical composition is an injection, a spray, or a gastrointestinal dosage form.

[0017] The beneficial effects of this invention are as follows: the drug composition contains only one active ingredient, praziquantel, and a sustained-release agent made of silica aerogel powder and propolis powder in a specific ratio is used to form a stable doped sustained-release framework structure, which greatly improves the sustained-release synergistic effect of the drug, so that the drug can also achieve a high prevention and treatment effect against echinococcosis, while having virtually no toxic side effects, low cost, and can be administered by various methods such as feeding and intramuscular injection. Attached Figure Description

[0018] Figure 1 This is a schematic diagram showing the results of the in vitro release rate test. Detailed Implementation

[0019] The present application will be further described in detail below with reference to the embodiments. It should be noted that the following specific embodiments are only used to further illustrate the present application and should not be construed as limiting the scope of protection of the present application. Those skilled in the art can make some non-essential improvements and adjustments to the present application based on the above application content.

[0020] raw material:

[0021] Praziquantel: Purchased from Shanghai Yuanye Biotechnology Co., Ltd.;

[0022] Polylactic acid-glycolic acid copolymer: purchased from Beijing Bio-Lab Technology Co., Ltd.;

[0023] Glycerin: Purchased from Nantong Runfeng Petrochemical Co., Ltd.;

[0024] Twain: Purchased from Shanghai Yuanye Biotechnology Co., Ltd.;

[0025] Microcrystalline wax: purchased from Nanjing Bermuda Biotechnology Co., Ltd.;

[0026] Silica aerogel powder: purchased from Shanghai Ziming Reagent Factory (Klamar);

[0027] Propolis powder: purchased from Fufeng Sinote Biotechnology Co., Ltd.;

[0028] Gelatin powder: purchased from Shaanxi Runfeng Biotechnology Co., Ltd.;

[0029] Silica powder: purchased from Sichuan Lvcheng Biotechnology Co., Ltd.

[0030] Example 1

[0031] A pharmaceutical composition for preventing and treating echinococcosis in animals, comprising, by weight, the following raw materials: 0.5 parts praziquantel, 5 parts polylactic acid-glycolic acid copolymer, 2 parts sustained-release agent, and 0.01 parts Tween; wherein the sustained-release agent is prepared by fusing silica aerogel powder and propolis powder in a weight ratio of 1:8; the polylactic acid-glycolic acid copolymer has a molecular weight of 5000 g / mol, and the weight ratio of lactic acid to glycolic acid monomers in the polylactic acid-glycolic acid copolymer is 3:1.

[0032] The processing method of the above-mentioned pharmaceutical composition includes the following steps:

[0033] Step 1: Mix silica aerogel powder and propolis powder and disperse with 5 times the amount of water for injection. Then, perform ultrasonic fusion treatment on the dispersion. The ultrasonic fusion treatment conditions are: frequency 20000Hz, power 50W, and ultrasonic treatment for 40 minutes.

[0034] Step 2: Take praziquantel, polylactic acid-glycolic acid copolymer and Tween, add them to the dispersion, stir under vacuum to dissolve, adjust the pH to 5.5 after the content is qualified, and then filter with a cellulose filter membrane to remove impurities and obtain the filtrate;

[0035] Step 3: The filtrate is subjected to spray drying. Spray drying refers to spray drying using a spray dryer with parameters of 50°C inlet temperature, 300ml / h feed rate, 0.2MPa atomization pressure, and 20Hz power to obtain the pharmaceutical composition.

[0036] Example 2

[0037] A pharmaceutical composition for preventing and treating echinococcosis in animals, comprising, by weight, 12 parts praziquantel, 8 parts polylactic acid-glycolic acid copolymer, 6 parts sustained-release agent, and 0.04 parts glycerol, wherein the sustained-release agent is prepared by fusing silica aerogel powder and propolis powder in a weight ratio of 1:10; the polylactic acid-glycolic acid copolymer has a molecular weight of 10000 g / mol, and the weight ratio of lactic acid to glycolic acid monomers in the polylactic acid-glycolic acid copolymer is 4:1.

[0038] The processing method of the above-mentioned pharmaceutical composition includes the following steps:

[0039] Step 1: Mix silica aerogel powder and propolis powder and disperse with 8 times the amount of water for injection. Then, perform ultrasonic fusion treatment on the dispersion. The ultrasonic fusion treatment conditions are 30000Hz frequency and 100W power for 35 minutes.

[0040] Step 2: Take praziquantel, polylactic acid-glycolic acid copolymer and glycerol, add them to the dispersion, stir under vacuum to dissolve, after the content is qualified, adjust the pH value to 6, and then filter with cellulose filter membrane to remove impurities to obtain filtrate;

[0041] Step 3: The filtrate is subjected to spray drying. Spray drying refers to spray drying using a spray dryer with parameters of 55°C inlet temperature, 700ml / h feed rate, 0.3MPa atomization pressure, and 30Hz power to obtain the pharmaceutical composition.

[0042] Example 3

[0043] A pharmaceutical composition for preventing and treating echinococcosis in animals, comprising, by weight, 20 parts praziquantel, 10 parts polylactic acid-glycolic acid copolymer, 10 parts sustained-release agent, and 0.08 parts microcrystalline wax, wherein the sustained-release agent is prepared by fusing silica aerogel powder and propolis powder in a weight ratio of 1:12; the polylactic acid-glycolic acid copolymer has a molecular weight of 20000 g / mol, and the monomer weight ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 5:1.

[0044] The processing method of the above-mentioned pharmaceutical composition includes the following steps:

[0045] Step 1: Mix silica aerogel powder and propolis powder and disperse with 10 times the amount of water for injection. Then, perform ultrasonic fusion treatment on the dispersion. The ultrasonic fusion treatment conditions are: frequency 50000Hz, power 200W, and ultrasonic treatment for 15 minutes.

[0046] Step 2: Take praziquantel, polylactic acid-glycolic acid copolymer and microcrystalline wax, add them to the dispersion, stir under vacuum to dissolve, adjust the pH to 6.5 after the content is qualified, and then filter with cellulose filter membrane to remove impurities to obtain filtrate;

[0047] Step 3: The filtrate is subjected to spray drying. Spray drying refers to spray drying using a spray dryer with parameters of 65°C inlet temperature, 1000ml / h feed rate, 0.4MPa atomization pressure, and 40Hz power to obtain the pharmaceutical composition.

[0048] Example 4

[0049] A pharmaceutical composition for preventing and treating echinococcosis in animals, comprising, by weight, 12 parts praziquantel, 8 parts polylactic acid-glycolic acid copolymer, 6 parts sustained-release agent, and 0.04 parts glycerol, wherein the sustained-release agent is prepared by fusing silica aerogel powder and propolis powder in a weight ratio of 1:5; the polylactic acid-glycolic acid copolymer has a molecular weight of 10000 g / mol, and the weight ratio of lactic acid to glycolic acid monomers in the polylactic acid-glycolic acid copolymer is 4:1.

[0050] The processing method of the above-mentioned pharmaceutical composition includes the following steps:

[0051] Step 1: Mix silica aerogel powder and propolis powder and disperse with 8 times the amount of water for injection. Then, perform ultrasonic fusion treatment on the dispersion. The ultrasonic fusion treatment conditions are 30000Hz frequency and 100W power for 35 minutes.

[0052] Step 2: Take praziquantel, polylactic acid-glycolic acid copolymer and glycerol, add them to the dispersion, stir under vacuum to dissolve, after the content is qualified, adjust the pH value to 6, and then filter with cellulose filter membrane to remove impurities to obtain filtrate;

[0053] Step 3: The filtrate is subjected to spray drying. Spray drying refers to spray drying using a spray dryer with parameters of 55°C inlet temperature, 700ml / h feed rate, 0.3MPa atomization pressure, and 30Hz power to obtain the pharmaceutical composition.

[0054] Example 5

[0055] A pharmaceutical composition for preventing and treating echinococcosis in animals, comprising, by weight, 12 parts praziquantel, 8 parts polylactic acid-glycolic acid copolymer, 6 parts sustained-release agent, and 0.04 parts glycerol, wherein the sustained-release agent is prepared by fusing silica aerogel powder and propolis powder in a weight ratio of 1:15; the polylactic acid-glycolic acid copolymer has a molecular weight of 10000 g / mol, and the weight ratio of lactic acid to glycolic acid monomers in the polylactic acid-glycolic acid copolymer is 4:1.

[0056] The processing method of the above-mentioned pharmaceutical composition includes the following steps:

[0057] Step 1: Mix silica aerogel powder and propolis powder and disperse with 8 times the amount of water for injection. Then, perform ultrasonic fusion treatment on the dispersion. The ultrasonic fusion treatment conditions are 30000Hz frequency and 100W power for 35 minutes.

[0058] Step 2: Take praziquantel, polylactic acid-glycolic acid copolymer and glycerol, add them to the dispersion, stir under vacuum to dissolve, after the content is qualified, adjust the pH value to 6, and then filter with cellulose filter membrane to remove impurities to obtain filtrate;

[0059] Step 3: The filtrate is subjected to spray drying. Spray drying refers to spray drying using a spray dryer with parameters of 55°C inlet temperature, 700ml / h feed rate, 0.3MPa atomization pressure, and 30Hz power to obtain the pharmaceutical composition.

[0060] Comparative Example 1

[0061] A pharmaceutical composition for preventing and treating echinococcosis in animals, comprising, by weight, 12 parts praziquantel, 8 parts polylactic acid-glycolic acid copolymer, 6 parts sustained-release agent, and 0.04 parts glycerol, wherein the sustained-release agent is prepared by fusing silica aerogel powder and gelatin powder in a weight ratio of 1:10; the polylactic acid-glycolic acid copolymer has a molecular weight of 10000 g / mol, and the weight ratio of lactic acid to glycolic acid monomers in the polylactic acid-glycolic acid copolymer is 4:1.

[0062] The processing method of the above-mentioned pharmaceutical composition includes the following steps:

[0063] Step 1: Mix silica aerogel powder and gelatin powder and disperse with 8 times the amount of water for injection. Then, perform ultrasonic fusion treatment on the dispersion. The ultrasonic fusion treatment conditions are: frequency 30000Hz, power 100W, and ultrasonic treatment for 35 minutes.

[0064] Step 2: Take praziquantel, polylactic acid-glycolic acid copolymer and glycerol, add them to the dispersion, stir under vacuum to dissolve, after the content is qualified, adjust the pH value to 6, and then filter with cellulose filter membrane to remove impurities to obtain filtrate;

[0065] Step 3: The filtrate is subjected to spray drying. Spray drying refers to spray drying using a spray dryer with parameters of 55°C inlet temperature, 700ml / h feed rate, 0.3MPa atomization pressure, and 30Hz power to obtain the pharmaceutical composition.

[0066] Comparative Example 2

[0067] A pharmaceutical composition for preventing and treating echinococcosis in animals, comprising, by weight, 12 parts praziquantel, 8 parts polylactic acid-glycolic acid copolymer, 6 parts sustained-release agent, and 0.04 parts glycerol, wherein the sustained-release agent is prepared by fusing silica powder and propolis powder in a weight ratio of 1:10; the polylactic acid-glycolic acid copolymer has a molecular weight of 10000 g / mol, and the weight ratio of lactic acid to glycolic acid monomers in the polylactic acid-glycolic acid copolymer is 4:1.

[0068] The processing method of the above-mentioned pharmaceutical composition includes the following steps:

[0069] Step 1: Mix silica powder and propolis powder and disperse with 8 times the amount of water for injection. Then, subject the dispersion to ultrasonic fusion treatment. The conditions for ultrasonic fusion treatment are: frequency 30000Hz, power 100W, and ultrasonic treatment for 35 minutes.

[0070] Step 2: Take praziquantel, polylactic acid-glycolic acid copolymer and glycerol, add them to the dispersion, stir under vacuum to dissolve, after the content is qualified, adjust the pH value to 6, and then filter with cellulose filter membrane to remove impurities to obtain filtrate;

[0071] Step 3: The filtrate is subjected to spray drying. Spray drying refers to spray drying using a spray dryer with parameters of 55°C inlet temperature, 700ml / h feed rate, 0.3MPa atomization pressure, and 30Hz power to obtain the pharmaceutical composition.

[0072] Performance testing:

[0073] I. In vitro release rate test

[0074] Using the isothermal shaking method, 20 mg of the drug compositions prepared in Examples 1-5 and Comparative Examples 1-2 were weighed and placed in 50 mL volumetric flasks. Phosphate buffer solution with a pH of 7.4 was used as the release medium, and the solution was brought to volume with the release medium to obtain a 200 μg / mL drug composition test solution. 5 mL of the drug composition test solution was placed in a dialysis bag, which was then placed in a flask, and 75 mL of phosphate buffer solution was added. The flask was placed in an isothermal shaking incubator at 37°C and 100 rpm. At 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 24 h, 26 h, 28 h, and 30 h, 5 mL of the release medium was collected, and 75 mL of the release medium was added simultaneously. The content was determined by ultraviolet spectrophotometry, measuring the absorbance, and the dissolution percentage was calculated according to the standard curve equation. A release curve of the drug composition was plotted.

[0075] Reference Figure 1 The figure shows the release curves of the drug compositions. It can be seen that the drug compositions prepared in Examples 1-5 of this invention have good sustained-release effects, significantly better than Comparative Examples 1 and 2, especially Examples 1-3, whose release curves are nearly linear, and the release rate is still only about 60% at 30 hours. In Comparative Example 1, replacing silica aerogel with an equal amount of silica powder significantly accelerated the release rate, achieving complete release at 16 hours. In Comparative Example 2, replacing propolis powder with an equal amount of gelatin powder slightly improved the release rate compared to Comparative Example 1, but still significantly accelerated compared to the other examples, achieving complete release at 24 hours.

[0076] II. Security Testing

[0077] The drug composition prepared in Example 2 was diluted with 5 times the volume of physiological saline to obtain the injectable drug. Sixty healthy sheep aged 6 months were randomly divided into 4 groups of 15 each: a control group, a low-dose group, a medium-dose group, and a high-dose group, and were raised under the same environmental conditions. The control group did not receive the injectable drug but was injected with an equal volume of physiological saline. The low-dose group was administered 5 mg / kg body weight (based on net praziquantel content) per sheep, the medium-dose group was administered 20 mg / kg body weight per sheep, and the high-dose group was administered 50 mg / kg body weight per sheep, via deep intramuscular injection in the neck, once daily for 7 consecutive days.

[0078] After injection, observe the overall condition of each group of sheep, including their spirit, appetite, body temperature, and neurological symptoms. If any sheep die after the experiment, perform an autopsy on the spot within 5 hours of death. If no sheep die, randomly select 2 sheep from each group after the experiment and euthanize them to observe and record the lesions in their organs.

[0079] The results showed that after injection of the drug composition of the present invention, the sheep in each group had normal activity and health status, and no abnormal lesions were found in any organs after necropsy. There were no differences between the groups, which indicates that the drug composition of the present invention has good safety.

[0080] III. Efficacy Testing

[0081] Two sheep farms in Changfeng County and Lujiang County, Hefei City, Anhui Province, were diagnosed with a large-scale infection of cerebral echinococcosis. Symptoms included lethargy, recumbency, listlessness, and pronounced coughing. Forty-eight sheep were randomly selected and divided into six groups of eight each. Drug compositions prepared in Examples 2, 4, 5, Comparative Example 1, and Comparative Example 2 were diluted with five times the volume of physiological saline to obtain injectable drugs. These drugs were administered to sheep in groups 1-5 via a single, multiple-point intramuscular injection at a dose of 20 mg / kg body weight (based on net praziquantel content) into the deep neck muscles, once daily for three days. Group 6 received the same volume of physiological saline. All experimental groups were isolated and carefully cared for. The sheep were observed for 30 days after treatment, during which time they were fed standard sheep feed (without any antibiotics). Their mental state, appetite, body temperature, and neurological symptoms were closely monitored. At the end of the observation period, the mortality rate, effectiveness rate, and cure rate of each group were calculated according to the following criteria.

[0082] Criteria for judging therapeutic efficacy:

[0083] Cure: After treatment, the sheep's spirit, appetite, and body temperature returned to normal, and there were no clinical relapses within 30 days after the medication was administered.

[0084] Effective: After treatment, the sheep's spirits improved, their appetite gradually increased, and their body temperature showed a downward trend.

[0085] Ineffective: After treatment, the sheep's spirit, appetite, and body temperature do not improve significantly, and the sheep may even die.

[0086] The test results are summarized in the table below:

[0087]

[0088] As can be seen from the table above, the pharmaceutical composition prepared using Example 2 of this invention achieved a 100% efficacy rate against echinococcosis, with a cure rate as high as 87.5%, and no deaths, demonstrating significant efficacy. Examples 4 and 5 also showed some therapeutic effect, with a cure rate of 75%, while Comparative Examples 1 and 2 had relatively poor effects, with a cure rate of only 50%, significantly lower than Example 2, and also lower than Examples 4 and 5. This indicates that the sustained-release agent prepared with a specific ratio of silica aerogel powder and propolis powder, when fused together to form a stable doped sustained-release framework structure, greatly enhances the sustained-release synergistic effect of praziquantel.

[0089] The embodiments described above are merely examples of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. A pharmaceutical composition for preventing and treating echinococcosis in animals, characterized in that, The raw materials for preparation, by weight, include: 0.5-20 parts of praziquantel, 5-10 parts of polylactic acid-glycolic acid copolymer, 2-10 parts of sustained-release agent, and 0.01-0.08 parts of accelerator. The sustained-release agent is made by fusing silica aerogel powder and propolis powder in a weight ratio of 1:8-12. The fusion of silica aerogel powder and propolis powder forms a doped sustained-release framework structure, which improves the sustained-release synergistic effect on drug efficacy. The processing steps of the pharmaceutical composition include: Step 1: Mix silica aerogel powder and propolis powder and disperse with 5-10 times the amount of water for injection, then perform ultrasonic fusion treatment on the dispersion. Step 2: Take praziquantel, polylactic acid-glycolic acid copolymer and accelerator, add them to the dispersion, stir and dissolve under vacuum. After the content is qualified, adjust the pH value to 5.5-6.5, then filter with cellulose filter membrane to remove impurities and obtain filtrate. Step 3: Spray dry the filtrate to obtain the pharmaceutical composition.

2. The pharmaceutical composition for preventing and treating echinococcosis in animals according to claim 1, characterized in that, The polylactic acid-glycolic acid copolymer has a molecular weight of 5000-20000 g / mol, and the weight ratio of lactic acid to glycolic acid monomers in the polylactic acid-glycolic acid copolymer is 3-5:

1.

3. The pharmaceutical composition for preventing and treating echinococcosis in animals according to claim 1, characterized in that, The accelerator is selected from one or two of Tween, glycerin, and microcrystalline wax.

4. The pharmaceutical composition for preventing and treating echinococcosis in animals according to claim 1, characterized in that, The conditions for ultrasonic fusion processing are: ultrasonic treatment for 15-40 minutes at a frequency of 20000-50000Hz and a power of 50-200W.

5. The pharmaceutical composition for preventing and treating echinococcosis in animals according to claim 1, characterized in that, The spray drying process refers to spray drying performed using a spray dryer under the following parameters: inlet temperature 50-65℃, feed rate 300-1000ml / h, atomization pressure 0.2-0.4MPa, and power 20-40Hz.

6. The pharmaceutical composition for preventing and treating echinococcosis in animals according to claim 1, characterized in that, The pharmaceutical composition is an injection, a spray, or a gastrointestinal dosage form.

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