CN116726062A - Pharmaceutical composition for treating pet skin diseases and preparation method thereof - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for treating pet skin diseases and a preparation method thereof. It is used to kill insects and acarids in pets, and also has anti-viral, anti-tumor, antibacterial and anti-inflammatory effects. The pharmaceutical composition includes, in parts by weight, The following components: avermectin B2a, fulvic acid, agaricule extract, cleaning and detergent, antifungal and bacterial agent, antibody epiparasite agent and excipients. The preparation method includes preparing Bougainvillea extract, preparing avermectin B2a, mixing raw materials of each component to prepare a mixture, and preparing a pharmaceutical composition. It belongs to the technical field of pet dermatology drugs and preparation methods thereof.

Description

Pharmaceutical composition for treating pet skin diseases and preparation method thereof

Technical field

The invention belongs to the technical field of pet skin disease drugs and preparation methods thereof, and relates to a pharmaceutical composition for treating pet skin diseases and a preparation method thereof.

Background technique

In recent years, rabbit skin disease has become one of the most common clinical diseases. Pet skin diseases are common and can cause itching, hair loss, redness, swelling, and scabs on the pet's skin. They are very harmful and have a high incidence rate. There are many types of pet skin diseases, with parasitic skin diseases and fungal skin diseases being the most common. Parasitic skin diseases in pet dogs mainly include skin diseases caused by Demodex, scabies, and ear itch mites, dermatitis caused by bites of fleas, lice, ticks, etc., as well as hookworm larval dermatitis, and microfilariae of Dirofilaria immitis. Dermatitis, etc. The bacterial skin disease pyoderma in pets is sometimes caused by secondary infection from demodicosis, lacerations, wounds, burns, or dermatitis. Skin diseases caused by fungal infections also account for a considerable proportion, especially during the hot and rainy summer months. The cause of this disease is complex, difficult to diagnose, difficult to treat, and has a high recurrence rate. Over-intensive pet feeding, misuse of antibiotics, unreasonable nutritional intake, and misuse of human shampoo on pets are all factors that contribute to the increased incidence of canine dermatophytosis.

Bougainvillea, also known as Bitter Thorn, Goosefoot Bougainvillea, Sanjiapi, Sanjiapi, is a climbing shrub of the Araliaceae family, mainly growing on forest edges, shrubs or hillsides. Bougainvillea extract has the effects of dispelling wind, dehumidifying, dissipating pain, relieving heat, reducing swelling and detoxifying. The heating reflux method is one of the common extraction methods of Bougainvillea extract. There are few studies on the application of Bougainvillea extract in pet skin disease drugs, and its Traditional preparation methods have drawbacks.

For example, the Chinese patent with publication number CN102961275B discloses a skin cosmetic containing ethanol extract of Bougainvillea. The whole Bougainvillea plant is weighed, 95% ethanol is added 5 times the raw material mass, soaked for 8 to 10 hours, and heated to reflux to extract 2 times, 3h/time, filter, combine the extracts, recover the ethanol from the filtrate under reduced pressure and concentrate it into the ethanol extract of Bougainvillea; in this patented solution, the heated reflux method is used to prepare the Bougainvillea extract, and the extraction time is longer , 3 hours each time, and the extraction rate is low.

Avermectin is a 16-membered macrolide antibiotic produced by fermentation of Streptomyces avermitilis. Its main structure is similar to milbemycin. It is used for agricultural pest control and animal insecticide and acaricidal. It also has antiviral and antibacterial properties. It has tumor, antibacterial, anti-inflammatory and sobering effects. Abamectin B2a is an avermectin derivative. When the traditional supercritical fluid extraction method is used to extract avermectin B2a, the extraction pressure is 35MPa, the _CO2 flow rate is 6.4L/h, and the extraction time is 1.5h. It has the disadvantages of large _CO2 consumption, high operating pressure, and long extraction time, which limits the Its use in pet dermatology medications.

Contents of the invention

The object of the present invention is to provide a pharmaceutical composition for treating pet skin diseases and a preparation method thereof. The anthelmintic ingredient avermectin B2a is added to the medicine, and at the same time, it is combined with the pain-relieving, antipyretic and swelling-reducing effects of the Bougainvillea extract. The pharmaceutical composition of the present invention can be used to kill insects and acarids on pets, and also has anti-viral, anti-tumor, antibacterial and anti-inflammatory effects. It uses fulvic acid as a surfactant system to disperse abamectin B2a and acanthus extract. It is more uniform and can also be used as a synergistic auxiliary for the insecticidal effect of avermectin B2a; the combination of avermectin B2a, fulvic acid, antifungal bacterial agent, and agarwood extract can be effective Prevent and treat common parasitic, bacterial and fungal skin diseases in pets.

The object of the present invention can be achieved through the following technical solutions:

The preparation method of the Bougainvillea extract includes the following steps:

S1. Take the Bougainvillea, wash it, dry it and set aside the Bougainvillea;

S2. Use ethanol as the extraction solution, add the reserved Bougainvillea, control the temperature, and perform ultrasonic treatment. After adding cellulase, perform ultrasonic treatment for a second time, filter the filtrate and concentrate under reduced pressure and vacuum to obtain the Bougainvillea extract.

In the preparation method of Bougainvillea extract, the concentration of ethanol is 40%-70%; the temperature control temperature is 40°C-60°C; the ultrasonic treatment time is 10min; the secondary ultrasonic treatment time is 10-40min; spare Bougainvillea, The mass fraction ratio of ethanol and cellulase is 1:10-30:9-11.

The fulvic acid used in the scheme of the present invention is fulvic acid extracted from the alcohol waste liquid of sugarcane deep processing alcohol;

As a preferred technical solution of the present invention, the cleaning and detergent is decyl glucoside, lauryl glucoside, sodium laureth sulfate, sodium lauryl sulfate, cocamide, cocamide propyl One or more of betaine, cocamide, sodium olefin sulfonate, sodium lauroyl glutamate, ethylene glycol distearate and disodium ethylenediaminetetraacetate.

As a preferred technical solution of the present invention, the antifungal bacterial agent is chlorhexidine acetate, chlorhexidine digluconate, polyaminopropyl biguanide, benzalkonium chloride, benzalkonium bromide, ketoconazole , one or more of fluconazole, itraconazole, clotrimazole, econazole nitrate, miconazole nitrate, nystatin, chloroxylenol and triclosan.

As a preferred technical solution of the present invention, the antibody epiparasite agent is benzyl benzoate, benzoyl peroxide, geranium oil, Melaleuca leucophylla leaf oil, chamomile extract, camphor tree bark oil, one or more of rosemary, leaf oil mixed with lavender oil, peppermint oil, lemongrass leaf oil, rush citronella oil, bay leaf oil and neem seed oil.

As a preferred technical solution of the present invention, the auxiliary materials include anti-allergic and anti-itching agents, moisturizing and hydrating agents, seborrhea control agents, nutrients, conditioning agents, repairing agents, amino acids, protective agents, antiseptic and bacteriostatic agents, acids and bases One or more of the regulators and other plant ingredients.

Wherein, the anti-allergic and anti-itching agent is one or more of colloidal oatmeal powder, aloe vera extract, salicylic acid, hydroxyphenylpropionamide benzoic acid and white willow bark extract;

The nutritional agent is one or both of beeswax or vitamin E;

The conditioning agent is one or more of PEG-12 polydimethylsiloxane, polyquaternium-7 and guar hydroxypropyltrimonium chloride;

The repairing agent is one or more of hyaluronic acid, hexanoyl sphingosine, ceramide EOP, ceramide, cholesterol, bisabolol, linoleic acid, lecithin and hydrogenated lecithin;

The amino acid is one or more of glycine, glutamic acid, leucine, valine, histidine, arginine, taurine, lysine, lysine hydrochloride and cysteine. kind;

The protective agent is one or more of chitin, chitosan, carboxymethyl chitosan, mannose, rhamnose and galactose arabinan;

The antiseptic and bacteriostatic agent is one or more of phenoxyethanol, ethyl hydroxyphenyl ester and p-hydroxyacetophenone;

The acid-base regulator is one or more of citric acid, lactic acid and sodium bicarbonate;

Other botanical ingredients include oat leaf extract, white willow bark extract, aloe vera extract, lavender oil, chamomile flower oil, North American witch hazel extract, geranium oil, citron peel oil, and melaleuca leaf oil. , sunflower oil glycerides, shea butter, chamomile extract, clove bud oil, oregano oil, camphor bark oil, rosemary leaf oil, lavender oil, peppermint oil, lemongrass leaf oil , lemongrass oil, bay leaf oil, North African cedar bark oil, neem seed oil, salvia oil, helichrysum flower oil, jojoba seed oil, sweet almond oil, North American witch hazel extract, cornflower extract one or more of the following: chamomile flower extract, echinacea purpurea root extract and calendula oil;

The scheme of the present invention uses avermectin B2a, and its preparation method includes the following steps:

A1. Abamectin crystallization mother liquor is concentrated under reduced pressure, and after removing the solvent, a solid is obtained;

A2. Accurately weigh the solid matter into the extraction kettle, add triethylene glycol-methyl ether, preheat, pass in CO ₂ , stir, adjust the pressure, extract, and cool to room temperature to obtain a solid-liquid mixture;

A3. Centrifuge the solid-liquid mixture and dry it under reduced pressure to obtain avermectin B2a.

In the preparation method of avermectin B2a, the reduced pressure concentration conditions are that the pressure is -0.1-0.01MPa, and the concentration is until no liquid flows out; the ratio of solid matter: triethylene glycol-methyl ether is 1g:7mL, and the preheating temperature The temperature is 40-50℃, the preheating time is 10min, the _CO2 flow rate is 7L/h, the stirring speed is 45-55r/min, the adjustment pressure is 9MPa, the extraction time is 30min, and centrifuged at 5000r/min for 5min.

A preparation method of a pharmaceutical composition for treating pet skin diseases, the preparation method includes the following steps:

S11. Prepare Bougainvillea extract;

S12. Preparation of abamectin B2a;

S13. Weigh the raw materials according to the corresponding weight portions, add the cleaning detergent and fulvic acid to the blender. After the temperature is controlled, add abamectin B2a and acanthus extract and stir to dissolve, then add antifungal and bacterial agents and antibody expression. After the parasiticide, maintain the temperature and stir evenly to obtain a mixture;

S14. Add excipients to the mixture, cool down, maintain the temperature, and stir thoroughly to obtain a pharmaceutical composition.

As a preferred technical solution of the present invention, in step S13, the temperature is controlled at 60-80°C and the temperature is maintained at 60-80°C.

As a preferred technical solution of the present invention, in step S14, the temperature is maintained at 40-50°C and the stirring time is 10 minutes.

In the aspect of the present invention, the pharmaceutical composition is prepared as shampoo or leave-on foam.

Beneficial effects of the present invention:

(1) The solution of the present invention adds the anthelmintic ingredient avermectin B2a, and at the same time, it is combined with the analgesic, antipyretic and swelling effects of the Bougainvillea extract, so that the pharmaceutical composition of the present invention can be used to kill insects and acarids in pets, and also has anti-inflammatory and anti-inflammatory properties. It has viral, anti-tumor, antibacterial and anti-inflammatory effects. Fulvic acid is used as a surfactant system to disperse avermectin B2a and agaricus extract more evenly. At the same time, it can also be used as a component of the insecticidal effect of avermectin B2a. Synergistic additives; the combination of abamectin B2a, fulvic acid, antifungal agents, bougainvillea extract, and antibacterial agents can effectively prevent and treat common parasitic and bacterial infections on pets’ bodies. and fungal skin diseases.

(2) The use of ultrasound-assisted extraction combined with enzymatic hydrolysis significantly improves the extraction rate of Bougainvillea extract; ultrasound can effectively destroy the cell wall of Bougainvillea and promote the dissolution of more active substances in the Bougainvillea cells into the extraction solvent, thus increasing the amount of Bougainvillea extract. The extraction rate of the vegetable extract; however, the ultrasonic action for a long time destroys the structure of the cellulase and reduces the activity, thereby reducing the extraction rate of the vegetable extract; therefore, the present invention adopts secondary ultrasonic wave The treatment plan is to first pre-treat the prepared Bougainvillea with ultrasonic waves to destroy its cell wall structure, and then use ultrasonic waves combined with enzymatic hydrolysis for simultaneous treatment, which greatly improves the extraction rate of Bougainvillea extract and greatly reduces the extraction process time.

(3) The solution of the present invention combines stirring and supercritical fluid extraction during extraction, which not only saves the amount of CO ₂ , but also reduces the extraction cost, and the entire extraction process is carried out under closed conditions, with a small amount of solvent, which is good for The environment is pollution-free and _CO2 consumption can be saved by 30% to 60%. In addition, the scheme of the present invention uses a small amount of triethylene glycol-methyl ether as an auxiliary extraction solvent to impregnate the sample before supercritical CO ₂ extraction, which enhances the solubility and selectivity of supercritical CO ₂ during the extraction process and reduces the extraction pressure; An extraction method that combines stirring-assisted extraction, triethylene glycol-methyl ether impregnation sample and supercritical _CO2 extraction. Compared with traditional extraction methods, the method of the present invention has the advantages of simple operation, environmental friendliness, high extraction rate, and short extraction time. .

Detailed ways

In order to further elaborate on the technical means and effects adopted by the present invention to achieve the predetermined inventive purpose, the specific implementation manner, structure, characteristics and effects of the present invention are described in detail below in conjunction with the examples.

In the aspect of the present invention, the pharmaceutical composition is a shampoo.

Example 1

A pharmaceutical composition for treating pet skin diseases, the pharmaceutical composition includes the following components in parts by weight:

A preparation method of a pharmaceutical composition for treating pet skin diseases, including the following steps:

S11. Prepare Bougainvillea extract;

S12. Preparation of abamectin B2a;

S13. Weigh the raw materials according to the corresponding weight portions, add decyl glucoside and fulvic acid to the blender, control the temperature at 70°C, add avermectin B2a and Bougainvillea extract, stir and dissolve, then add chlorhexidine acetate After adding benzyl benzoate, keep the temperature at 70°C and stir evenly to obtain a mixture;

S14. Add glutamic acid to the mixture, cool down, maintain the temperature at 45°C, and stir thoroughly for 10 minutes to obtain a pharmaceutical composition.

Example 2

A pharmaceutical composition for treating pet skin diseases, the pharmaceutical composition includes the following components in parts by weight:

A preparation method of a pharmaceutical composition for treating pet skin diseases, including the following steps:

S11. Prepare Bougainvillea extract;

S12. Preparation of abamectin B2a;

S13. Weigh the raw materials according to the corresponding weight portions, add decyl glucoside and fulvic acid to the blender, control the temperature at 70°C, add avermectin B2a and Bougainvillea extract, stir and dissolve, then add chlorhexidine acetate After adding benzyl benzoate, keep the temperature at 70°C and stir evenly to obtain a mixture;

S14. Add glutamic acid to the mixture, cool down, maintain the temperature at 45°C, and stir thoroughly for 10 minutes to obtain a pharmaceutical composition.

Example 3

A pharmaceutical composition for treating pet skin diseases, the pharmaceutical composition includes the following components in parts by weight:

A preparation method of a pharmaceutical composition for treating pet skin diseases, including the following steps:

S11. Prepare Bougainvillea extract;

S12. Preparation of abamectin B2a;

S13. Weigh the raw materials according to the corresponding weight portions, add decyl glucoside and fulvic acid to the blender, control the temperature at 70°C, add avermectin B2a and Bougainvillea extract, stir and dissolve, then add chlorhexidine acetate After adding benzyl benzoate, keep the temperature at 70°C and stir evenly to obtain a mixture;

S14. Add glutamic acid to the mixture, cool down, maintain the temperature at 45°C, and stir thoroughly for 10 minutes to obtain a pharmaceutical composition.

Example 4

The preparation method of the Bougainvillea extract includes the following steps:

S1. Take the Bougainvillea, wash it, dry it and set aside the Bougainvillea;

S2. Use ethanol with a concentration of 40% as the extraction solution, add spare Bougainvillea, control the temperature at 40°C, and conduct ultrasonic treatment for 10 minutes. After adding cellulase, perform ultrasonic treatment for 10 minutes for a second time. After filtration, take the filtrate and concentrate it under reduced pressure to obtain Bougainvillea extraction. material; among them, the mass fraction ratio of standby bougainvillea, ethanol and cellulase is 1:10:9.

Example 5

The preparation method of the Bougainvillea extract includes the following steps:

S1. Take the Bougainvillea, wash it, dry it and set aside the Bougainvillea;

S2. Use ethanol with a concentration of 55% as the extraction solution, add spare Bougainvillea, control the temperature at 50°C, and conduct ultrasonic treatment for 10 minutes. After adding cellulase, perform ultrasonic treatment for 30 minutes for a second time. After filtration, take the filtrate and concentrate it under reduced pressure to obtain Bougainvillea extraction. material; among them, the mass fraction ratio of standby bougainvillea, ethanol and cellulase is 1:25:10.

Example 6

The preparation method of the Bougainvillea extract includes the following steps:

S1. Take the Bougainvillea, wash it, dry it and set aside the Bougainvillea;

S2. Use ethanol with a concentration of 70% as the extraction solution, add spare Bougainvillea, control the temperature at 60°C, and conduct ultrasonic treatment for 10 minutes. After adding cellulase, perform ultrasonic treatment for 40 minutes for a second time. After filtration, take the filtrate and concentrate it under reduced pressure to obtain Bougainvillea extraction. material; among them, the mass fraction ratio of standby bougainvillea, ethanol and cellulase is 1:30:11.

Comparative example 1

Compared with Example 5, the difference is that ethanol with a concentration of 30% is used as the extraction solution, and the remaining preparation steps and parameters are the same.

Comparative example 2

Compared with Example 5, the difference is that ethanol with a concentration of 80% is used as the extraction solution, and the remaining preparation steps and parameters are the same.

Comparative example 3

Compared with Example 5, the difference is that in step S2, ethanol with a concentration of 55% is used as the extraction solution, and standby Bougainvillea is added, and the temperature is controlled at 50°C. After cellulase is added, ultrasonic treatment is performed for 30 minutes, and filtered. The filtrate was concentrated under reduced pressure and vacuum to obtain the Bougainvillea extract. The remaining preparation steps and parameters were the same.

Comparative example 4

Compared with Example 5, the difference is that in step S2, ethanol with a concentration of 55% is used as the extraction solution, and standby bougainvillea is added, and the temperature is controlled at 50°C. After cellulase is added, ultrasonic treatment is performed for 40 minutes, and filtered. The filtrate was concentrated under reduced pressure and vacuum to obtain the Bougainvillea extract. The remaining preparation steps and parameters were the same.

Comparative example 5

Compared with Example 5, the difference is that in step S2, ethanol with a concentration of 55% is used as the extraction solution, and the prepared bougainvillea is added, the temperature is controlled at 50°C, and ultrasonic treatment is performed for 10 minutes. After adding cellulase, enzymatic hydrolysis treatment 40 min. After filtration, take the filtrate and concentrate it under reduced pressure to obtain the Bougainvillea extract. The remaining preparation steps and parameters are the same.

Comparative example 6

Compared with Example 5, the difference is that in step S2, ethanol with a concentration of 55% is used as the extraction solution, and standby Bougainvillea is added, and the temperature is controlled at 50°C. After cellulase is added, enzymatic hydrolysis is performed for 40 minutes, and after filtration The filtrate was concentrated under reduced pressure to obtain the Bougainvillea extract. The remaining preparation steps and parameters were the same.

Comparative example 7

Compared with Example 5, the difference is that in step S2, ethanol with a concentration of 55% is used as the extraction solution, and the standby bougainvillea is added, the temperature is controlled at 50°C, and ultrasonic treatment is performed for 40 minutes. After filtration, the filtrate is taken and concentrated under reduced pressure and vacuum to obtain Bougainvillea extract, the remaining preparation steps and parameters are the same.

Comparative example 8

Compared with Example 5, the difference is that in step S2, ethanol with a concentration of 55% is used as the extraction solution, and the standby bougainvillea is added, the temperature is controlled at 50°C, and ultrasonic treatment is performed for 50 minutes. After filtration, the filtrate is taken and concentrated under reduced pressure and vacuum to obtain Bougainvillea extract, the remaining preparation steps and parameters are the same.

The total flavonoids in the Bougainvillea extract have the effects of dispelling wind and dampness, dispersing pain and antipyretic, reducing swelling and detoxification; respectively measure 5ml of the Bougainvillea extract of Examples 4-6 and Comparative Examples 1-8 and place it in a 25ml volumetric flask and add distilled water Shake evenly to the mark, measure the absorbance at a wavelength of 500 nm, and calculate the total flavonoid content in the Bougainvillea extract according to the regression equation. The test results are shown in Table 1.

Table 1

Total flavonoid content Example 4 4.54% Example 5 4.81% Example 6 4.61% Comparative example 1 3.78% Comparative example 2 3.59% Comparative example 3 3.85% Comparative example 4 3.81% Comparative example 5 3.91% Comparative example 6 3.88% Comparative example 7 3.79% Comparative example 8 3.79%

It can be seen from the test results in Table 1 that in Examples 4-6 compared with Comparative Examples 1-2, when the concentration of ethanol is too low, it is not conducive to the dissolution of flavonoids. When the volume fraction of ethanol is increased, the driving force of the solvent also increases. The increase is beneficial to the dissolution of flavonoids. If the concentration of ethanol is too high, it will reduce the extraction effect of total flavonoids from Bougainvillea. Too high concentration of ethanol extract will inhibit the activity of cellulase; Example 4-6 and Compared with Comparative Examples 3-8, ultrasonic treatment before enzymatic hydrolysis can effectively destroy the cell wall of Bougainvillea, which facilitates the enzymatic hydrolysis reaction and shortens the enzymatic hydrolysis time. Then, enzymatic hydrolysis and ultrasonic treatment are carried out at the same time, synergistically promoting each other. More active substances in the cells of Bougainvillea are dissolved into the extraction solvent, but the ultrasonic action for a long time destroys the structure of the cellulase and reduces its activity, thus reducing the extraction rate of the Bougainvillea extract; therefore , the scheme of the present invention adopts a secondary ultrasonic treatment scheme, first pre-treating the prepared Bougainvillea with ultrasonic waves to destroy its cell wall structure, and then using a process of ultrasonic combined with enzymatic hydrolysis for simultaneous treatment, which greatly improves the extraction rate of Bougainvillea extract and greatly reduces the extraction process. time.

Example 7

The preparation method of avermectin B2a includes the following steps:

A1. Abamectin crystallization mother liquor is concentrated under reduced pressure at a pressure of 0.01MPa until no liquid flows out. After removing the solvent, a solid is obtained;

A2. Accurately weigh the solid matter into the extraction kettle, add triethylene glycol-methyl ether, preheat at 45°C for 10 minutes, introduce CO ₂ at a flow rate of 7L/h, stir at a speed of 50r/min, and adjust The pressure is 9MPa, extract for 30 minutes, and after cooling to room temperature, a solid-liquid mixture is obtained; where the ratio of solid: triethylene glycol-methyl ether is 1g:7mL;

A3. Centrifuge the solid-liquid mixture at 5000r/min for 5 minutes, and then dry it under reduced pressure to obtain avermectin B2a.

Comparative example 9

Compared with Example 7, the difference is that in step A2, triethylene glycol-methyl ether is added, CO ₂ is introduced at a flow rate of 7 L/h at 45°C, and stirred at a rotation speed of 50 r/min. Adjust the pressure to 9MPa and extract for 30 minutes. After cooling to room temperature, a solid-liquid mixture is obtained. The remaining preparation steps and parameters are the same.

Comparative example 10

Compared with Example 7, the difference is that in step A2, triethylene glycol-methyl ether is added, preheated at 45°C for 10 minutes, CO ₂ is introduced at a flow rate of 7L/h, the pressure is adjusted to 9MPa, and extraction is performed After cooling to room temperature for 30 min, a solid-liquid mixture was obtained. The remaining preparation steps and parameters were the same.

Comparative example 11

Compared with Example 7, the difference is that in step A2, triethylene glycol-methyl ether is added, preheated at 45°C for 10 minutes, CO ₂ is introduced at a flow rate of 7L/h, the pressure is adjusted to 9MPa, and extraction is performed After cooling to room temperature for 1 hour, a solid-liquid mixture was obtained. The remaining preparation steps and parameters were the same.

The avermectin B2a prepared in Example 7 and Comparative Examples 9-11 were tested for the avermectin B2a extraction rate respectively, and the test results are shown in Table 2.

Table 2

Extraction rate of avermectin B2a Example 7 98.7% Comparative example 9 95.7% Comparative example 10 81.7% Comparative example 11 94.3%

It can be seen from the test results in Table 2 that compared with Comparative Examples 9-11 in Example 7, the scheme of the present invention uses a small amount of triethylene glycol-methyl ether as an auxiliary extraction solvent to impregnate the sample before supercritical CO ₂ extraction, which enhances the extraction The solubility and selectivity of supercritical CO ₂ during the process reduce the extraction pressure; the extraction method that combines stirring-assisted extraction, triethylene glycol-methyl ether impregnation sample and supercritical CO ₂ extraction greatly shortens the extraction time compared with traditional extraction methods. Extraction time, reducing the waste of _CO2 resources, has the advantages of high extraction rate and short extraction time.

Comparative Example 12-14

Compared with Example 2, the difference is that the weight parts of avermectin B2a, fulvic acid and Bougainvillea extract in Comparative Examples 12-14 are as shown in Table 3, and the remaining preparation steps and parameters are the same. .

table 3

1. The shampoo prepared from the pharmaceutical composition in Examples 1-3 and Comparative Examples 12-14 was subjected to a clinical efficacy test on bacterial skin disease in New Zealand rabbits.

1. Experimental animals

A total of 60 naturally occurring cases of bacterial skin disease in New Zealand rabbits were selected.

2. Experimental methods

(1) Clinical examination: Conduct clinical systemic and local examinations, as well as necessary skin scraping examinations.

(2) Microbiological examination: Collect samples from the affected parts of the case animals, isolate and identify the pathogenic bacteria, and finally count the pathogenic bacteria.

(3) Administration method

Dampen your rabbit's coat with water and apply shampoo all over your body, avoiding your eyes, nose, and mouth. Shampoo and massage, keeping product in contact with skin and fur for 10 minutes. Rinse clean with water, and wear an Elizabethan collar to ensure the rabbit does not lick itself or foam during the bath. The test drug was used twice a week, and the shampoo dosage was 1-2 mg/kg of animal each time.

(4) Efficacy evaluation indicators

Cure: After treatment, the isolation and conversion rate of pathogenic bacteria on the skin is ≥80%. At the same time, inflammatory secretions disappear significantly, the affected area has no odor, rash, dander, pus, etc., and itching symptoms disappear significantly.

Effective: After treatment, the isolation and conversion rate of pathogenic bacteria on the skin is ≥60%. At the same time, inflammatory secretions are reduced, the affected area is basically odorless, rashes, dandruff, pus, etc. are reduced, and itching symptoms are alleviated.

Ineffective: After treatment, the isolation rate of pathogenic bacteria on the skin is less than 60%. At the same time, the inflammatory secretions still exist, the affected area still has a peculiar smell, the rash, dander, pus, etc. have not been reduced, and the affected area still has obvious swelling. Itching symptoms.

3. Test results

Efficacy evaluation results

Table 4 Results of clinical efficacy test on bacterial skin disease in New Zealand rabbits

It can be seen from Table 4 that the pet shampoo of the pharmaceutical composition of the present invention has a cure rate of more than 90% for rabbits suffering from bacterial skin diseases.

2. The shampoo prepared from the pharmaceutical composition in Examples 1-3 and Comparative Examples 12-14 was subjected to a clinical efficacy test on fungal skin diseases in New Zealand rabbits.

1. Experimental animals

A total of 60 naturally occurring cases of fungal skin diseases in New Zealand rabbits were selected.

2. Experimental methods

(1) Clinical examination: Conduct clinical systemic and local examinations, as well as necessary skin scraping examinations

(2) Microbiological examination: Collect samples from the affected parts of the case animals, isolate and identify the pathogenic bacteria, and finally count the pathogenic bacteria.

(3) Administration method

Dampen your rabbit's coat with water and apply shampoo all over your body, avoiding your eyes, nose, and mouth. Shampoo and massage, keeping product in contact with skin and fur for 10 minutes. Rinse clean with water, and wear an Elizabethan collar to ensure the rabbit does not lick itself or foam during the bath. The test drug was used twice a week, and the shampoo dosage was 1-2 mg/kg of animal each time.

(4) Efficacy evaluation indicators

Cure: After treatment, the isolation and negative conversion rate of pathogenic fungi on the skin is ≥80%. At the same time, inflammatory secretions disappear significantly, the affected area has no odor, rash, dander, pus, etc., and itching symptoms disappear significantly.

Effective: After treatment, the isolation and conversion rate of pathogenic fungi on the skin is ≥60%. At the same time, inflammatory secretions are reduced, the affected area is basically odorless, rashes, dander, pus, etc. are reduced, and itching symptoms are alleviated.

Ineffective: After treatment, the isolation rate of pathogenic fungi on the skin is less than 60%. At the same time, the inflammatory secretions still exist, the affected area still has a peculiar smell, the rash, dander, pus, etc. have not been reduced, and the affected area still has obvious swelling. Itching symptoms.

3. Test results

Efficacy evaluation results

Table 5 Results of clinical efficacy test on fungal skin diseases in New Zealand rabbits

It can be seen from Table 5 that the pet shampoo of the pharmaceutical composition of the present invention has a cure rate of more than 80% for rabbits suffering from fungal skin diseases.

3. The shampoo prepared from the pharmaceutical composition in Examples 1-3 and Comparative Examples 12-14 was subjected to a clinical efficacy test on parasitic skin diseases in New Zealand rabbits.

1. Experimental animals

A total of 60 naturally occurring cases of parasitic skin diseases in New Zealand rabbits were selected.

2. Experimental methods

(1) Clinical examination: Conduct clinical systemic examination, including body temperature, respiration, heart rate and other conventional indicators; local examination of the degree of itching on the body surface, degree of skin damage, the number of rashes or pustules, and the location and distribution of skin lesions.

(2) Examination of ectoparasites: Take the skin of the affected area, observe it under a microscope and count the number of ectoparasites in the local lesions. For flea infections: count and count the number of fleas, distribution and quantity of flea droppings; for tick bite dermatitis: count and count the number of ticks and skin lesions.

(3) Administration method

Dampen your rabbit's coat with water and apply shampoo all over your body, avoiding your eyes, nose, and mouth. Shampoo and massage, keeping product in contact with skin and fur for 10 minutes. Rinse clean with water, and wear an Elizabethan collar to ensure the rabbit does not lick itself or foam during the bath. The test drug was administered with shampoo twice a week, and the dosage of shampoo per application was 1-2 mg/kg of animal.

(4) Efficacy evaluation indicators:

Effective: During and after treatment, the average reduction rate of the number of external parasites on the skin is ≥90%, and there is no itching, rash, dander or self-gnawing damage on the affected area.

Ineffective: During and after the medication, the average reduction rate of the number of external parasites on the skin is <90%, the affected area still has itching, rash, dander, etc., and self-gnawing injuries of the animal are obvious.

3. Experimental results

(1) Efficacy evaluation results

Table 6 Results of clinical efficacy test for treating parasitic skin diseases in New Zealand rabbits

It can be seen from Table 6 that the pet shampoo of the pharmaceutical composition of the present invention has a cure rate of more than 90% for rabbits suffering from parasitic skin diseases.

Based on the test results in Table 4-6, it can be seen that the solution of the present invention adds the anthelmintic ingredient avermectin B2a together with the extract of Bougainvillea and fulvic acid, so that the pharmaceutical composition of the present invention can be used to kill insects and acarids on pets, and also has antiviral properties. , antibacterial and anti-inflammatory effects, the combination of abamectin B2a, fulvic acid, antifungal agents, agaricus extract, and antibacterial agents can effectively prevent and treat common pet surface parasites, Bacterial and fungal skin diseases.

The above are only preferred embodiments of the present invention, and do not limit the present invention in any form. Although the present invention has been disclosed above in preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art , without departing from the scope of the technical solution of the present invention, the technical contents disclosed above can be used to make some changes or modifications to equivalent embodiments with equivalent changes. However, without departing from the technical solution of the present invention, according to the technical solution of the present invention, In essence, any brief modifications, equivalent changes and modifications made to the above embodiments still fall within the scope of the technical solution of the present invention.

Claims (10)

1. The pharmaceutical composition for treating the skin diseases of the pets is characterized by comprising the following components in parts by weight:

the preparation method of the trifoliate acanthopanax extract comprises the following steps:

s1, cleaning and airing trifoliate acanthopanax to obtain spare trifoliate acanthopanax;

s2, taking ethanol as an extracting solution, adding the spare trifoliate acanthopanax, controlling the temperature, performing ultrasonic treatment, adding cellulase, performing ultrasonic secondary treatment, filtering, taking filtrate, and concentrating under reduced pressure and vacuum to obtain the trifoliate acanthopanax extract.

2. A pharmaceutical composition for treating skin disorders in pets according to claim 1, wherein: the concentration of the ethanol is 40% -70%; the temperature is controlled to be 40-60 ℃; the ultrasonic treatment time is 10min; the ultrasonic secondary treatment time is 10-40min; the mass ratio of the spare trifoliate acanthopanax, ethanol and cellulase is 1:10-30:9-11.

3. A pharmaceutical composition for treating skin disorders in pets according to claim 1, wherein: the cleaning detergent is one or more of decyl glucoside, lauryl glucoside, sodium laureth sulfate, cocamide, cocamidopropyl betaine, cocamide, sodium olefin sulfonate, sodium lauroyl glutamate, ethylene glycol distearate and disodium edetate.

4. A pharmaceutical composition for treating skin disorders in pets according to claim 1, wherein: the antifungal bacterial agent is one or more of chlorhexidine acetate, chlorhexidine digluconate, polyurethane biguanide, benzalkonium chloride, benzalkonium bromide, ketoconazole, fluconazole, itraconazole, clotrimazole, econazole nitrate, miconazole nitrate, nystatin, chloroxylenol and triclosan.

5. A pharmaceutical composition for treating skin disorders in pets according to claim 1, wherein: the antibody surface parasite agent is one or more of benzyl benzoate, benzoyl peroxide, geranium oil, green flower cajeput leaf oil, chamomile extract, camphor tree bark oil, rosemary, leaf oil hybrid lavender oil, peppermint oil, lemon citronella leaf oil, chinese iris oil, bay leaf oil and neem seed oil.

6. A pharmaceutical composition for treating skin disorders in pets according to claim 1, wherein: the auxiliary materials comprise one or more of anti-sensitive antipruritic agent, moistening and moisturizing agent, sebum overflow control agent, nutritional agent, conditioner, repairing agent, amino acid, protective agent, antiseptic antibacterial agent, acid-base regulator and other plant component agents.

7. The pharmaceutical composition for treating skin diseases of pets according to claim 1, wherein the preparation method of the abamectin B2a comprises the following steps:

a1, concentrating the avermectin crystallization mother liquor under reduced pressure, and removing the solvent to obtain a solid;

a2, accurately weighing solid matters in an extraction kettle, adding triethylene glycol-methyl ether, preheating, and introducing CO ₂ Stirring, regulating pressure, extracting, cooling to room temperature to obtain a solid-liquid mixture;

and A3, centrifuging the solid-liquid mixture, and drying under reduced pressure to obtain the avermectin B2a.

8. A pharmaceutical composition for treating skin disorders in pets according to claim 7, wherein: concentrating under reduced pressure of-0.1-0.01 MPa until no liquid flows out; solid matter: the triethylene glycol-methyl ether ratio is 1g:7mL, preheating temperature of 40-50deg.C, preheating time of 10min, CO ₂ The flow is 7L/h, the stirring rotation speed is 45-55r/min, the pressure is regulated to 9MPa, the extraction time is 30min, and the separation is carried out at the rotation speed of 5000r/minHeart for 5min.

9. A method of preparing a pharmaceutical composition for the treatment of skin disorders in pets according to any of claims 1 to 8, characterized in that said method of preparation comprises the following steps:

s11, preparing an trifoliate acanthopanax extract;

s12, preparing avermectin B2a;

s13, weighing raw materials according to corresponding parts by weight, adding a cleaning detergent and fulvic acid into a stirrer, controlling the temperature, adding abamectin B2a and an acanthopanax trifoliatus extract, stirring and dissolving, adding an antifungal bacterial agent and an antibody surface parasite agent, maintaining the temperature, and stirring uniformly to obtain a mixture;

s14, adding auxiliary materials into the mixture, cooling, keeping the temperature, and fully stirring to obtain the pharmaceutical composition.

10. The method for preparing a pharmaceutical composition for treating skin diseases of pets according to claim 9, wherein in step S13, the temperature is controlled to be 60-80 ℃ and maintained at 60-80 ℃; in step S14, the temperature is maintained at 40-50deg.C and the stirring time is 10min.