A pharmaceutical composition for treating pet skin diseases and preparation method thereof

Abstract

The present invention relates to a pharmaceutical composition for treating pet skin diseases and a preparation method thereof, which is used for killing insects and mites for pets and also has antiviral, antitumor, antibacterial and anti-inflammatory effects. The pharmaceutical composition comprises the following components by weight: avermectin B2a, fulvic acid, rambutan extract, cleaning detergent, antifungal bacterial agent, antiparasitic agent and auxiliary materials. The preparation method comprises preparing rambutan extract, preparing avermectin B2a, mixing raw materials of various components to prepare a mixture and preparing the pharmaceutical composition. The invention belongs to the technical field of pet skin disease drugs and preparation methods thereof.

Description

Technical Field

[0001] The invention belongs to the technical field of pet skin disease medicines and preparation methods thereof, and relates to a medicine composition for treating pet skin diseases and a preparation method thereof. Background Art

[0002] In recent years, rabbit skin disease is one of the most common clinical diseases. Pet skin disease is a common disease that can cause itching, hair loss, redness, swelling, scabs, etc. on pet skin, which is very harmful and has 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 mites, scabies mites, and ear mites, dermatitis caused by bites of fleas, lice, ticks, hookworm larvae dermatitis, microfilariae dermatitis of canine heartworms, etc. Sometimes secondary infection caused by demodex mites, lacerations, trauma, burns or dermatitis causes pet bacterial skin disease pyoderma. Skin diseases caused by fungal infections also account for a considerable proportion, especially in the hot and rainy summer season. The cause of this disease is complex, difficult to diagnose, difficult to treat, and has a high recurrence rate. Over-crowding of pets, misuse of antibiotics, unreasonable nutritional intake, and the misuse of human shampoo on pets are all factors that contribute to the increased incidence of canine skin fungal diseases.

[0003] Basang, also known as bitter thorn, goosefoot sedge, three-leafed aralia, and three-leafed aralia, is a climbing shrub of the Araliaceae family, mainly growing on forest edges, bushes or hillsides. Basang extract has the effects of dispelling wind and dampness, relieving pain and relieving fever, and reducing swelling and detoxification. Heating reflux method is one of the common extraction methods of Basang extract; there are few studies on the application of Basang extract in pet skin disease drugs, and its traditional preparation method has defects.

[0004] For example, a Chinese patent with publication number CN102961275B discloses a skin cosmetic containing ethanol extract of leucophylla, which comprises weighing the whole herb of leucophylla, adding 95% ethanol of 5 times the mass of the raw material, soaking for 8 to 10 hours, heating and refluxing extraction for 2 times, 3 hours each time, filtering, combining the extracts, and recovering ethanol from the filtrate under reduced pressure to concentrate it into ethanol extract of leucophylla; in this patent scheme, the leucophylla extract is prepared by utilizing the heating and reflux method, and the extraction time is relatively long, 3 hours each time, and the extraction rate is low.

[0005] 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 insecticide and acaricide of animals. It also has antiviral, anti-tumor, antibacterial, anti-inflammatory and hangover effects. Avermectin B2a is an avermectin derivative. When extracting Avermectin B2a by traditional supercritical fluid extraction method, the extraction pressure is 35MPa, the CO2 flow rate is 6.4L / h, and the extraction time is 1.5h. There are defects such as large CO2 dosage, high operating pressure and long extraction time, which limit its use in pet skin disease drugs. Summary of the invention

[0006] 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, the medicine is combined with the analgesic, antipyretic and detumescent effects of leucanthemum extract, so that the pharmaceutical composition of the present invention can be used for killing insects and mites for pets, and also has antiviral, antitumor, antibacterial and anti-inflammatory effects. Fulvic acid is used as a surfactant system to make avermectin B2a and leucanthemum extract disperse more evenly, and at the same time, it can also serve as a synergistic auxiliary agent for the insecticidal effect of avermectin B2a; the combination of avermectin B2a, fulvic acid, antifungal bacterial agent and leucanthemum extract can effectively prevent and treat common pet surface parasitic, bacterial and fungal skin diseases.

[0007] The purpose of the present invention can be achieved through the following technical solutions:

[0008]

[0009] The preparation method of the oleander extract comprises the following steps:

[0010] S1. Take the basil, wash it, and dry it for later use;

[0011] S2. Use ethanol as the extracting liquid, add the reserved basil, control the temperature, perform ultrasonic treatment, add cellulase, perform ultrasonic treatment for the second time, filter and take the filtrate, and concentrate under reduced pressure and vacuum to obtain the basil extract.

[0012] In the preparation method of araucaria extract, the concentration of ethanol is 40%-70%; the temperature control temperature is 40℃-60℃; the ultrasonic treatment time is 10min; the ultrasonic secondary treatment time is 10-40min; the mass fraction ratio of araucaria, ethanol and cellulase is 1:10-30:9-11.

[0013] 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;

[0014] As a preferred technical solution of the present invention, the cleaning detergent is one or more of decyl glucoside, lauryl glucoside, sodium laureth sulfate, sodium lauryl sulfate, cocamide, cocamidopropyl betaine, cocamide, sodium olefin sulfonate, sodium lauroyl glutamate, ethylene glycol distearate and disodium ethylenediaminetetraacetic acid.

[0015] As a preferred technical solution of the present invention, the antifungal bacterial agent is one or more of chlorhexidine acetate, chlorhexidine digluconate, polyaminopropyl biguanide, benzalkonium chloride, benzalkonium bromide, ketoconazole, fluconazole, itraconazole, clotrimazole, econazole nitrate, miconazole nitrate, nystatin, chloroxylenol and triclosan.

[0016] As a preferred technical solution of the present invention, the antiparasitic agent is one or more of benzyl benzoate, benzoyl peroxide, geranium oil, nelumbo nucifera leaf oil, white chamomile extract, camphor bark oil, rosemary, leaf oil mixed with lavender oil, peppermint oil, lemongrass leaf oil, citronella oil, bay leaf oil and neem seed oil.

[0017] As a preferred technical solution of the present invention, the auxiliary materials include one or more of anti-allergic and antipruritic agents, moisturizing and hydrating agents, sebum secretion control agents, nutrients, conditioners, repair agents, amino acids, protective agents, preservatives and antibacterial agents, acid-base regulators and other plant ingredients.

[0018] Wherein, the anti-allergic and antipruritic agent is one or more of colloidal oatmeal powder, aloe extract, salicylic acid, hydroxyphenylpropionamide benzoic acid and white willow bark extract;

[0019] The nutrient agent is one or both of beeswax and vitamin E;

[0020] The conditioning agent is one or more of PEG-12 polydimethylsiloxane, polyquaternium-7 and guar hydroxypropyltrimonium chloride;

[0021] The repair agent is one or more of hyaluronic acid, hexanoyl sphingosine, ceramide EOP, ceramide, cholesterol, bisabolol, linoleic acid, lecithin and hydrogenated lecithin;

[0022] The amino acid is one or more of glycine, glutamic acid, leucine, valine, histidine, arginine, taurine, lysine, lysine hydrochloride and cysteine;

[0023] The protective agent is one or more of chitosan, deacetylated chitosan, carboxymethyl deacetylated chitosan, mannose, rhamnose and galactoarabinan;

[0024] The antiseptic and antibacterial agent is one or more of phenoxyethanol, ethylparaben and p-hydroxyacetophenone;

[0025] The acid-base regulator is one or more of citric acid, lactic acid and sodium bicarbonate;

[0026] The other plant ingredients are one or more of oat leaf extract, white willow bark extract, aloe extract, lavender oil, chamomile flower oil, witch hazel extract, geranium oil, citron peel oil, niaouli leaf oil, sunflower seed oil glyceride, shea butter, white chamomile extract, clove bud oil, oregano oil, camphor bark oil, rosemary leaf oil, lavender oil, peppermint oil, lemongrass leaf oil, citronella oil, laurel leaf oil, North African cedar bark oil, neem seed oil, salvia oil, Italian helichrysum flower oil, jojoba seed oil, sweet almond oil, witch hazel extract, cornflower extract, chamomile flower extract, purple coneflower root extract and calendula oil;

[0027] The scheme of the present invention adopts avermectin B2a, and its preparation method comprises the following steps:

[0028] A1, avermectin crystallization mother liquor is concentrated under reduced pressure, and after removing the solvent, a solid is obtained;

[0029] A2. Accurately weigh the solid matter in an extraction kettle, add triethylene glycol-methyl ether, preheat, introduce CO2, stir, adjust the pressure, extract, and cool to room temperature to obtain a solid-liquid mixture;

[0030] A3. After centrifuging the solid-liquid mixture, it is dried under reduced pressure to obtain avermectin B2a.

[0031] In the preparation method of avermectin B2a, the reduced pressure concentration conditions are a pressure of -0.1-0.01MPa, and concentration until no liquid flows out; the ratio of solid matter: triethylene glycol-methyl ether is 1g:7mL, the preheating temperature is 40-50°C, the preheating time is 10min, the CO2 flow rate is 7L / h, the stirring speed is 45-55r / min, the pressure is adjusted to 9MPa, the extraction time is 30min, and centrifugation is carried out at a speed of 5000r / min for 5min.

[0032] A method for preparing a pharmaceutical composition for treating pet skin diseases, the preparation method comprising the following steps:

[0033] S11, preparing a balsam pear extract;

[0034] S12, preparing avermectin B2a;

[0035] S13, weighing the raw materials according to the corresponding weight parts, adding the cleaning detergent and fulvic acid into the blender, controlling the temperature, adding avermectin B2a and baicalensis extract, stirring and dissolving, adding the antifungal bacterial agent and the antiparasitic agent, maintaining the temperature, stirring evenly, and obtaining a mixture;

[0036] S14, adding auxiliary materials to the mixture, cooling and lowering the temperature, maintaining the temperature, and stirring thoroughly to obtain a pharmaceutical composition.

[0037] As a preferred technical solution of the present invention, in step S13, the temperature is controlled at 60-80°C and maintained at 60-80°C.

[0038] 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.

[0039] In the scheme of the present invention, the pharmaceutical composition is prepared as shampoo or disposable foam.

[0040] Beneficial effects of the present invention:

[0041] (1) The present invention adds the anthelmintic ingredient avermectin B2a, and at the same time, cooperates with the analgesic, antipyretic and detumescent effects of the ramie extract, so that the pharmaceutical composition of the present invention can be used for killing insects and mites for pets, and also has antiviral, antitumor, antibacterial and anti-inflammatory effects. By using fulvic acid as a surfactant system, avermectin B2a and ramie extract are dispersed more evenly, and can also serve as a synergistic auxiliary agent for the insecticidal effect of avermectin B2a; the combination of avermectin B2a, fulvic acid, antifungal agent, ramie extract and antibacterial agent can effectively prevent and treat common pet surface parasitic, bacterial and fungal skin diseases.

[0042] (2) The extraction rate of the leek extract was significantly improved by using ultrasound-assisted extraction combined with enzymatic hydrolysis. Ultrasonic waves can effectively destroy the cell walls of the leek, promote the dissolution of more effective substances in the leek cells into the extraction solvent, and thus increase the extraction rate of the leek extract. However, prolonged ultrasonic action destroys the structure of the cellulase and reduces its activity, thereby reducing the extraction rate of the leek extract. Therefore, the present invention adopts a secondary ultrasonic treatment scheme, firstly pre-treating the leek with ultrasound to destroy its cell wall structure, and then using ultrasound combined with enzymatic hydrolysis to simultaneously treat the leek, thereby greatly improving the extraction rate of the leek extract and greatly reducing the extraction process time.

[0043] (3) The present invention combines stirring and supercritical fluid extraction during extraction, which not only saves CO2 usage, but also reduces extraction costs. The entire extraction process is carried out under closed conditions, with less solvent usage, and no pollution to the environment. The CO2 usage can be saved by 30% to 60%. In addition, before supercritical CO2 extraction, the present invention uses a small amount of triethylene glycol-methyl ether as an auxiliary extraction solvent to impregnate the sample, which enhances the solubility and selectivity of supercritical CO2 during the extraction process and reduces the extraction pressure. Compared with traditional extraction methods, the present invention has the advantages of simple operation, environmental friendliness, high extraction rate, and short extraction time. DETAILED DESCRIPTION

[0044] In order to further illustrate the technical means and effects adopted by the present invention to achieve the predetermined invention purpose, the specific implementation methods, structures, features and effects of the present invention are described in detail below in combination with embodiments.

[0045] In the scheme of the present invention, the pharmaceutical composition is prepared as shampoo.

[0046] Example 1

[0047] A pharmaceutical composition for treating pet skin diseases, comprising the following components by weight:

[0048]

[0049] A method for preparing a pharmaceutical composition for treating pet skin diseases comprises the following steps:

[0050] S11, preparing a balsam pear extract;

[0051] S12, preparing avermectin B2a;

[0052] S13, weighing the raw materials according to corresponding weight parts, adding decyl glucoside and fulvic acid into a blender, controlling the temperature at 70° C., adding avermectin B2a and arachis japonica extract, stirring and dissolving, adding chlorhexidine acetate and benzyl benzoate, maintaining the temperature at 70° C., stirring evenly, to obtain a mixture;

[0053] S14, adding glutamic acid to the mixture, cooling and maintaining the temperature at 45° C., and stirring thoroughly for 10 minutes to obtain a pharmaceutical composition.

[0054] Example 2

[0055] A pharmaceutical composition for treating pet skin diseases, comprising the following components by weight:

[0056]

[0057]

[0058] A method for preparing a pharmaceutical composition for treating pet skin diseases comprises the following steps:

[0059] S11, preparing a balsam pear extract;

[0060] S12, preparing avermectin B2a;

[0061] S13, weighing the raw materials according to corresponding weight parts, adding decyl glucoside and fulvic acid into a blender, controlling the temperature at 70° C., adding avermectin B2a and arachis japonica extract, stirring and dissolving, adding chlorhexidine acetate and benzyl benzoate, maintaining the temperature at 70° C., stirring evenly, to obtain a mixture;

[0062] S14, adding glutamic acid to the mixture, cooling and maintaining the temperature at 45° C., and stirring thoroughly for 10 minutes to obtain a pharmaceutical composition.

[0063] Example 3

[0064] A pharmaceutical composition for treating pet skin diseases, comprising the following components by weight:

[0065]

[0066] A method for preparing a pharmaceutical composition for treating pet skin diseases comprises the following steps:

[0067] S11, preparing a balsam pear extract;

[0068] S12, preparing avermectin B2a;

[0069] S13, weighing the raw materials according to corresponding weight parts, adding decyl glucoside and fulvic acid into a blender, controlling the temperature at 70° C., adding avermectin B2a and arachis japonica extract, stirring and dissolving, adding chlorhexidine acetate and benzyl benzoate, maintaining the temperature at 70° C., stirring evenly, to obtain a mixture;

[0070] S14, adding glutamic acid to the mixture, cooling and maintaining the temperature at 45° C., and stirring thoroughly for 10 minutes to obtain a pharmaceutical composition.

[0071] Example 4

[0072] The preparation method of the oleander extract comprises the following steps:

[0073] S1. Take the basil, wash it, and dry it for later use;

[0074] S2. Use 40% ethanol as the extracting solution, add the reserved basil, control the temperature at 40°C, treat with ultrasound for 10 minutes, add cellulase, treat with ultrasound for a second time for 10 minutes, filter, take the filtrate and concentrate under reduced pressure to obtain the basil extract; wherein the mass fraction ratio of the reserved basil, ethanol and cellulase is 1:10:9.

[0075] Example 5

[0076] The preparation method of the oleander extract comprises the following steps:

[0077] S1. Take the basil, wash it, and dry it for later use;

[0078] S2. Use 55% ethanol as the extracting solution, add the reserved basil, control the temperature at 50°C, perform ultrasonic treatment for 10 minutes, add cellulase, perform ultrasonic treatment for a second time for 30 minutes, filter, take the filtrate, and concentrate it under reduced pressure to obtain the basil extract; wherein the mass fraction ratio of the reserved basil, ethanol and cellulase is 1:25:10.

[0079] Example 6

[0080] The preparation method of the oleander extract comprises the following steps:

[0081] S1. Take the basil, wash it, and dry it for later use;

[0082] S2. Use 70% ethanol as the extracting solution, add the reserved basil, control the temperature at 60°C, perform ultrasonic treatment for 10 minutes, add cellulase, perform ultrasonic treatment for a second time for 40 minutes, filter, take the filtrate, decompress and vacuum concentrate to obtain the basil extract; wherein the mass fraction ratio of the reserved basil, ethanol and cellulase is 1:30:11.

[0083] Comparative Example 1

[0084] Compared with Example 5, the difference is that 30% ethanol is used as the extracting liquid, and the other preparation steps and parameters are the same.

[0085] Comparative Example 2

[0086] Compared with Example 5, the difference is that 80% ethanol is used as the extracting liquid, and the other preparation steps and parameters are the same.

[0087] Comparative Example 3

[0088] Compared with Example 5, the difference is that in step S2, 55% ethanol is used as the extracting solution, the reserved taro is added, the temperature is controlled at 50°C, cellulase is added, ultrasonic treatment is performed for 30 minutes, the filtrate is filtered, and the filtrate is concentrated under reduced pressure to obtain the taro extract, and the other preparation steps and parameters are the same.

[0089] Comparative Example 4

[0090] Compared with Example 5, the difference is that in step S2, 55% ethanol is used as the extracting solution, the reserved taro is added, the temperature is controlled at 50°C, cellulase is added, ultrasonic treatment is performed for 40 minutes, the filtrate is filtered, and the filtrate is concentrated under reduced pressure to obtain the taro extract, and the other preparation steps and parameters are the same.

[0091] Comparative Example 5

[0092] Compared with Example 5, the difference is that in step S2, 55% ethanol is used as the extracting solution, the reserved taro is added, the temperature is controlled at 50°C, ultrasonic treatment is performed for 10 minutes, cellulase is added, enzymatic hydrolysis is performed for 40 minutes, the filtrate is filtered, and the filtrate is concentrated under reduced pressure to obtain a taro extract, and the other preparation steps and parameters are the same.

[0093] Comparative Example 6

[0094] Compared with Example 5, the difference is that in step S2, 55% ethanol is used as the extracting solution, the reserved taro is added, the temperature is controlled at 50°C, cellulase is added, the enzymatic hydrolysis is carried out for 40 minutes, the filtrate is filtered, and the filtrate is concentrated under reduced pressure to obtain the taro extract, and the other preparation steps and parameters are the same.

[0095] Comparative Example 7

[0096] Compared with Example 5, the difference is that in step S2, 55% ethanol is used as the extracting solution, the reserved taro is added, the temperature is controlled at 50°C, ultrasonic treatment is performed for 40 minutes, and the filtrate is filtered and concentrated under reduced pressure to obtain the taro extract, and the other preparation steps and parameters are the same.

[0097] Comparative Example 8

[0098] Compared with Example 5, the difference is that in step S2, 55% ethanol is used as the extracting solution, the reserved taro is added, the temperature is controlled at 50°C, ultrasonic treatment is performed for 50 minutes, and the filtrate is filtered and vacuum concentrated to obtain the taro extract, and the other preparation steps and parameters are the same.

[0099] The total flavonoids in the taro extract have the effects of dispelling wind and dampness, relieving pain and relieving fever, reducing swelling and detoxifying; 5 ml of the taro extract of Examples 4-6 and Comparative Examples 1-8 were respectively measured and placed in a 25 ml volumetric flask, distilled water was added to the scale and shaken well, the absorbance was measured at a wavelength of 500 nm, and the content of total flavonoids in the taro extract was calculated according to the regression equation. The test results are shown in Table 1.

[0100] Table 1

[0101] Total flavonoids 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％

[0102] From the test results in Table 1, it can be seen that when the concentration of ethanol in Examples 4-6 is too low compared with Comparative Examples 1-2, it is not conducive to the dissolution of flavonoid components. When the volume fraction of ethanol is increased, the driving force of the solvent also increases, which is conducive to the dissolution of flavonoid components. If the concentration of ethanol is too high, the extraction effect of total flavonoids from leucanthemum is reduced. An ethanol extract with too high a concentration will inhibit the activity of cellulase. Compared with Comparative Examples 3-8, in Examples 4-6, ultrasonic treatment before enzymatic hydrolysis can effectively destroy the cell wall of leucanthemum, which is conducive to the enzymatic hydrolysis reaction and shortens the enzymatic hydrolysis time. In the process of ultrasonic treatment, the enzymatic treatment and ultrasonic treatment are carried out simultaneously, which cooperate with each other to promote the dissolution of more effective substances in the cells of the leek into the extraction solvent. However, the ultrasonic action for too long destroys the structure of the cellulase and reduces its activity, thereby reducing the extraction rate of the leek extract. Therefore, the scheme of the present invention adopts a secondary ultrasonic treatment scheme, firstly, the leek is pretreated with ultrasound to destroy its cell wall structure, and then ultrasound combined with enzymatic treatment are used to treat the leek at the same time, which greatly improves the extraction rate of the leek extract and greatly reduces the extraction process time.

[0103] Example 7

[0104] The preparation method of avermectin B2a comprises the following steps:

[0105] A1, avermectin crystallization mother liquor is concentrated under reduced pressure at a pressure of 0.01 MPa until no liquid flows out, and after removing the solvent, a solid is obtained;

[0106] A2. Accurately weigh the solid matter in an extraction kettle, add triethylene glycol-methyl ether, preheat at 45°C for 10 min, introduce CO2 at a flow rate of 7 L / h, stir at a speed of 50 r / min, adjust the pressure to 9 MPa, extract for 30 min, and cool to room temperature to obtain a solid-liquid mixture; wherein the ratio of solid matter: triethylene glycol-methyl ether is 1 g:7 mL;

[0107] A3. The solid-liquid mixture was centrifuged at a speed of 5000 r / min for 5 min, and then dried under reduced pressure to obtain avermectin B2a.

[0108] Comparative Example 9

[0109] Compared with Example 7, the difference is that in step A2, triethylene glycol monomethyl ether is added, CO2 is introduced at a flow rate of 7 L / h at 45°C, the mixture is stirred at a speed of 50 r / min, the pressure is adjusted to 9 MPa, extraction is performed for 30 min, and the mixture is cooled to room temperature to obtain a solid-liquid mixture, and the remaining preparation steps and parameters are the same.

[0110] Comparative Example 10

[0111] Compared with Example 7, the difference is that in step A2, triethylene glycol monomethyl ether is added, preheated at 45°C for 10 min, CO2 is introduced at a rate of 7 L / h, the pressure is adjusted to 9 MPa, extraction is carried out for 30 min, and after cooling to room temperature, a solid-liquid mixture is obtained, and the remaining preparation steps and parameters are the same.

[0112] Comparative Example 11

[0113] Compared with Example 7, the difference is that in step A2, triethylene glycol monomethyl ether is added, preheated at 45°C for 10 min, CO2 is introduced at a rate of 7 L / h, the pressure is adjusted to 9 MPa, extraction is carried out for 1 h, and after cooling to room temperature, a solid-liquid mixture is obtained, and the remaining preparation steps and parameters are the same.

[0114] The avermectin B2a prepared in Example 7 and Comparative Examples 9-11 were tested for the extraction rate of avermectin B2a. The test results are shown in Table 2.

[0115] Table 2

[0116] Extraction rate of avermectin B2a Example 7 98.7％ Comparative Example 9 95.7％ Comparative Example 10 81.7％ Comparative Example 11 94.3％

[0117] 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 CO2 extraction, which enhances the solubility and selectivity of supercritical CO2 during the extraction process and reduces the extraction pressure; the extraction method combining stirring-assisted extraction, triethylene glycol-methyl ether impregnation of the sample and supercritical CO2 extraction greatly shortens the extraction time and reduces the waste of CO2 resources compared to the traditional extraction method, and has the advantages of high extraction rate and short extraction time.

[0118] Comparative Examples 12-14

[0119] Compared with Example 2, the difference is that the weight proportions of avermectin B2a, fulvic acid and balsam pear extract in Comparative Examples 12-14 are as shown in Table 3, and the other preparation steps and parameters are the same.

[0120] Table 3

[0121]

[0122]

[0123] 1. The shampoos prepared from the pharmaceutical compositions of Examples 1-3 and Comparative Examples 12-14 were tested for their therapeutic effects on clinical bacterial skin diseases in New Zealand rabbits.

[0124] 1. Experimental Animals

[0125] A total of 60 naturally occurring cases of bacterial skin diseases in New Zealand rabbits were selected.

[0126] 2. Experimental methods

[0127] (1) Clinical examination: Perform systemic and local examinations, as well as skin scraping examinations if necessary.

[0128] (2) Microbiological examination: Samples are collected from the affected parts of the case animals to isolate and identify the pathogens, and finally the pathogens are counted.

[0129] (3) Method of administration

[0130] Soak the rabbit's hair with water and apply the shampoo all over the body, avoiding the eyes, nose and mouth. Wash and massage, making sure the product is in contact with the skin and fur for 10 minutes. Rinse with water and put on an Elizabethan collar to ensure that the rabbit does not lick itself or foam during bathing. The test drug is used twice a week, and the amount of shampoo used each time is 1-2mg / kg animal.

[0131] (4) Efficacy evaluation indicators

[0132] Cure: After taking the medicine, the isolation rate of pathogenic bacteria on the skin turns negative ≥ 80%. At the same time, the inflammatory secretions disappear significantly, there is no odor in the affected area, the rash, dandruff, pustules, etc. disappear significantly, and the itching symptoms disappear significantly.

[0133] Effective: After taking the medicine, the isolation and conversion rate of pathogenic bacteria on the skin is ≥60%. At the same time, inflammatory secretions are reduced, there is basically no odor in the affected area, rashes, dandruff, pustules, etc. are reduced, and itching symptoms are alleviated.

[0134] Ineffective: After taking the medicine, the isolation rate of pathogenic bacteria on the skin turned negative in less than 60%. At the same time, inflammatory secretions still existed, the affected area still had an odor, the rash, dandruff, pustules, etc. did not decrease, and the affected area still had obvious itching symptoms.

[0135] 3. Test results

[0136] Efficacy evaluation results

[0137] Table 4 Results of clinical bacterial skin disease treatment trial in New Zealand rabbits

[0138]

[0139] It can be seen from Table 4 that the cure rate of the pet shampoo of the pharmaceutical composition of the present invention on rabbits suffering from bacterial skin diseases is over 90%.

[0140] 2. The shampoo prepared from the pharmaceutical compositions of Examples 1-3 and Comparative Examples 12-14 was tested for the therapeutic effect on New Zealand rabbits with clinical fungal skin diseases.

[0141] 1. Experimental Animals

[0142] A total of 60 naturally occurring cases of fungal skin diseases in New Zealand rabbits were selected.

[0143] 2. Experimental methods

[0144] (1) Clinical examination: Perform systemic and local examinations, as well as skin scraping examinations if necessary

[0145] (2) Microbiological examination: Samples are collected from the affected parts of the case animals to isolate and identify the pathogens, and finally the pathogens are counted.

[0146] (3) Method of administration

[0147] Soak the rabbit's hair with water and apply the shampoo all over the body, avoiding the eyes, nose and mouth. Wash and massage, making sure the product is in contact with the skin and fur for 10 minutes. Rinse with water and put on an Elizabethan collar to ensure that the rabbit does not lick itself or foam during bathing. The test drug is used twice a week, and the amount of shampoo used each time is 1-2mg / kg animal.

[0148] (4) Efficacy evaluation indicators

[0149] Cure: After taking the medicine, the isolation rate of pathogenic fungi on the skin turns negative ≥ 80%. At the same time, the inflammatory secretions disappear significantly, there is no odor in the affected area, the rash, dandruff, pustules, etc. disappear significantly, and the itching symptoms disappear significantly.

[0150] Effective: After taking the medicine, the isolation and conversion rate of pathogenic fungi on the skin is ≥60%. At the same time, inflammatory secretions are reduced, there is basically no odor in the affected area, rashes, dandruff, pustules, etc. are reduced, and itching symptoms are alleviated.

[0151] Ineffective: After taking the medicine, the isolation rate of pathogenic fungi on the skin turned negative in less than 60%. At the same time, inflammatory secretions still existed, the affected area still had an odor, the rash, dandruff, pustules, etc. did not decrease, and the affected area still had obvious itching symptoms.

[0152] 3. Test results

[0153] Efficacy evaluation results

[0154] Table 5 Results of clinical fungal skin disease treatment test in New Zealand rabbits

[0155]

[0156] 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.

[0157] 3. The shampoo prepared from the pharmaceutical compositions of Examples 1-3 and Comparative Examples 12-14 was tested for the therapeutic effect on clinical parasitic skin diseases in New Zealand rabbits.

[0158] 1. Experimental Animals

[0159] A total of 60 natural cases of parasitic skin diseases in New Zealand rabbits were selected.

[0160] 2. Experimental methods

[0161] (1) Clinical examination: A full-body clinical examination is performed, including routine indicators such as body temperature, respiration, and heart rate; local examination is performed to check the degree of itching on the body surface, the degree of skin damage, the number of rashes or pustules, and the location and distribution of skin lesions.

[0162] (2) Examination of external parasites: Take the skin of the affected area and observe and count the number of external parasites in the local lesions under a microscope. For flea infestation: count and count the number of fleas, the distribution and number of flea feces; for tick bite dermatitis: count and count the number of ticks and the condition of skin lesions.

[0163] (3) Method of administration

[0164] Soak the rabbit's hair with water and apply shampoo all over the body, avoiding the eyes, nose and mouth. Wash and massage, making sure the product is in contact with the skin and fur for 10 minutes. Rinse with water and put on an Elizabethan collar to ensure that the rabbit does not lick itself or foam during bathing. The test drug is used twice a week, and the amount of shampoo used each time is 1-2mg / kg animal.

[0165] (4) Efficacy evaluation indicators:

[0166] Effective: During and after the treatment, the average reduction rate of the number of external parasites on the skin was ≥90%, and there was no itching, rash, dandruff or self-biting injuries on the affected area.

[0167] Ineffective: During and after the treatment, the average reduction rate of the number of external parasites on the skin was <90%, and the affected area still had itching, rashes, dandruff, etc., and animal self-gnaw injuries were obvious.

[0168] 3. Experimental results

[0169] (1) Efficacy evaluation results

[0170] Table 6 Results of clinical parasitic skin disease treatment test in New Zealand rabbits

[0171]

[0172] As can be seen from Table 6, the cure rate of the pet shampoo of the pharmaceutical composition of the present invention for rabbits suffering from parasitic skin diseases is over 90%.

[0173] From the test results in Tables 4-6, it can be seen that the solution of the present invention adds the anthelmintic ingredient avermectin B2a in combination with taro extract and fulvic acid, so that the pharmaceutical composition of the present invention can be used for killing insects and mites for pets, and also has antiviral, antibacterial and anti-inflammatory effects. The combination of avermectin B2a, fulvic acid, antifungal agents, taro extracts, and antibacterial agents can effectively prevent and treat common pet surface parasitic, bacterial and fungal skin diseases.

[0174] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technical personnel in this field can make some changes or modify the technical contents disclosed above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any brief modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A pharmaceutical composition for treating pet skin diseases, characterized in that: The pharmaceutical composition is made of the following ingredients by weight: Avermectin B2a 0.3-0.8 parts Fulvic acid 1-2 parts 2-5 parts of balsam pear extract 10-15 parts cleaning detergent 1-2 parts of antifungal bacteria Antiparasitic agent 0.5-0.8 parts Auxiliary materials 0.5-1 part Wherein, the cleaning detergent is decyl glucoside; The antifungal bacterial agent is chlorhexidine acetate; The antiparasitic agent is benzyl benzoate; The auxiliary material is glutamic acid; Wherein, the preparation method of the taro extract comprises the following steps: S1. Take the basil, wash it, and dry it for later use; S2. Using ethanol as the extracting liquid, adding the reserved arachis, controlling the temperature, ultrasonic treatment, adding cellulase, ultrasonic secondary treatment, filtering the filtrate, decompressing and vacuum concentrating to obtain the arachis extract; the ethanol concentration is 40%-70%; the temperature is controlled at 40℃-60℃; the ultrasonic treatment time is 10min; the ultrasonic secondary treatment time is 10-40min; the ratio of the reserved arachis, ethanol and cellulase by mass fraction is 1:10-30:9-11; The preparation method of avermectin B2a comprises the following steps: A1, avermectin crystallization mother liquor is concentrated under reduced pressure, and after removing the solvent, a solid is obtained; A2. Accurately weigh the solid matter in an extraction kettle, add triethylene glycol-methyl ether, preheat, introduce CO2, stir, adjust the pressure, extract, and cool to room temperature to obtain a solid-liquid mixture; A3. After centrifuging the solid-liquid mixture, it is dried under reduced pressure to obtain avermectin B2a.

2. A pharmaceutical composition for treating pet skin diseases according to claim 1, characterized in that: The conditions for reduced pressure concentration are: pressure of -0.1-0.01MPa, concentration until no liquid flows out; solid matter: triethylene glycol-methyl ether ratio is 1g:7mL, preheating temperature is 40-50℃, preheating time is 10min, CO2 flow rate is 7L / h, stirring speed is 45-55r / min, pressure is adjusted to 9MPa, extraction time is 30min, and centrifugation is carried out at 5000r / min for 5min.

3. A method for preparing a pharmaceutical composition for treating pet skin diseases according to any one of claims 1 to 2, characterized in that: The preparation method comprises the following steps: S11, preparing a balsam pear extract; S12, preparing avermectin B2a; S13, weighing the raw materials according to the corresponding weight parts, adding the cleaning detergent and fulvic acid into the blender, controlling the temperature, adding avermectin B2a and baicalensis extract, stirring and dissolving, adding the antifungal bacterial agent and the antiparasitic agent, maintaining the temperature, stirring evenly, and obtaining a mixture; S14, adding auxiliary materials to the mixture, cooling and lowering the temperature, maintaining the temperature, and stirring thoroughly to obtain a pharmaceutical composition.

4. The method for preparing the pharmaceutical composition for treating pet skin diseases according to claim 3, characterized in that: In step S13, the temperature is controlled at 60-80°C and maintained at 60-80°C; in step S14, the temperature is maintained at 40-50°C and the stirring time is 10 minutes.

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