JP7271014B2 - Shampoo for pets with functions of treating skin diseases caused by ectoparasites and antibacterial, and manufacturing method - Google Patents

Description

FIELD OF THE INVENTION The present invention relates to the field of pet daily cosmetic cleansers, and in particular to pet shampoos with functions of treating skin diseases caused by ectoparasites and antibacterial and methods of preparation.

In recent years, skin disease in dogs and cats is one of the most common clinical diseases. Pet skin diseases occur frequently, causing itching, hair loss, redness, swelling, crusting, etc. on the skin of pets, which is harmful and has a high incidence. There are many types of pet skin diseases, with parasitic and fungal skin diseases being the most common. Parasitic skin diseases in pet dogs include skin diseases caused mainly by demodex, scabies and house dust mites; dermatitis caused by flea, louse and tick bites; dermatitis caused by heartworm larvae; Filaria dermatitis, etc. Secondary infection by Demodex mites, lacerations, wounds, burns, or dermatitis can cause pyoderma, a bacterial skin disease in pets. Skin diseases caused by fungal infections also account for a significant proportion, especially during the hot and wet summer months. The cause of this disease is complex, difficult to diagnose, difficult to treat, and has a high recurrence rate. Over-intensive breeding of pets, abuse of antibiotics, malnutrition, and abuse of human shampoos on pets are all factors contributing to the increased incidence of canine fungal disease.

Most pet skin diseases can be determined by observation with the naked eye, and for topical pet skin problems, shampoo therapy reduces allergens and microbes, reduces irritation, eliminates infection, and thereby normalizes the skin. It restores the healthy skin surface microenvironment, leaving your pet's fur soft, shiny and easy to comb. The Chinese invention patent with publication number CN108553335A provides a medicated shampoo with the function of preventing and treating pet skin diseases and its preparation method for fungal infections, bacterial infections and mixed fungal and bacterial pet skin diseases. It has a good therapeutic effect on skin diseases, but it does not have a good therapeutic effect on parasitic skin diseases.

Fipronil is a novel phenylpyrazole insecticide, a suitable drug for repelling ectoparasites in pets such as dogs, cats, etc. With the characteristics of broad spectrum and high efficiency, it is widely used in multiple agricultural fields. While it is an important insecticide, fipronil is sparingly soluble in water and easily soluble in organic solvents such as acetone. cannot be used. Therefore, how to effectively dissolve fipronil in a shampoo system to prepare a pet shampoo with stable system, favorable viscosity, insecticidal, antifungal, and antibacterial properties is a common pet shampoo. There is a high need for prevention and treatment of superficial parasitic, bacterial and fungal skin diseases.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a pet shampoo having the function of treating skin diseases caused by ectoparasites and antibacterial, and a method for producing it. Shampoo contains the insecticidal component fipronil, and the complex system of specific surfactants solves the problem that fipronil is difficult to dissolve. Also with certain amino acid thickeners, by thickening the anionic shampoo system, it can play a good thickening effect, the shampoo system can reach the desired viscosity, the product is stable, fipronil, antimycotic, By combining the three components of the antibacterial agent, it is possible to effectively prevent and treat common pet parasitic, bacterial and fungal skin diseases.

The main object of the present invention is to provide a pet shampoo with the function of treating ectoparasitic skin diseases and antibacterial.

Another object of the present invention is to provide a method for producing the pet shampoo.

The above objects of the present invention are achieved by the following technical solutions.
The present invention provides a pet shampoo with the function of treating skin diseases caused by ectoparasites and antibacterial, the pet shampoo has a total weight of 100 parts, 0.1-2 parts of fipronil, 1-5 parts of Antifungal, 1-5 parts antibacterial, 5-15 parts alkyl glucoside (APG), 20-30 parts cocamidopropyl betaine (CAB), 2-10 parts dodecyldimethylamine oxide (OB-2 ), 1-10 parts thickener, 0.1-2 parts chelating agent, 0.1-5 parts conditioner, 0.01-1 part preservative, balance deionized water.

In the pet shampoo according to the present invention, fipronil can effectively repel fleas and ticks on the body surface of pets and treat parasite infections as an insect repellent, while fipronil is poorly soluble in water. , It is easily soluble in organic solvents such as acetone, and according to the "Cosmetic Safety Technical Specifications", organic solvents such as acetone cannot be used in cosmetics and pet shampoos. The specific surfactant conjugate system of the present invention, namely, the three surfactant conjugates of alkyl glycoside (APG), cocamidopropyl betaine (CAB) and dodecyldimethylamine oxide (OB-2), are both Can be used in shampoo systems. Although fipronil, an insect repellent for pets, is sparingly soluble in water, it is soluble in organic solvents such as acetone that are harmful to pet skin, and these organic solvents cannot be added to pet shampoo systems. By providing a non-toxic and innovative surfactant complex formula that can be applied to shampoo, by dissolving fipronil, it not only solves the problem that fipronil is difficult to dissolve, but also solves the problem of shampoo foaming and foam stabilization. .

Antimicrobial ingredients in shampoos have excellent anti-bacterial and anti-fungal action and prevent secondary infections by parasites. The present invention effectively treats common parasitic skin diseases, bacterial skin diseases, and fungal skin diseases of pets by combining three components, an insect repellent, an antifungal agent, and an antibacterial agent. can be prevented and treated.

Preferably, said pet shampoo comprises 0.2-2 parts fipronil, 1-3 parts antifungal agent, 1-3 parts antibacterial agent, 6-15 parts alkyl glucoside, with a total weight of 100 parts. , 20-30 parts cocamidopropyl betaine, 6-10 parts dodecyldimethylamine oxide, 1-5 parts thickener, 0.1-1 part chelating agent, 0.1-1 part conditioner, Contains 0.01 to 0.125 parts preservative, balance deionized water.

Preferably, the weight ratio of said alkyl glycoside, cocamidopropyl betaine and dodecyldimethylamine oxide is 10-15:20-30:10. The complex ratio allows rapid and complete dissolution in the fipronil repellent.

Preferably, said thickener is cetearyl glucoside, acrylic acid ester copolymer emulsion (SF-1), thickener-SCC68, fatty alcohol polyglycol ether (VD-92), PEG-120 methylglucose dioleate one or more of (DOE-120).

More preferably, said thickener is one or more of DOE-120, VD-92 or thickener-SCC68.

Shampoo systems are generally anionic, but the antibacterial agents and conditioners added to the formulation are cationic surfactants, which causes the problem of difficulty in thickening the shampoo system. When using general high molecular weight polymer thickeners, it is easy to discolor at high temperatures, easy to become jelly at low temperatures, suppress the abundance of surfactant foam, and when washing, the skin feels like high molecular weight. Influenced by raw materials, specifically, problems such as stickiness, uncleanliness, strong residual feeling, and decreased light viscosity appear. Therefore, in order to overcome the above problems, the present invention thickens shampoo by selecting a specific amino acid thickener, can achieve good thickening effect, the solution is transparent, Shampoo systems can be made more stable.

Preferably, said antifungal agent is one or more of ketoconazole, econazole nitrate, miconazole nitrate, clotrimazole, fluconazole.

Preferably, the antibacterial agent is one or more of benzalkonium chloride, benzalkonium bromide, chlorhexidine diacetate hydrate, chlorhexidine gluconate, triclosan, polyhexamethylene biguanide.

Preferably, the chelating agent is one or more of ethylenediamine, ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetate.

Preferably, said conditioner is one or more of cetrimonium chloride (1631), water-soluble lanolin, aminosilicone oil, aminosilicone oil microemulsion.

Preferably, said preservative is one or more of potassium sorbate, sodium dehydroacetate, sodium benzoate, isothiazolinone.

The present invention further provides a method for producing the above pet shampoo, the method comprising:
First, deionized water, which accounts for 35% of the total volume of the shampoo, is heated to 60-80°C, then the alkyl glucoside, cocamidopropyl betaine and dodecyldimethylamine oxide are added to the deionized water and stirred to dissolve, After complete dissolution, fipronil is added. After fipronil is completely dissolved, the antifungal agent is added and dissolved by stirring while heating to maintain 60 to 80 ° C. until the antifungal agent is sufficiently dissolved. (1) adding a conditioner and stopping heating after the conditioner has completely dissolved;
After stopping heating in step (1), the chelating agent is added and stirred to dissolve, and when cooled to 40-50 ° C., the antibacterial agent is added and stirred to dissolve, and the antibacterial agent is completely dissolved. After dissolving, the thickener is added and stirred to dissolve, and after the thickener is completely dissolved, the preservative and the remaining deionized water are added and uniformly stirred to obtain step (2). include.

Preferably, in step (1) deionized water is heated to 70-80°C.

According to the study of the present invention, it was found that the manufacturing process has a clear influence on the dissolution effect of fipronil, such as alkyl glucoside, cocamidopropyl betaine, dodecyldimethylamine oxide and conditioner raw materials in step (1). The order of addition is not arbitrary, first add alkyl glucoside, cocamidopropyl betaine, and dodecyl dimethylamine oxide to deionized water and stir to dissolve, then add fipronil, antifungal agent and conditioner in order, It accelerates the dissolution of fipronil and increases its viscosity. In addition, the heating temperature also has an obvious effect on the dissolution of fipronil. Fipronil does not dissolve at all when the heating temperature is below 30 ° C. , shampoo viscosity is high.

The shampoo having the function of treating skin diseases caused by ectoparasites of pets and the antibacterial function according to the present invention has a simple manufacturing process and high operability.

Compared with the prior art, the present invention has the following beneficial effects.
(1) By adding a safe and non-toxic specific surfactant formulation of alkylglucoside, cocamidopropyl betaine and dodecyldimethylamine oxide to the pet shampoo of the present invention, it only solves the problem that fipronil is difficult to dissolve. It enhances the foaming and foam stabilizing ability of shampoos.

(2) By thickening the shampoo system with a specific amino acid thickener, a good thickening effect can be achieved, the solution is transparent, and the produced pet shampoo has good stability even in repeated freeze-thaw tests. It overcomes the problem that anionic shampoos are difficult to thicken.

(3) The pet shampoo of the present invention treats body surface parasitic skin diseases, bacterial skin diseases and fungal skin diseases of pets by combining fipronil, an antifungal agent and an antibacterial agent. It can achieve the purpose of prevention and treatment.

The invention is further described below in conjunction with specific embodiments, which are not intended to limit the invention in any way. Unless otherwise specified, the reagents, methods and devices used in the present invention are conventional reagents, methods and devices in the art.

All reagents and materials used in the following examples are commercially available unless otherwise stated.

Example 1 Shampoo with Antibacterial Function and Treating Ectoparasitic Skin Diseases in Pets This example provides 100g of a shampoo with antibacterial and treating skin diseases caused by pet ectoparasites. of each component by weight of
2 g fipronil, 1 g ketoconazole, 1 g benzalkonium bromide, 6 g alkyl glucoside (APG), 25 g cocamidopropyl betaine (CAB), 6 g dodecyldimethylamine oxide, 1 g cetearyl glucoside, disodium ethylenediaminetetraacetate (EDTA-2Na) 0.1 g, 0.1 g aminosilicone oil microemulsion, 0.01 g potassium sorbate, balance deionized water.

The method for producing the animal shampoo having the antibacterial function includes:
Add 35 mL of deionized water to a beaker and heat to 60° C., then add the alkyl glucoside, cocamidopropyl betaine and dodecyldimethylamine oxide to the deionized water and stir to dissolve, and after complete dissolution, add fipronil. After the fipronil is completely dissolved, add ketoconazole, stir while heating to maintain the temperature at 70 ° C. to dissolve, add amino silicone oil microemulsion after ketoconazole is sufficiently dissolved, and add amino silicone oil. (1) stopping heating after the microemulsion has completely dissolved;
During the cooling process of step (1), EDTA-2Na is added and stirred to dissolve, and when cooled to 40° C., benzalkonium bromide is added and stirred to dissolve, and benzalkonium bromide is completely dissolved. After dissolving, add cetearyl glucoside and stir to dissolve. After cetearyl glucoside is completely dissolved, add potassium sorbate and the remaining deionized water, stir uniformly, and then dispense and store. and step (2).

Example 2 Shampoo with the function of treating ectoparasite skin diseases in pets and with antibacterial function This example provides 100g of a shampoo with the function of treating ectoparasite skin diseases in pets and with antibacterial function, of each component by weight of
1 g fipronil, 3 g miconazole nitrate, 3 g chlorhexidine diacetate hydrate, 15 g alkyl glucoside (APG), 20 g cocamidopropyl betaine (CAB), 10 g dodecyldimethylamine oxide, 5 g fatty alcohol polyglycol ether (VD-92), EDTA 1 g, 1 g water-soluble lanolin, 0.125 g sodium benzoate, balance deionized water.

The method for producing the animal shampoo having the antibacterial function includes:
Bring the total volume to 100 mL, add 35 mL of deionized water to the beaker, heat to 70° C., then add the alkyl glucoside, cocamidopropyl betaine and dodecyldimethylamine oxide to the deionized water and stir to dissolve completely. and then add fipronil. After fipronil is completely dissolved, miconazole nitrate is added and dissolved by stirring while heating to maintain 70°C. adding lanolin and stopping heating after the water-soluble lanolin is completely dissolved (1);
During the cooling process of step (1), EDTA is added and stirred to dissolve, and when cooled to 40° C., chlorhexidine diacetate hydrate is added and stirred to dissolve, and chlorhexidine diacetate hydrate is completely dissolved. After dissolving, add fatty alcohol polyglycol ether (VD-92) and stir to dissolve. After the fatty alcohol polyglycol ether is completely dissolved, add sodium benzoate and remove the remaining amount to 100 mL. and a step (2) of adding ionized water, stirring uniformly, dispensing and storing.

Example 3 Shampoo with Antibacterial Function and Treating Ectoparasitic Skin Diseases in Pets This example provides 100g of a shampoo with antibacterial and treating ectoparasitic skin diseases in pets. of each component by weight of
0.2 g fipronil, 2 g econazole nitrate, 2 g chlorhexidine gluconate, 10 g alkyl glucoside (APG), 30 g cocamidopropyl betaine (CAB), 10 g dodecyldimethylamine oxide, PEG-120 methylglucose dioleate (DOE-120)1. 5 g, EDTA-2Na 0.1 g, cetrimonium chloride 0.5 g, isothiazolinone 0.01 g, deionized water balance.

The method for producing the animal shampoo having the antibacterial function includes:
Bringing the total volume to 100 mL, add 35 mL of deionized water to the beaker, heat to 80° C., then add the alkyl glucoside, cocamidopropyl betaine and dodecyldimethylamine oxide to the deionized water and stir to dissolve completely. After the fipronil is completely dissolved, add the econazole nitrate, stir while heating to maintain the temperature at 80° C. to dissolve, and after the econazole nitrate is sufficiently dissolved, add the cetrimonium. adding the chloride and stopping heating after the cetrimonium chloride has completely dissolved (1);
During the cooling process of step (1), EDTA-2Na is added and stirred to dissolve, and when cooled to 40°C, chlorhexidine gluconate is added and stirred to dissolve, and after chlorhexidine gluconate is completely dissolved, Add PEG-120 methyl glucose dioleate and stir to dissolve, and after PEG-120 methyl glucose dioleate is completely dissolved, add isothiazolinone, add the remaining deionized water to make 100 mL, and mix uniformly. and a step (2) of dispensing and storing after stirring to .

Example 4 Shampoo with Antibacterial Function and Treating Ectoparasitic Skin Diseases in Pets This example provides 100 g of a shampoo with antibacterial and treating ectoparasitic skin diseases in pets. of each component by weight of
0.5 g fipronil, 2 g clotrimazole, 1 g triclosan, 5 g alkylglucoside (APG), 20 g cocamidopropyl betaine (CAB), 10 g dodecyldimethylamine oxide, thickener - SCC68 1 g, EDTA 0.1 g, amino silicone oil 0.1 g, sodium dehydroacetate 0.01 g, deionized water balance.

The method for producing the animal shampoo having the antibacterial function includes:
Bring the total volume to 100 mL, add 35 mL of deionized water to the beaker, heat to 70° C., then add the alkyl glucoside, cocamidopropyl betaine and dodecyldimethylamine oxide to the deionized water and stir to dissolve completely. and then add fipronil. After fipronil is completely dissolved, add clotrimazole and dissolve by stirring while heating to maintain 70 ° C. After clotrimazole is fully dissolved, Step (1) of adding aminosilicone oil and stopping heating after the aminosilicone oil is completely dissolved;
During the cooling process of step (1), EDTA is added and stirred to dissolve, and when cooling to 50° C., triclosan is added and stirred to dissolve, and after triclosan is completely dissolved, the thickener-SCC68 is added. Add and dissolve with stirring, and after the thickener-SCC68 has completely dissolved, add sodium dehydroacetate, add the remaining deionized water to make 100 mL, stir uniformly, and then dispense. and step (2) of storing the

Example 5 Shampoo with Antibacterial Function and Treating Ectoparasitic Skin Diseases in Pets This example provides 100g of a shampoo with antibacterial and treating ectoparasitic skin diseases in pets. of each component by weight of
Fipronil 0.1 g, fluconazole 1 g, polyhexamethylene biguanide 1 g, alkyl glucoside (APG) 5 g, cocamidopropyl betaine (CAB) 20 g, dodecyldimethylamine oxide 8 g, acrylic acid ester copolymer emulsion 1 g, EDTA-2Na 0. 1 g, cetrimonium chloride 1 g, isothiazolinone 0.01 g, deionized water balance.

The method for producing the animal shampoo having the antibacterial function includes:
Bringing the total volume to 100 mL, add 35 mL of deionized water to the beaker, heat to 80° C., then add the alkyl glucoside, cocamidopropyl betaine and dodecyldimethylamine oxide to the deionized water and stir to dissolve completely. After dissolving in , add fipronil, after fipronil is completely dissolved, add fluconazole and dissolve by stirring while heating to maintain 80 ° C. After fluconazole is sufficiently dissolved, add cetrimonium chloride. Additionally, after the cetrimonium chloride has completely dissolved, the heating is stopped (1);
During the cooling process of step (1), EDTA-2Na was added and stirred to dissolve, and when cooling to 50°C, polyhexamethylene biguanide was added and stirred to dissolve, and polyhexamethylene biguanide was completely dissolved. After that, add the acrylic acid ester copolymer emulsion and stir to dissolve. After the acrylic acid ester copolymer emulsion is completely dissolved, add isothiazolinone and add the remaining deionized water to make 100 mL. , and a step (2) of dispensing and storing after uniformly stirring.

Example 6 Fipronil Solvent Screening Although the insect repellent fipronil is sparingly soluble in water, it is soluble in organic solvents such as acetone that are harmful to pet skin, and these organic solvents cannot be added to pet shampoo systems. , provides a non-toxic, innovative surfactant compound formulation that can be applied to pet shampoo, and by dissolving fipronil, it not only solves the problem that fipronil is difficult to dissolve, but also solves the problem of foaming and foaming in shampoo systems. Settled.

1. Screening test of a single solvent that dissolves fipronil (1) Test method Weigh 0.2 g of fipronil, an insect repellent, control the temperature to 80 ° C. or less, and 20 g of each formulation solvent shown in Table 1 In addition, the solubility of the insect repellent fipronil was observed.

(2) Dissolution Results Table 2 shows the dissolution conditions of fipronil in a single solvent. It can be seen from Table 2 that some surfactants alone cannot dissolve fipronil. Fipronil is a poorly soluble substance, can be dissolved in some specific solvents in Table 1 above, but the dissolution effect of a single solvent is not favorable, all are slightly soluble in water, fipronil cannot be completely dissolved, The need for product mass could not be met, therefore multiple methods were explored to dissolve fipronil.

2. Composite screening test of two solvents that dissolve fipronil (1) Test method 0.2 g of fipronil, an insect repellent, was weighed, the temperature was controlled to 80 ° C. or less, and each formulation shown in Table 3 was tested. In addition to solvents, the solubility of the insect repellent fipronil was observed.

(2) Dissolution Results Table 4 shows the dissolution of fipronil by combining two solvents.

As can be seen from the dissolution status in Table 4, the APG and CAB complex, the APG and OB-2 complex, and the CAB and OB-2 complex can all dissolve the insect repellent fipronil rapidly and completely. Complex solvents of 3, 4 and 10 were unable to completely dissolve fipronil.

APG, CAB and OB-2 are all commonly used surfactants in cosmetics and are not fipronil-specific solvents. could be better dissolved.

3. Composite screening test of three kinds of solvents that dissolve fipronil (1) Test method Weigh 0.2 g of fipronil, an insect repellent, and control the temperature to 80 ° C. or less. In addition to solvents, the solubility of the insect repellent fipronil was observed.

(2) Dissolution Result 6 shows the situation of dissolving fipronil by combining three kinds of solvents.

As can be seen from the dissolution times in Table 6, the dissolution time of fipronil by combining the three solvents was much shorter than that of the two solvents. The solvent used in the present invention is not a dedicated solvent for fipronil, and the dissolution effect is not preferable either alone or in combination. The repellent could be quickly and completely dissolved.

Example 7 Shampoo Stability Test 1. Production of Shampoo The total weight of shampoo was 100g.

1, Example 3 produced Pet Shampoo 1.

2. It was Pet Shampoo 2 that was produced in Example 2.

3. The manufacturing method of pet shampoo is
Bring the total volume to 100 mL, add 35 mL of deionized water to a beaker, heat to 60-80° C., then add 10 g of alkyl glucoside, 20 g of cocamidopropyl betaine into the deionized water and stir to dissolve, After complete dissolution, add 0.2 g of fipronil, after fipronil is completely dissolved, add 1 g of ketoconazole, stir to dissolve while heating to maintain 60-80 ° C, and ketoconazole is sufficiently (1) adding 0.1 g of aminosilicone oil microemulsion after dissolving in and stopping heating after the aminosilicone oil is completely dissolved;
During the cooling process of step (1), add 0.1 g of EDTA-2Na and stir to dissolve; when cooling to 40-50° C., add 1 g of benzalkonium bromide and stir to dissolve; After the benzalkonium bromide is completely dissolved, add 1 g of PEG-120 methylglucose dioleate and stir to dissolve, and after the PEG-120 methylglucose dioleate is completely dissolved, add 0.01 g of sorbic acid. A step (2) of adding potassium, adding the remaining deionized water to make 100 mL, stirring uniformly, dispensing and storing to obtain pet shampoo 3 (2).

4. The manufacturing method of pet shampoo is
Bring the total volume to 100 mL, add 35 mL of deionized water to a beaker, heat to 60-80° C., then add 6 g of alkyl glucoside, 6 g of dodecyldimethylamine oxide into the deionized water and stir to dissolve; After completely dissolving, add 0.2 g of fipronil, after fipronil is completely dissolved, add 1 g of ketoconazole, stir while heating to maintain 60-80° C. to dissolve, and ketoconazole is fully dissolved. (1) adding 0.1 g of aminosilicone oil microemulsion after dissolving and stopping heating after the aminosilicone oil is completely dissolved;
During the cooling process of step (1), add 0.1 g of EDTA-2Na and stir to dissolve; when cooling to 40-50° C., add 1 g of benzalkonium bromide and stir to dissolve; After the benzalkonium bromide is completely dissolved, add 1 g of PEG-120 methylglucose dioleate and stir to dissolve, and after the PEG-120 methylglucose dioleate is completely dissolved, add 0.01 g of sorbic acid. A step (2) of adding potassium, adding the remaining deionized water to make 100 mL, stirring uniformly, dispensing and storing to obtain pet shampoo 4.

5. The manufacturing method of pet shampoo is
Bringing the total volume to 100 mL, add 35 mL of deionized water to a beaker, heat to 60-80° C., then add 20 g of cocamidopropyl betaine, 6 g of dodecyldimethylamine oxide into the deionized water and stir to dissolve. After the fipronil is completely dissolved, add 0.2 g of fipronil. After the fipronil is completely dissolved, add 1 g of ketoconazole, stir while heating to maintain the temperature of 60-80° C., and dissolve the ketoconazole. (1) adding 0.1 g of aminosilicone oil microemulsion after is fully dissolved and stopping heating after the aminosilicone oil is completely dissolved;
During the cooling process of step (1), add 0.1 g of EDTA-2Na and stir to dissolve; when cooling to 40-50° C., add 1 g of benzalkonium bromide and stir to dissolve; After the benzalkonium bromide is completely dissolved, add 1 g of PEG-120 methylglucose dioleate and stir to dissolve, and after the PEG-120 methylglucose dioleate is completely dissolved, add 0.01 g of sorbic acid. a step (2) of adding potassium, adding the remaining deionized water to make 100 mL, stirring uniformly, dispensing and storing to obtain pet shampoo 5;

2. Shampoo Stability Evaluation (1) Test Method Foam Volume: Agitation Method. 0.5 g of each of the 5 shampoo samples produced in step 1 was weighed and placed in a 100 mL graduated cylinder, 20 mL of pure water was added, and the volume of the foam was read after 1 min. rice field.
Stability test: The prepared formulation samples were allowed to stand at room temperature, and the precipitation time was statistically determined.

(2) Test results

As can be seen from the results of the stability test in Table 7, the composite system of three surfactants had a good solubilizing effect on fipronil. By comparison, Shampoos 3 to 5, all of which are composites of two surfactants, had a low effect of dissolving miconazole nitrate, and the volumes of deposits and foams were small. As can be seen, the combination of the three surfactants was beneficial to the shampoo system and could also make the shampoo system more stable.

Example 8 Screening Test for Thickeners Currently, the general shampoo systems on the market are anionic, but most of the antibacterial agents added to the formulations are cationic surfactants. There was a cationic surfactant. Therefore, by using the non-anionic surfactant selected in the present invention as the main surfactant, there is a problem that it is difficult to thicken the shampoo system. The test of this example selects some common thickeners and some special thickeners, thickens the shampoo, and compares them by test to screen the optimum thickener. .

1. Shampoo preparation was the same as in Example 3. The difference between each shampoo is that the added thickening agent is different, which is specifically shown in Table 8.

2. Test results (1) Thickening effect: The shampoo was allowed to stand to remove air bubbles on the surface, and after defoaming, the viscosity was measured with a viscometer. The shampoo was allowed to stand and the transparency after defoaming was observed.

As can be seen from the test results in Table 8, the shampoos 2, 3, and 4 produced with the three high-molecular-weight polymer-based thickeners have sufficient viscosity, but the shampoo as a whole is not transparent. The use of thickeners was not considered. Salts such as sodium chloride had no obvious thickening effect and tended to precipitate, thus affecting the clarity and stability of the solution. Amino acid thickeners and some other thickeners have a certain thickening effect, but the viscosity of amino acid thickeners is the best, among which amino acid thickeners are cetearyl glucoside, acrylic acid ester There was a copolymer emulsion (SF-1), thickener-SCC68, fatty alcohol polyglycol ether (VD-92), PEG-120 methylglucose dioleate (DOE-120). The amino acid thickener can thicken the amino acid surfactant system, which is difficult to thicken, but the thickening effect of other systems is not clear. It has been found that it can also work well in non-anionic surfactant systems.

(2) Repeated freeze-thaw stability test Shampoo samples 1, 5-9, 11 prepared in Table 8 above and added with different thickeners, and a blank control sample with no added thickener -20 C. condition for 2 d, taken out and left for 2 d under 40.degree. C. accelerated condition. The stability status of the drugs in the formulation was inferred by detecting changes in the content of each drug by high performance liquid chromatography, sampling at each cycle, repeating three times.

From the test results in Table 9, it was found that formulations 5, 7 and 9 not only had high viscosities, but also had small variations in content.

From the results in Table 10, it was found that the amino acid thickener not only thickens the shampoo system, which is difficult to thicken, but also has the effect of increasing the stability of the shampoo system.

Example 9 Screening and optimizing manufacturing process 1. Screening test for optimal temperature of fipronil dissolution of each component by weight of
0.2 g fipronil, 2 g econazole nitrate, 2 g chlorhexidine gluconate, 10 g alkyl glucoside (APG), 30 g cocamidopropyl betaine (CAB), 10 g dodecyldimethylamine oxide, PEG-120 methylglucose dioleate (DOE-120)1. 5 g, EDTA-2Na 0.1 g, cetrimonium chloride 0.5 g, isothiazolinone 0.01 g, deionized water balance.

The method for producing the animal shampoo having the antibacterial function includes:
With a total volume of 100 mL, add 35 mL of deionized water to the beaker and heat to 30° C., 40° C., 50° C., 60° C., 70° C., 80° C., 90° C., respectively, according to the temperature of each process in Table 11; Alkyl glucoside, cocamidopropyl betaine and dodecyldimethylamine oxide are then added to deionized water and dissolved by stirring; after complete dissolution, fipronil is added; after fipronil is completely dissolved, econazole nitrate is added. , Stir and dissolve while heating to maintain each temperature, add cetrimonium chloride after econazole nitrate is sufficiently dissolved, and stop heating after cetrimonium chloride is completely dissolved Step (1) and,
During the cooling process of step (1), EDTA-2Na is added and stirred to dissolve, and when cooled to 40°C, chlorhexidine gluconate is added and stirred to dissolve, and after chlorhexidine gluconate is completely dissolved, Add PEG-120 methyl glucose dioleate and stir to dissolve, and after PEG-120 methyl glucose dioleate is completely dissolved, add isothiazolinone, add the remaining deionized water to make 100 mL, and mix uniformly. and a step (2) of dispensing and storing after stirring to .

As can be seen from the results of the temperature screening test, the dissolution time is short at 70-80°C conditions, 80°C is optimal, and the viscosity at 90°C is almost the same as at 70°C, but lower than 80°C. The higher the temperature, the higher the cost. The optimal temperature was therefore 80°C.

2. Optimization of raw material supply order The shampoo formulation and parameter conditions were the same as in Process 6 above.

Process 8:
(1-1) Make the total volume 100 mL, add 35 mL of deionized water to a beaker, heat to 80 ° C., first add the prescribed amount of fipronil, then add the prescribed amount of alkyl glucoside, and heat for 10 minutes. After stirring while stirring, cocamidopropyl betaine and dodecyldimethylamine oxide are added and dissolved by stirring, and after complete dissolution, econazole nitrate is added and dissolved by stirring while heating to maintain 80 ° C. After the econazole nitrate was fully dissolved, cetrimonium chloride was added and heating was stopped after the cetrimonium chloride was completely dissolved.
(1-2) In the cooling process of step (1), EDTA-2Na is added and stirred to dissolve, and when cooled to 40°C, chlorhexidine gluconate is added and stirred to dissolve, and chlorhexidine gluconate is completely dissolved. , add PEG-120 methyl glucose dioleate and stir to dissolve, and after PEG-120 methyl glucose dioleate is completely dissolved, add isothiazolinone to make up to 100 mL. After adding water and uniformly stirring, the mixture was dispensed and stored.

(2) Process 9:
(1-1) Make the total volume 100 mL, add 35 mL of deionized water into a beaker, heat to 80 ° C., then add alkyl glucoside, heat and stir, add fipronil after complete dissolution, After heating and stirring for 10 minutes, cocamidopropyl betaine and cetrimonium chloride are added, and after heating and stirring for 10 minutes, dodecyldimethylamine oxide is added. After the econazole nitrate was sufficiently dissolved, the heating was stopped.
(1-2) In the cooling process of step (1), EDTA-2Na is added and stirred to dissolve, and when cooled to 40°C, chlorhexidine gluconate is added and stirred to dissolve, and chlorhexidine gluconate is completely dissolved. , add PEG-120 methyl glucose dioleate and stir to dissolve, and after PEG-120 methyl glucose dioleate is completely dissolved, add isothiazolinone to make up to 100 mL. After adding water and uniformly stirring, the mixture was dispensed and stored.

(3) The time from the addition of fipronil to complete dissolution and the viscosity of the entire shampoo were observed, and the statistical results are shown in Table 12.

Example 10 Clinical therapeutic efficacy test of parasitic skin diseases in pet dogs and cats 1. Test animals Spontaneous cases of parasitic skin diseases were selected from dogs and cats of Xinglei Migao Pet Farm in Yunfu City, Guangdong Province. A total of 40 animals were selected. Of these, 20 were dogs and 20 were cats.

2. Test method (1) Clinical examination: Whole-body clinical examination was carried out, including normal indexes such as body temperature, respiration, and heart rate. 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 were examined topically.

(2) Examination of ectoparasites: The affected skin was collected, observed under a microscope, and the number of ectoparasites in the local lesion was calculated. In the case of flea infestation: the number of fleas, the distribution and number of flea droppings were calculated and statistically calculated. Dermatitis caused by tick bites: The number of ticks and skin damage were calculated and statistics were obtained.

(3) Medication method The hair of a dog or cat was wetted with water, and the shampoo was applied all over the body, avoiding the eyes, nose and mouth. After washing and massaging, the product was allowed to come into contact with the skin and fur for 10 minutes. Washing with water and wearing an Elizabethan collar prevented dogs and cats from licking themselves and the foam during bathing. The test drug group was animals that used the shampoo of Example 3 twice a week and the amount of shampoo used each time was 1-2 mg/kg, and the blank group used no shampoo as a control.

(4) Evaluation index of therapeutic effect:
Efficacy: Mean reduction in ectoparasite counts on the skin was greater than 90% during and after dosing, with no itching, rashes, scales, or injury from test animal self-bites on the affected areas.

Ineffective: During and after drug treatment, the average reduction in the number of ectoparasites on the skin was less than 90%, and the affected area still had itching, rashes, scales, etc., and the damage caused by the animal's self-bite was evident. there were.

Recurrence Rate Monitoring: Post-healing dogs and cats were monitored for clinical signs of skin and number of skin parasites within 1 week after drug cessation.

3. Test results (1) Evaluation results of therapeutic effects

3. Test results As can be seen from Table 13, the pet shampoo of the present invention has a cure rate of 100% for dogs with parasitic skin diseases, and a cure rate of 90% for cats with parasitic skin diseases. % reached.

(2) Recurrence rate monitoring results Observed within 1 week after stopping medication, 10 dogs with parasitic skin disease in the treatment group of the study showed no recurrence after healing. , of 9 cats with parasitic skin disease, 1 relapsed after healing. From the above, it was found that after using the shampoo of the present invention, the parasites on the body surface of the pet can be effectively repelled, and the pet is freed from the problem of parasites.

Example 10 Clinical efficacy test of fungal skin disease in pet dogs and cats 1. Test animal Total spontaneous cases of fungal skin disease from dogs and cats in Xinglei Migao Pet Farm, Yunfu City, Guangdong Province. 40 selected. Of these, 20 were dogs and 20 were cats.

2. Test method (1) Clinical examination: Whole body clinical examination and local clinical examination, and necessary skin smear examination were performed.

(2) Microbiological examination: samples were collected from the affected areas of the case animals, pathogens were isolated and identified, and finally pathogens were counted.

(3) Medication method The hair of a dog or cat was wetted with water, and the shampoo was applied all over the body, avoiding the eyes, nose and mouth. After washing and massaging, the product was allowed to come into contact with the skin and fur for 10 minutes. Washing with water and wearing an Elizabethan collar prevented dogs and cats from licking themselves and the foam during bathing. The test drug group (Shampoo of Example 3) was used twice a week, with animals receiving 1-2 mg/kg of shampoo each time, and the blank group received no shampoo as a control.

(4) Evaluation index of therapeutic effect Healing: After administration, the negative rate of isolated pathogenic fungi on the skin is 80% or more, the inflammatory secretion has largely disappeared, and the affected area has odor, rash, crust, and pus. The symptoms of itching have largely disappeared.

Efficacy: After administration, the isolated pathogenic fungus on the skin has a negative rate of 60% or more, the inflammatory discharge is reduced, the affected area has little odor, and rashes, scales, pustules, etc. are reduced. Itching symptoms were relieved.

Ineffective: After administration, the isolated pathogenic fungus rate of the skin is less than 60%, and inflammatory discharge is still present, and the affected area still has odor, rash, crust, pus, etc., and the affected area still had obvious symptoms of itching.

(5) Surveillance of recurrence rate: Clinical skin symptoms and skin microbiological examination were performed within 1 week after drug withdrawal in post-healing dogs and cats.

3. Test results (1) Evaluation results of therapeutic effects

From Table 14, it can be seen that the pet shampoo of the present invention has a healing rate of up to 90% for dogs and cats suffering from fungal skin diseases.

(2) Observation results of recurrence rate Observed within 1 week after stopping the drug, in the treatment group of the study, 9 dogs with fungal skin disease showed no recurrence after healing. , of nine cats with fungal skin disease, one relapsed after healing. From the above, it was found that after using the shampoo of the present invention, fungal skin diseases in pets can be effectively improved, and the recurrence rate is low.

Example 11 Clinical therapeutic efficacy test for bacterial skin diseases in pet dogs and cats 1. Test animals A total of 40 cases of spontaneous bacterial skin diseases from dogs and cats in Xinglei Migao Pet Farm, Yunfu City, Guangdong Province. selected a pair. Of these, 20 were dogs and 20 were cats.

2. Test method (1) Clinical examination: Whole body clinical examination, local clinical examination, and necessary skin smear examination (2) Microbiological examination: Collect samples from the affected area of the case animal, isolate the pathogen identified and finally counted pathogens.

(3) Medication method The hair of a dog or cat was wetted with water, and the shampoo was applied all over the body, avoiding the eyes, nose and mouth. After washing and massaging, the product was allowed to come into contact with the skin and fur for 10 minutes. Washing with water and wearing an Elizabethan collar prevented dogs and cats from licking themselves and the foam during bathing. The test drug group (Shampoo of Example 3) was used twice a week, with animals receiving 1-2 mg/kg of shampoo each time. A blank group used no shampoo as a control.

(4) Evaluation index of therapeutic effect Healing: After administration, the negative rate of isolated pathogenic bacteria on the skin is 80% or more, the inflammatory secretion has largely disappeared, and the affected area has odor, rash, crust, and pus. The symptoms of itching have largely disappeared.

Efficacy: After administration, the negative rate of isolated pathogenic bacteria on the skin is 60% or more, the inflammatory secretion is reduced, the affected area has little odor, rashes, crusts, pustules, etc. are reduced, Itching symptoms were relieved.

Ineffective: After administration, the isolated pathogenic fungus rate of the skin is less than 60%, and inflammatory discharge is still present, and the affected area still has odor, rash, crust, pus, etc., and the affected area still had obvious symptoms of itching.

(5) Surveillance of recurrence rate: Clinical skin symptoms and skin microbiological examination were performed within 1 week after drug withdrawal in post-healing dogs and cats.

3. Test results (1) Evaluation results of therapeutic effects

From Table 15, it can be seen that the pet shampoo of the present invention can reach a cure rate of 90% for dogs with bacterial skin diseases and a cure rate of 100% for cats with bacterial skin diseases.

(2) Monitoring results of recurrence rate Observed within 1 week after stopping the drug, in the treatment group of the test, 9 dogs with bacterial skin disease showed no recurrence after healing Ten cats with bacterial skin disease had no recurrence of bacterial skin disease after healing. From the above, it was found that after using the shampoo of the present invention, bacterial skin diseases in pets can be effectively improved, and the recurrence rate is low.

Finally, it should be mentioned that the above embodiments are only for describing the technical solutions of the present invention, and not for limiting the protection scope of the present invention. Other different changes and modifications may be made to the embodiments, and it is not necessary to cover all embodiments here. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall all fall within the protection scope of the claims of the present invention.

Claims (6)

A pet shampoo having the function of treating skin diseases caused by ectoparasites and antibacterial,
0.1 to 2 parts fipronil, 1 to 5 parts antifungal , 1 to 5 parts antibacterial, 5 to 15 parts alkyl glucoside, 20 to 30 parts cocamide, with a total weight of 100 parts. Propyl betaine, 2-10 parts dodecyldimethylamine oxide, 1-10 parts thickener, 0.1-2 parts chelating agent, 0.1-5 parts conditioner, 0.01-1 part preservative agent,
the antifungal agent is one or more of ketoconazole, econazole nitrate, miconazole nitrate, clotrimazole, fluconazole;
the antibacterial agent is one or more of benzalkonium chloride, benzalkonium bromide, chlorhexidine diacetate hydrate, chlorhexidine gluconate, triclosan, polyhexamethylene biguanide;
the conditioner is one or more of cetrimonium chloride, water-soluble lanolin, aminosilicone oil, aminosilicone oil microemulsion;
the preservative is one or more of potassium sorbate, sodium dehydroacetate, sodium benzoate, isothiazolinone, balance deionized water,
A pet shampoo characterized by: 0.2 to 2 parts fipronil, 1 to 3 parts antifungal, 1 to 3 parts antibacterial, 6 to 15 parts alkyl glucoside, 20 to 30 parts cocamide, with a total weight of 100 parts Propyl betaine, 6-10 parts dodecyldimethylamine oxide, 1-5 parts thickener, 0.1-1 part chelating agent, 0.1-1 part conditioner, 0.01-0.125 parts preservative, balance deionized water. 2. The pet shampoo according to claim 1, wherein the weight ratio of said alkyl glucoside, cocamidopropyl betaine and dodecyldimethylamine oxide is 10-15:20-30:10. 2. The method according to claim 1, wherein the thickening agent is one or more of cetearyl glucoside, acrylate copolymer emulsion , fatty alcohol polyglycol ether, and PEG-120 methylglucose dioleate. Pet shampoo as described. 2. The pet shampoo according to claim 1, wherein the chelating agent is one or more of ethylenediaminetetraacetic acid and disodium ethylenediaminetetraacetic acid. First, deionized water, which accounts for 35% of the total volume of the shampoo, is heated to 60-80°C, then the alkyl glucoside, cocamidopropyl betaine and dodecyldimethylamine oxide are added to the deionized water and stirred to dissolve, After complete dissolution, fipronil is added. After fipronil is completely dissolved, the antifungal agent is added and dissolved by stirring while heating to maintain 60 to 80 ° C. until the antifungal agent is sufficiently dissolved. (1) adding a conditioner and stopping heating after the conditioner has completely dissolved;
After stopping heating in step (1), the chelating agent is added and stirred to dissolve, and when cooled to 40-50 ° C., the antibacterial agent is added and stirred to dissolve, and the antibacterial agent is completely dissolved. After dissolving, the thickener is added and stirred to dissolve, and after the thickener is completely dissolved, the preservative and the remaining deionized water are added and uniformly stirred to obtain step (2). 6. The method for producing a pet shampoo according to any one of claims 1 to 5 , comprising: