WO2022110487A1

WO2022110487A1 - Pet shampoo with functions of treating ectoparasite skin diseases and resisting microbia and preparation method therefor

Info

Publication number: WO2022110487A1
Application number: PCT/CN2020/141173
Authority: WO
Inventors: 焦晓军; 辜质纯; 崔兴龙; 徐奇清
Original assignee: 佛山市南海东方澳龙制药有限公司
Priority date: 2020-11-27
Filing date: 2020-12-30
Publication date: 2022-06-02
Also published as: CN112426373B; JP2022551208A; CN112426373A; JP7271014B2

Abstract

A pet shampoo with the functions of treating ectoparasite skin diseases and resisting microbia and a preparation method therefor. An insect-expelling ingredient fipronil is added to the pet shampoo; the problem of the fipronil being insoluble is solved by means of compounding a specific surfactant system; and moreover, the compounded surfactant system also has thickening, foaming and foam stabilization effects. Furthermore, the anionic shampoo system is thickened by a specific amino acid thickener, so that a good thickening effect can be achieved, the shampoo system reaches ideal consistency, and the product is stable. The combination of the three ingredients of the fipronil, antifungal agent and antibacterial agent can effectively prevent and treat common pet body surface parasitic, bacterial and fungal skin diseases.

Description

A kind of pet shampoo with treatment of external parasitic skin diseases and antibacterial function and preparation method thereof

technical field

The invention relates to the field of pet daily cosmetic detergents, in particular to a pet shampoo with functions of treating external parasitic skin diseases and antibacterial and a preparation method thereof.

Background technique

In recent years, dog and cat skin disease is one of the most common clinical diseases. Pet skin diseases are frequently-occurring diseases, which can cause pet skin itching, hair loss, redness, swelling, scabs, etc., with great harm and high incidence. There are many types of pet skin diseases, parasitic skin diseases and fungal skin diseases are the most common. Pet dog parasitic skin diseases mainly include skin diseases caused by Demodex mites, scabies mites, ear itching mites, dermatitis caused by the bites of fleas, lice, ticks, etc., as well as hookworm larval dermatitis, microfilariae of canine heartworm Dermatitis, etc. Pet bacterial skin disease pyoderma is sometimes secondary to infection from demodicosis, lacerations, wounds, burns, or dermatitis. Skin diseases caused by fungal infections also account for a considerable proportion, especially in hot and rainy summer. The etiology of the disease is complex, difficult to diagnose, difficult to treat, and has a high recurrence rate. Over-intensive breeding of pets, abuse of antibiotics, unreasonable nutritional intake, and abuse of human shampoo on pets are all reasons for the increase in the incidence of canine dermatophytosis.

Since most pet skin diseases can be qualitatively observed by the naked eye, for local pet skin problems, shampoo therapy can restore the normal microenvironment of the skin surface by removing allergens, microorganisms, reducing irritation and eliminating infection, bringing it to pets Soft, shiny, manageable hair. The Chinese invention patent with the publication number of CN108553335A provides a medicinal shampoo with the functions of preventing and treating pet skin diseases and a preparation method thereof. Effective, but not a good treatment for parasitic skin diseases.

Fipronil is a new type of benzopyrazole insecticide, which is a kind of drug suitable for killing ectoparasites of pets such as dogs and cats. It has the characteristics of broad spectrum and high efficiency, and has been widely used in many In the agricultural field, it is an important insecticide, but fipronil is insoluble in water and easily soluble in organic solvents such as acetone. According to the "Safety Technical Specification for Cosmetics" in organic solvents such as acetone, it cannot be used in cosmetics and pet shampoos. Therefore, how to effectively dissolve fipronil in a shampoo system to prepare a pet shampoo with stable system, ideal consistency, and at the same time with deworming, antifungal, and antibacterial properties, for the prevention and treatment of common pet body surface Parasitic, bacterial and fungal skin diseases are of considerable necessity.

technical solutions

The present invention aims to provide a pet shampoo with functions of treating external parasitic skin diseases and antibacterial and a preparation method thereof. The shampoo is added with the insect repellent ingredient Feprednisolone, and the compounded specific surfactant system solves the problem of insoluble Feprelonil, and the compounded surfactant system also has the effect of thickening and foaming and stabilizing the foam; In addition, the anionic shampoo system is thickened by a specific amino acid thickener, which can achieve a good thickening effect, make the shampoo system achieve an ideal consistency, and the product is stable; The combination of the three components of the bacterial agent can effectively prevent and treat common pet body surface parasitic, bacterial and fungal skin diseases.

The primary purpose of the present invention is to provide a pet shampoo with the functions of treating external parasitic skin diseases and antibacterial.

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

The above-mentioned purpose of the present invention is achieved by the following technical solutions:

The invention provides a pet shampoo with functions of treating external parasitic skin diseases and antibacterial. The total mass part is calculated as 100 parts and comprises the following components: 0.1-2 parts of fipronil, 1-5 parts of antifungal agent , 1 to 5 parts of antibacterial agent, 5 to 15 parts of alkyl glycoside (APG), 20 to 30 parts of cocamidopropyl betaine (CAB), dodecyl dimethyl amine oxide (OB-2) 2 ~10 parts, 1-10 parts of thickener, 0.1-2 parts of chelating agent, 0.1-5 parts of conditioner, 0.01-1 part of preservative, and deionized water to make up.

In the pet shampoo provided by the present invention, as an insect repellant, fipronil can effectively expel fleas and ticks on the surface of pets and treat parasitic infections, but because fipronil is insoluble in water and easily soluble in acetone and other organic solvents. According to the "Cosmetic Safety Technical Specifications", acetone and other organic solvents cannot be used in cosmetics and pet shampoos. The present invention is compounded with specific surfactant systems: alkyl glycosides, alkyl glycosides (APG), cocamidopropyl Three kinds of surface active compound of betaine (CAB) and dodecyl dimethyl amine oxide (OB-2) can be used in shampoo system. Since the repellant for pets, fipronil, is insoluble in water, but is soluble in organic solvents such as acetone that are harmful to pet skin, these organic solvents cannot be added to the pet shampoo system. The pet shampoo has a non-toxic compound surfactant formula to dissolve fipronil, which not only solves the problem of insoluble fipronil, but also enhances the foaming and foam stability of the shampoo system.

The antibacterial components in the shampoo have good antibacterial and fungal infection effects, thereby preventing secondary infections caused by parasites; the present invention can combine the three components of an insect repellent, an antifungal agent and an antibacterial agent. Effectively prevent and treat common pet parasitic, bacterial and fungal skin diseases.

Preferably, the total mass part of the pet shampoo is based on 100 parts, including the following components: 0.2-2 parts of fipronil, 1-3 parts of antifungal agent, 1-3 parts of antibacterial agent, and 6 parts of alkyl glycosides. ~15 parts, 20-30 parts of cocamidopropyl betaine, 6-10 parts of dodecyl dimethyl amine oxide, 1-5 parts of thickener, 0.1-1 part of chelating agent, 0.1-1 part of conditioner parts, 0.01-0.125 parts of preservatives, supplemented by deionized water.

Preferably, the mass ratio of the alkyl glycoside alkyl glycoside, cocamidopropyl betaine and dodecyl dimethyl amine oxide is 10-15:20-30:10. Under this ratio, the fipronil repellent can be dissolved faster and more completely.

Preferably, the thickener is cetearyl glucoside, acrylate copolymer emulsion (SF-1), thickener-SCC68, fatty polyethylene glycol ether (VD-92), methyl glucose One or more of dioleate (DOE-120).

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

Since the shampoo system is generally an anionic system, and the antibacterial agent and conditioning agent added in the prescription are cationic surfactants, it causes the problem that the shampoo system is difficult to thicken, and the use of common polymer thickeners will exist. High temperature is easy to change color, low temperature is easy to jelly; inhibit the foam abundance of surfactants; skin feel is affected by polymer raw materials during cleaning, which is manifested as sticky, unclean, strong residual feeling; light viscosity decreases and other problems. Therefore, in order to overcome the above problems, the present invention thickens the shampoo by selecting a specific amino acid thickener, which can achieve a good thickening effect, the solution is clear and transparent, and the shampoo system can be more stable.

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

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

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

Preferably, the conditioning agent is one or more of cetrimonium chloride (1631), water-soluble lanolin, aminosilicone oil, and aminosilicone oil microemulsion.

Preferably, the preservative is one or more of potassium sorbate, sodium dehydroacetate, sodium benzoate, and cassone.

The present invention also provides the preparation method of above-mentioned pet shampoo, comprising the following steps:

(1) First, heat deionized water that accounts for 35% of the total volume of the shampoo to 60-80 °C, then add alkyl glycosides, cocamidopropyl betaine and dodecyl dimethyl amine oxide into deionized water and stir Dissolve, add fipronil after complete dissolution, add antifungal agent after fipronil is completely dissolved, keep stirring and dissolve under heating at 60-80 °C, add conditioning agent after antifungal agent is fully dissolved, wait for conditioning agent Stop heating after complete dissolution;

(2) After the heating is stopped in step (1), add a chelating agent and stir to dissolve. When cooled to 40-50 °C, add an antibacterial agent to stir and dissolve. After the antibacterial agent is completely dissolved, add a thickener to stir and dissolve. After completely dissolving, add preservatives and the balance of deionized water, and stir evenly.

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

According to the research of the present invention, it is found that the preparation process has obvious influence on the dissolving effect of fipronil, such as alkyl glycosides, cocopropyl betaine and dodecyl dimethyl amine oxide in step (1), conditioners The order of adding each raw material is not arbitrary. After adding the alkyl glycosides, cocamidopropyl betaine coconut oil, and dodecyl dimethyl amine oxide into deionized water, stirring and dissolving, then adding fipronil in turn. , antifungal and conditioning agents, fipronil dissolves faster and has a better consistency. In addition, the heating temperature also has a significant effect on the dissolution of fipronil. When the heating temperature is lower than 30 °C, the fipronil cannot be dissolved at all, and when the heating temperature is 70-80 °C, not only the dissolution time is short, but the viscosity of the shampoo is relatively high. it is good.

The shampoo provided by the invention has the functions of treating pet ectoparasitic skin diseases and antibacterial functions, and the preparation process is simple and the operability is strong.

Compared with the prior art, the present invention has the following beneficial effects:

(1) By adding specific safe and non-toxic surfactant formulations: alkyl glycosides, cocamidopropyl betaine and dodecyl dimethyl amine oxide in the pet shampoo of the present invention, it not only solves the problem of nonprednisolone At the same time, it can enhance the foaming and stable foaming ability of the shampoo system.

(2) The shampoo system is thickened by a specific amino acid thickener, which can achieve a good thickening effect, the solution is clear and transparent, and the prepared pet shampoo still has good stability in repeated freezing and thawing experiments, overcoming The problem of difficult thickening of anionic shampoo systems.

(3) The pet shampoo of the present invention combines the three components of fipronil, antifungal agent and antibacterial agent, which can simultaneously achieve the purpose of preventing and treating pet parasites, bacteria and fungal skin diseases .

Embodiments of the present invention

The present invention is further described below in conjunction with specific embodiments, but the embodiments do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the technical field.

Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

Example 1 Shampoo with the function of treating pet ectoparasite skin diseases and antibacterial function

The present embodiment provides 100 g of shampoo with the function of treating pet ectoparasite skin disease and antibacterial function, which is composed of the following components by weight:

Fipronil 2 g, Ketoconazole 1 g, benzalkonium bromide 1 g, alkyl glycoside (APG) 6 g, cocamidopropyl betaine (CAB) 25 g, dodecyl dimethyl amine oxide 6 g, cetearyl glucoside 1 g, disodium ethylenediaminetetraacetate (EDTA-2Na) 0.1 g, amino silicone oil microemulsion 0.1 g, potassium sorbate 0.01 g, and the rest of the deionized water.

The preparation method of the above-mentioned animal shampoo with antibacterial function is:

(1) Add 35 mL of deionized water to the beaker and heat it to 60°C, then add the alkyl glycoside, cocamidopropyl betaine and dodecyl dimethyl amine oxide into the deionized water and stir to dissolve, completely. After dissolving, add fipronil, add ketoconazole after fipronil is completely dissolved, keep stirring at 70°C to dissolve, add amino silicone oil microemulsion after ketoconazole is fully dissolved, and wait until amino silicone oil microemulsion is completely Stop heating after dissolving;

(2) During the cooling process of step (1), add EDTA-2Na and stir to dissolve. When cooled to 40°C, add benzalkonium bromide and stir to dissolve. After benzalkonium bromide is completely dissolved, add cetearyl glucoside and stir to dissolve. , after the cetearyl glucoside is completely dissolved, add potassium sorbate and the remaining amount of deionized water, stir evenly, and then pack and store.

Example 2 Shampoo with the function of treating pet ectoparasite skin diseases and antibacterial function

The present embodiment provides 100 g of shampoo with the function of treating pet ectoparasite skin disease and antibacterial function, which is made up of the following components by weight:

Fipronil 1 g, Miconazole Nitrate 3 g, 3 g of chlorhexidine acetate, 15 g of alkyl glycosides (APG), 20 g of cocamidopropyl betaine (CAB), 10 g of dodecyl dimethyl amine oxide, fatty polyethylene glycol ether (VD -92) 5 g, 1 g of EDTA, 1 g of water-soluble lanolin, 0.125 g of sodium benzoate, and the rest of the deionized water.

(1) Calculated based on the total volume of 100 mL, add 35 mL of deionized water to the beaker, heat it to 70 °C, and then add alkyl glycosides, cocamidopropyl betaine and dodecyl dimethyl amine oxide to the beaker. Stir and dissolve in deionized water, add fipronil after complete dissolution, add miconazole nitrate after fipronil is completely dissolved, keep stirring and dissolve under heating at 70 °C, and add water-soluble after miconazole nitrate is fully dissolved Lanolin, stop heating after the water-soluble lanolin is completely dissolved;

(2) During the cooling process of step (1), add EDTA and stir to dissolve. When cooled to 40°C, add chlorhexidine acetate and stir to dissolve. After chlorhexidine acetate is completely dissolved, add fatty polyethylene glycol ether (VD-92) Stir to dissolve, add sodium benzoate after the fatty polyethylene glycol ether is completely dissolved, and make up the rest with deionized water, stir evenly, and then pack and store.

Example 3 Shampoo with the function of treating pet ectoparasite skin diseases and antibacterial function

Fipronil 0.2 g, Econazole Nitrate 2 g, Chlorhexidine Gluconate 2 g, Alkyl Glycosides (APG) 10 g, Cocamidopropyl Betaine (CAB) 30 g, Dodecyl Dimethyl amine oxide 10g, methylglucodioleate (DOE-120) 1.5g, EDTA-2Na 0.1g, cetrimonium chloride 0.5g, cassone 0.01g, and the rest of the deionized water.

(1) Calculated based on the total volume of 100 mL, add 35 mL of deionized water to the beaker, heat it to 80 °C, and then add the alkyl glycoside, cocamidopropyl betaine and dodecyl dimethyl amine oxide to the beaker. Stir and dissolve in deionized water, add fipronil after complete dissolution, add econazole nitrate after fipronil is completely dissolved, keep stirring and dissolve under heating at 80 °C, and add cetroxil after econazole nitrate is fully dissolved Ammonium chloride, stop heating after cetrimonium chloride is completely dissolved;

(2) During the cooling process of step (1), add EDTA-2Na and stir to dissolve. When cooled to 40°C, add chlorhexidine gluconate and stir to dissolve. After chlorhexidine gluconate is completely dissolved, add methylglucaric dioleic acid. The ester is stirred to dissolve, and after the methyl glucose dioleate is completely dissolved, add Cassone, and the rest is made up with deionized water. After stirring evenly, it can be stored in separate packages.

Example 4 Shampoo with the function of treating pet ectoparasite skin diseases and antibacterial function

Fipronil 0.5g, Clotrimazole 2 g, triclosan 1 g, alkyl glycoside (APG) 5 g, cocamidopropyl betaine (CAB) 20 g, dodecyl dimethyl amine oxide 10 g, thickener-SCC68 1 g, EDTA 0.1 g, amino silicone oil 0.1 g, sodium dehydroacetate 0.01 g, and the rest are deionized water.

(1) Calculated based on the total volume of 100 mL, add 35 mL of deionized water to the beaker, heat it to 70 °C, and then add alkyl glycosides, cocamidopropyl betaine and dodecyl dimethyl amine oxide to the beaker. Stir and dissolve in deionized water, add fipronil after complete dissolution, add clotrimazole after fipronil is completely dissolved, keep stirring and dissolve under heating at 70 °C, add amino silicone oil after clotrimazole is fully dissolved, and wait for Stop heating after the amino silicone oil is completely dissolved;

(2) During the cooling process of step (1), add EDTA and stir to dissolve. When cooled to 50 °C, add triclosan and stir to dissolve. After the triclosan is completely dissolved, add thickener-SCC68 to stir and dissolve. After the thickener- After the SCC68 is completely dissolved, add sodium dehydroacetate and make up the rest with deionized water, stir evenly, and then pack and store.

Example 5 Shampoo with the function of treating pet ectoparasite skin diseases and antibacterial function

Fipronil 0.1 g, Fluconazole 1 g, Polyhexamethylene biguanide 1 g, alkyl glycoside (APG) 5 g, cocamidopropyl betaine (CAB) 20 g, dodecyl dimethyl amine oxide 8 g, acrylate copolymer emulsion 1 g, EDTA-2Na 0.1 g, Western Trichloramine 1 g, Kasone 0.01 g, and the rest are deionized water.

(1) Calculated based on the total volume of 100 mL, add 35 mL of deionized water to the beaker, heat it to 80 °C, and then add the alkyl glycoside, cocamidopropyl betaine and dodecyl dimethyl amine oxide to the beaker. Stir and dissolve in deionized water, add fipronil after complete dissolution, add fluconazole after fipronil is completely dissolved, keep stirring and dissolve under heating at 80 °C, and add cetrimonium chloride after fluconazole is fully dissolved , stop heating after cetrimonium chloride is completely dissolved;

(2) During the cooling process of step (1), add EDTA-2Na and stir to dissolve. When cooled to 50 °C, add polyhexamethylene biguanide to stir and dissolve. After the polyhexamethylene biguanide is completely dissolved, add acrylate copolymer emulsion. Stir to dissolve, add Cassone after the acrylate copolymer emulsion is completely dissolved, and make up the rest with deionized water. After stirring evenly, it can be stored in separate packages.

Example 6 Fipronil Solvent Screening

Since the repellant fipronil is insoluble in water, it is soluble in organic solvents such as acetone, which are harmful to pet skin, and these organic solvents cannot be added to the pet shampoo system. The non-toxic compound surfactant formula to dissolve fipronil not only solves the problem of insoluble fipronil, but also solves the problem of foaming and stable foaming of the shampoo system.

1. Single-solvent dissolving fipronil screening test

(1) Experimental method

Weigh 0.2 g of the insect repellant fipronil, and add 20 g of each formulation solvent shown in Table 1 under the temperature control of 80° C. to observe the degree of dissolution of the insect repellant fipronil.

Table 1

(2) Dissolution results

The situation of dissolving Fipronil in a single solvent is shown in Table 2. It can be seen from Table 2 that some surfactants cannot dissolve Fipronil alone. Fipronil is an insoluble substance. Although it can be dissolved in some specific solvents, the dissolution effect of a single solvent is not ideal. They are all slightly soluble in water and cannot fully dissolve fipronil, which cannot meet the requirements of product quality. Therefore, the method of compounding is considered. to dissolve fipronil.

Table 2

2. Screening test of two kinds of solvents to dissolve fipronil

(1) Experimental method

Weigh 0.2 g of the repellant fipronil, and add it to each of the formulation solvents shown in Table 3 at a temperature of 80 °C to observe the degree of dissolution of the repellant fipronil.

table 3

(2) Dissolution results

Table 4 shows the situation of dissolving fipronil in two solvents.

Table 4

From the dissolution situation in Table 4, it can be seen that the combination of APG and CAB, the combination of APG and OB-2, and the combination of CAB and OB-2 can completely dissolve the insect repellant fipronil quickly, but prescription 3, 4 and 10 of the solvent composition cannot completely dissolve fipronil.

APG, CAB and OB-2 are surfactants commonly used in cosmetics, and are not special solvents for fipronil. However, it has been found that the surfactant compound system can better dissolve the insoluble component fipronil.

3. Screening test of three kinds of solvents to dissolve fipronil

(1) Experimental method

Weigh 0.2 g of the repellant fipronil, and add it to each of the formulation solvents shown in Table 5 under the temperature control of 80 °C to observe the degree of dissolution of the repellant fipronil.

table 5

(2) Dissolution results

Table 6 shows the situation of dissolving fipronil in three solvents.

Table 6

As can be seen from the dissolution time in Table 6, the time for dissolving Fipronil in three solvents is greatly shortened compared to the two solvents, although the solvent used in the present invention is not a special solvent for Fipronil, and the single use and The compounding and dissolving effect of the two is not good, but in the present invention, the three are compounded in an appropriate ratio, and the insoluble substance non-prednisolone insect repellant can be dissolved quickly and completely.

Example 7 Shampoo Stability Test

1. Preparation of shampoo

Calculated on a total weight of 100 g of shampoo.

1. The pet shampoo 1 prepared in Example 3 is pet shampoo 1.

2. The pet shampoo 2 prepared in Example 2 is pet shampoo 2.

3. The preparation method of pet shampoo is:

(1) Calculated based on the total volume of 100 mL, add 35 mL of deionized water to the beaker, and heat it to 60-80 °C, then add 10 g of alkyl glycosides and 20 g of cocamidopropyl betaine into deionized water and stir to dissolve , add 0.2 g of fipronil after it is completely dissolved, add 1 g of ketoconazole after the fipronil is completely dissolved, keep stirring and dissolve under heating at 60-80 °C, and add 0.1 g of amino acid after the ketoconazole is fully dissolved. Silicone oil microemulsion, stop heating after amino silicone oil is completely dissolved;

(2) During the cooling process of step (1), add 0.1 g of EDTA-2Na and stir to dissolve. When cooled 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 methyl methyl bromide. Gluconate dioleate is stirred and dissolved, and after methyl glucose dioleate is completely dissolved, 0.01 g of potassium sorbate is added, and the rest is made up with deionized water.

4. The preparation method of pet shampoo is:

(1) Calculated based on the total volume of 100 mL, add 35 mL of deionized water to the beaker, and heat it to 60-80 °C, then add 6 g of alkyl glycosides and 6 g of dodecyl dimethyl amine oxide into the deionized water. Stir to dissolve, add 0.2 g of fipronil after complete dissolution, add 1 g of ketoconazole after fipronil is completely dissolved, keep stirring and dissolve under heating at 60-80 °C, and add 0.1 g of ketoconazole after fully dissolved g amino silicone oil microemulsion, stop heating after the amino silicone oil is completely dissolved;

5. The preparation method of pet shampoo is:

(1) Calculated according to the total volume of 100 mL, add 35 mL of deionized water to the beaker, and heat it to 60-80 °C, then add 20 g of cocamidopropyl betaine and 6 g of dodecyl dimethyl amine oxide into the beaker. Stir and dissolve in deionized water, add 0.2 g of fipronil after complete dissolution, add 1 g of ketoconazole after fipronil is completely dissolved, keep stirring and dissolve under heating at 60-80 °C, and wait until ketoconazole is fully dissolved Then add 0.1g amino silicone oil microemulsion, stop heating after the amino silicone oil is completely dissolved;

(2) During the cooling process of step (1), add 0.1 g of EDTA-2Na and stir to dissolve. When cooled 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 methyl methyl bromide. Gluconate dioleate is stirred and dissolved. After methyl glucose dioleate is completely dissolved, 0.01 g of potassium sorbate is added, and the rest is made up with deionized water.

2. Evaluation of shampoo stability

(1) Test method

Foam volume: by stirring method, weigh 0.5 g of the 5 shampoo samples prepared in step 1 into a 100 mL graduated cylinder, add 20 mL of pure water, shake uniformly 100 times, and read the foam volume at 1 min;

Stability test: The prepared prescription samples were placed at room temperature to count the precipitation time.

(2) Experimental results

Table 7

As can be seen from the results in Table 7, it can be seen from the results of the stability test that the three kinds of surface active compounds have a good solubilizing effect on fipronil, while the comparison shampoos 3 to 5 are all two kinds of surface active agents. Compounding, the effect of dissolving miconazole nitrate is poor and the precipitation and foam volume are also low. From this, it can be seen that the three types of rejuvenation are beneficial to the shampoo system, and can also make the shampoo system more stable.

Example 8 Thickener Screening Test

Since the common shampoo systems on the market are generally anionic systems, and most of the antibacterial agents added in the prescription are cationic surfactants, and the added conditioning agents also contain cationic surfactants, the non- As the main surfactant, anionic surfactants cause the problem that the shampoo system is difficult to thicken. In this example, some commonly used thickeners and some special thickeners were selected to thicken the shampoo, and compared through experiments Screen out the best thickener.

1. The preparation of shampoo is the same as in Example 3, and the difference of each shampoo is that the added thickener is different, as shown in Table 8.

2. Experimental results

(1) Thickening effect: Place the shampoo to eliminate surface air bubbles, and measure its viscosity on a viscometer after defoaming. And observe the clarity of the shampoo after defoaming.

Table 8

It can be seen from the experimental results in Table 8 that although the viscosity of the shampoo prepared by three kinds of polymer thickeners in shampoo 2, 3 and 4 is sufficient, the overall shampoo is not clear and transparent, so these two thickening agents Agents are not considered for use. Salts such as sodium chloride have less thickening effect and are more likely to precipitate out, thereby affecting the clarity and stability of the solution. The amino acid thickener and several other thickeners have a certain thickening effect, but the amino acid thickener has the best viscosity, among which the amino acid thickener includes cetearyl glucoside, acrylate copolymer emulsion (SF- 1), thickener-SCC68, fatty polyethylene glycol ether (VD-92), methyl glucose dioleate (DOE-120), amino acid thickener can make the amino acid surface active system that is difficult to thicken thicken. Thickening, but the thickening effect is not obvious in other systems, and the invention found that the amino acid thickener can also play a very good role in the special non-anionic surface active system of the patent invention.

(2) Repeated freeze-thaw stability test

The shampoo samples 1, 5-9, 11 prepared in the above table 8 with different thickeners and the blank control sample without thickener were first placed at -20 °C for 2d, and then taken out and accelerated at 40 °C. Condition placed for 2d. Three cycles were performed, and samples were taken in each cycle and the changes in the content of each drug were detected on a high-performance liquid chromatograph to infer the stability of the drugs in the prescription.

Table 9 Principal component content results of repeated freeze-thaw test

It can be seen from the experimental results in Table 9 that formulations 5, 7 and 9 not only have high viscosity but also have a small variation in content.

Table 10 Table of formula viscosity results of repeated freeze-thaw test (mPa•S)

It can be seen from the results in Table 10 that the amino acid thickener can not only thicken the refractory thickening shampoo system well but also have the effect of increasing the stability of the shampoo system.

Example 9 Preparation process screening and optimization

1. Screening test of optimal temperature for dissolving fipronil

(1) Calculated based on the total volume of 100 mL, add 35 mL of deionized water to the beaker, and heat it to 30 °C, 40 °C, 50 °C, 60 °C, 70 °C, 80 °C, 90 °C according to the temperature of each process in Table 11. ℃, then add alkyl glycoside, cocamidopropyl betaine and dodecyl dimethyl amine oxide into deionized water and stir to dissolve, and then add fipronil after complete dissolution, and after fipronil is completely dissolved Add econazole nitrate, keep stirring and dissolve under heating at various temperatures, add cetrimonium chloride after econazole nitrate is fully dissolved, and stop heating after cetrimonium chloride is completely dissolved;

Table 11 Results of the screening test for the optimal temperature for dissolving fipronil

"-" means insoluble

From the results of the temperature screening test, it can be seen that the dissolution time is shorter under the condition of 70~80℃, of which 80℃ is the best. Although the viscosity at 90℃ is similar to that of 70℃, the viscosity is lower than that at 80℃. The higher the temperature, the higher the cost. So the optimum temperature is 80°C.

2. Optimization of feeding sequence

The formula and parameter conditions of the shampoo are the same as the above-mentioned process 6.

(1) Process 8:

(1-1) Calculated according to the total volume of 100mL, add 35mL of deionized water to the beaker, heat it to 80°C, first add the prescribed amount of fipronil, then add the prescribed amount of alkyl glycosides, heat and stir for ten times. Add cocamidopropyl betaine and dodecyl dimethyl amine oxide and stir to dissolve, add econazole nitrate after complete dissolution, keep stirring and dissolve under heating at 80 °C, and add econazole nitrate after fully dissolved Cetrimonium chloride, stop heating after cetrimonium chloride is completely dissolved;

(1-2) During the cooling process of step (1), add EDTA-2Na and stir to dissolve. When cooled to 40 °C, add chlorhexidine gluconate and stir to dissolve. After the chlorhexidine gluconate is completely dissolved, add methylglucose two The oleic acid ester is stirred and dissolved. After the methyl glucose dioleate is completely dissolved, add Cassone, and the rest is made up with deionized water. After stirring evenly, it can be stored in separate packages.

(2) Process 9 :

(1-1) Calculated according to the total volume of 100 mL, add 35 mL of deionized water to the beaker, and heat it to 80 °C, then add the alkyl glycoside, heat and stir, completely dissolve, then add fipronil, and heat and stir for 10 minutes Then add cocamidopropyl betaine and cetrichloramine, add dodecyl dimethyl amine oxide after heating and stirring for ten minutes, add econazole nitrate after complete dissolution, keep stirring and dissolving under heating at 80 ℃, Stop heating after econazole nitrate is fully dissolved;

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

Table 12 Results of different process tests

Example 10 Clinical trial of the therapeutic effect of pet dogs and cats on parasitic skin diseases

1. Experimental animals

A total of 40 natural cases of parasitic skin diseases of dogs and cats in Xinxing Remigao pet dog farm in Yunfu City, Guangdong Province were selected. There are 20 dogs and 20 cats.

2. Experimental method

(1) Clinical examination: carry out clinical general examination, including routine indicators such as body temperature, respiration, heart rate, etc.; local examination of the degree of pruritus on the body surface, the degree of skin damage, the number of rashes or pustules, and the location and distribution of skin lesions.

(2) Inspection of ectoparasites: Take the skin of the affected part, observe under a microscope and count the number of ectoparasites in the local lesions. For flea infestation: count and count the number of fleas, distribution and quantity of flea feces; for tick bite dermatitis: count and count the number of ticks and skin lesions.

(3) Administration method

Wet the dog or cat's hair with water and apply the shampoo all over the body, avoiding the eyes, nose and mouth. Shampoo and massage, making sure the product is in contact with the skin and fur for 10 minutes. Rinse off with water and wear an Elizabethan ring to ensure dogs and cats don't lick themselves or lather while bathing. The experimental drug group used the shampoo of Example 3 twice a week, and the amount of the shampoo used each time was 1-2 mg/kg animal; the blank group was not using the shampoo as a control.

(4) Efficacy evaluation indicators:

Effective: The average reduction rate of the number of ectoparasites in the skin during and after the drug treatment period is ≥ In 90% of cases, there was no itching in the affected area, no rash, dandruff or self-biting injury of the experimental animals.

Ineffective: During and after the drug treatment, the average reduction rate of ectoparasites on the skin is less than 90%, the affected part is still itchy, rash, dander, etc., and the animal self-gnawing injury is obvious.

Monitoring of recurrence rate: The clinical symptoms of the skin and the number of skin parasites were monitored within 1 week after drug withdrawal in the cured dogs and cats.

3. Experimental results

(1) Efficacy evaluation results

Table 13 The results of the clinical trial of clinical parasitic skin diseases in pet dogs and cats

As can be seen from Table 13, the cure rate of the pet shampoo of the present invention to dogs suffering from parasitic skin disease reaches 100%, and the cure rate to cats suffering from parasitic skin disease reaches 90%.

(2) Monitoring results of recurrence rate

Observed within 1 week after drug withdrawal, in the experimental treatment group, 10 dogs were cured of parasitic skin disease and there was no recurrence case, and 9 cats were cured of parasitic skin disease and had 1 case of recurrent parasitic skin disease; It can be seen that after the shampoo of the present invention is applied, the parasites on the body surface of the pet can be effectively expelled, so that the pet is free from the trouble of parasites.

Example 10 Trial of the therapeutic effect of clinical fungal skin disease in pet dogs and cats

1. Experimental animals

A total of 40 cases of natural onset of dog and cat fungal skin disease in Xinxing Remigao Pet Dog Farm, Yunfu City, Guangdong Province were selected. Among them, there are 20 dogs and 20 cats.

2. Experimental method

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

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

(3) Administration method

Wet the dog or cat's hair with water and apply the shampoo all over the body, avoiding the eyes, nose and mouth. Shampoo and massage, making sure the product is in contact with the skin and fur for 10 minutes. Rinse off with water and wear an Elizabethan ring to ensure dogs and cats don't lick themselves or lather while bathing. The experimental drug group (the shampoo of Example 3) was used twice a week, and the amount of the shampoo used each time was 1-2 mg/kg of animals. The blank group used no shampoo as a control.

(4) Efficacy evaluation index

Cure: After taking the medicine, the isolation rate of pathogenic fungi on the skin is ≥80%, and the inflammatory secretions disappear significantly, the affected part has no peculiar smell, the rashes, dandruff, pustules, etc. disappear significantly, and the itching symptoms disappear significantly.

Effective: After the medication, the isolation rate of pathogenic fungi on the skin is ≥60%, and the inflammatory secretions are reduced, the affected area is basically free of peculiar smell, the rash, dandruff, pustules, etc. are reduced, and the itching symptoms are relieved.

Ineffective: After the medication, the isolation rate of pathogenic fungi on the skin is less than 60%, and the inflammatory secretions still exist, the affected part still has peculiar smell, the rash, dandruff, pustules, etc. have not been reduced, and the affected part still has obvious symptoms. Itching symptoms.

(5) Monitoring of recurrence rate: After stopping the treatment for cured dogs and cats 1 Skin clinical symptoms and skin microbiological examination within a week.

3. Test results

(1) Efficacy evaluation results

Table 14 Experimental results of clinical fungal skin diseases in pet dogs and cats

As can be seen from Table 14, the cure rate of the pet shampoo of the present invention to dogs and cats with fungal skin diseases is as high as 90%.

(2) Monitoring results of recurrence rate

Observation within 1 week after drug withdrawal showed that in the experimental treatment group, 9 dogs with fungal skin disease had no recurrence after being cured, and 1 case of recurrent fungal skin disease was found in 9 cats after being cured; After the shampoo of the invention is applied, the pet fungal skin disease can be effectively improved, and the recurrence rate is low.

Example 11 Experiment on the therapeutic effect of clinical bacterial skin disease in pet dogs and cats

1. Experimental animals

A total of 40 cases of naturally occurring bacterial skin diseases of dogs and cats in Xinxing Remigao Pet Dog Farm, Yunfu City, Guangdong Province were selected. Among them, there are 20 dogs and 20 cats.

2. Experimental method

(3) Administration method

Wet the dog or cat's hair with water and apply the shampoo all over the body, avoiding the eyes, nose and mouth. Shampoo and massage, making sure the product is in contact with the skin and fur for 10 minutes. Rinse off with water and wear an Elizabethan ring to ensure dogs and cats don't lick themselves or lather while bathing. The experimental drug group (the shampoo of Example 3) was used twice a week, and the amount of the shampoo used each time was 1-2 mg/kg of animals. The blank group used no shampoo as a control. .

(4) Efficacy evaluation index

Cure: After taking the medicine, the isolation and conversion rate of pathogenic bacteria on the skin is ≥80%, and the inflammatory secretions disappear significantly, the affected part has no peculiar smell, the rash, dandruff, pustules, etc. disappear significantly, and the itching symptoms disappear significantly.

Effective: After taking the medicine, the isolation rate of pathogenic bacteria on the skin is ≥60%, and the inflammatory secretions are reduced, the affected area is basically free of peculiar smell, the rash, dandruff, pustules, etc. are reduced, and the itching symptoms are relieved.

Ineffective: After the medication, the isolation rate of pathogenic bacteria on the skin is less than 60%, and the inflammatory secretions still exist, the affected area still has peculiar smell, the rash, dandruff, pustules, etc. have not been reduced, and the affected area still has obvious symptoms. Itching symptoms.

(5) Monitoring of recurrence rate: The clinical symptoms and skin microbiological examinations of the cured dogs and cats were conducted within 1 week after drug withdrawal.

3. Test results

(1) Efficacy evaluation results

Table 15 Experimental results of clinical treatment of bacterial skin diseases in pet dogs and cats

As can be seen from Table 15, the pet shampoo of the present invention has a cure rate of 90% for dogs with bacterial skin disease, and a cure rate of 100% for cats with bacterial skin disease.

(2) Monitoring results of recurrence rate

Observed within 1 week after drug withdrawal, in the experimental treatment group, 9 dogs with bacterial skin disease had no recurrence after being cured, and 10 cats had no recurrence of bacterial skin disease after being cured. It can be seen that, After the shampoo of the present invention is applied, the pet bacterial skin disease can be effectively improved, and the recurrence rate is low.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit the scope of protection of the present invention. For those of ordinary skill in the art, on the basis of the above descriptions and ideas, other Variations or variations in different forms need not and cannot be exhaustive of all implementations here. Any modifications, equivalent replacements and improvements made within the spirit and principle of the present invention shall be included within the protection scope of the claims of the present invention.

Claims

A pet shampoo with the functions of treating external parasitic skin diseases and antibacterial is characterized in that, the total mass part is calculated by 100 parts, and comprises the following components: 0.1-2 parts of fipronil, 1-5 parts of antifungal agent , 1-5 parts of antibacterial agent, 5-15 parts of alkyl glycoside, 20-30 parts of cocamidopropyl betaine, 2-10 parts of dodecyl dimethyl amine oxide, 1-10 parts of thickener , 0.1 to 2 parts of chelating agent, 0.1 to 5 parts of conditioner, 0.01 to 1 part of preservative, and deionized water to make up.
The pet shampoo according to claim 1, characterized in that, the total mass part is calculated by 100 parts, and comprises the following components: 0.2-2 parts of fipronil, 1-3 parts of antifungal agent, and 1-3 parts of antibacterial agent parts, 6-15 parts of alkyl glycosides, 20-30 parts of cocamidopropyl betaine, 6-10 parts of dodecyl dimethyl amine oxide, 1-5 parts of thickener, 0.1-1 part of chelating agent , 0.1 to 1 part of conditioner, 0.01 to 0.125 part of preservative, and deionized water to make up.
The pet shampoo according to claim 1, wherein the mass ratio of the alkyl glycoside, cocamidopropyl betaine and dodecyl dimethyl amine oxide is 10-15:20-30:10.
The pet shampoo according to claim 1, wherein the thickener is cetearyl glucoside, acrylate copolymer emulsion, thickener-SCC68, fatty polyethylene glycol ether, methyl glucose One or more of dioleates.
The pet shampoo according to claim 1, wherein the antifungal agent is one or more of ketoconazole, econazole nitrate, miconazole nitrate, clotrimazole and fluconazole.
The pet shampoo according to claim 1, wherein the antibacterial agent is benzalkonium chloride, benzalkonium bromide, chlorhexidine acetate, chlorhexidine gluconate, triclosan, polyhexamethylene biguanide one or more of them.
The pet shampoo according to claim 1, wherein the chelating agent is one or more of EDTA and disodium EDTA.
The pet shampoo according to claim 1, wherein the conditioning agent is cetrimonium chloride, one or more of water-soluble lanolin, aminosilicone oil, and aminosilicone oil microemulsion.
The pet shampoo according to claim 1, wherein the preservative is one or more of potassium sorbate, sodium dehydroacetate, sodium benzoate, and Kassone.
the preparation method of the described pet shampoo of any one of claim 1～9, is characterized in that, comprises the following steps:

(1) First, heat deionized water that accounts for 35% of the total volume of the shampoo to 60-80 °C, then add alkyl glycosides, cocamidopropyl betaine and dodecyl dimethyl amine oxide into deionized water and stir Dissolve, add fipronil after complete dissolution, add antifungal agent after fipronil is completely dissolved, keep stirring and dissolve under heating at 60-80 °C, add conditioning agent after antifungal agent is fully dissolved, wait for conditioning agent Stop heating after complete dissolution;

(2) After the heating is stopped in step (1), add a chelating agent and stir to dissolve. When cooled to 40-50 °C, add an antibacterial agent to stir and dissolve. After the antibacterial agent is completely dissolved, add a thickener to stir and dissolve. After completely dissolving, add preservatives and the balance of deionized water, and stir evenly.