Novel anthelmintic based on fipronil drops

Abstract

The invention belongs to the technical field of pet products, and particularly discloses a novel anthelmintic based on fipronil drops, which can effectively reduce the bacterial or fungal infection caused by parasites on the body surface or skin of pets by combining the antibacterial effects of fipronil, citronella extract and tripterygium wilfordii. The fipronil can quickly kill parasites, the citronella extract can further reduce breeding and contact of the parasites through a repelling effect, so that the overall effect of the medicine is accelerated, the citronella extract further reduces the secondary infection risk caused by the parasites by inhibiting growth of bacteria, and the tripterine further reduces the secondary infection risk caused by the parasites by inhibiting pathogenic microorganisms of skin. Through the synergistic effect of multiple components, the development of drug resistance of parasites to a single component can be reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of pet supplies, and particularly relates to a novel anthelmintic drug based on fipronil drops. Background Art

[0002] Fipronil, also known as flufenoxuron, is a phenylpyrazole insecticide that has been widely used in the agricultural and veterinary fields since its discovery. Its mechanism of action is to bind to the γ-aminobutyric acid (GABA) receptor on the central nerve cell membrane of insects, close the chloride ion channels of nerve cells, thereby interfering with the normal function of the central nervous system and causing the death of insects.

[0003] In the pet market, fipronil drops are commonly used drugs for killing ectoparasites on dogs and cats. However, the existing fipronil drops have an excessive amount of fipronil. At the same time, the single use of fipronil may lead to drug resistance problems, and it lacks antibacterial and anti-infection effects.

[0004] In view of this, the present application is proposed. Summary of the Invention

[0005] The present invention provides a novel anthelmintic drug based on fipronil drops, and the anthelmintic drug has excellent anthelmintic and antibacterial effects.

[0006] The present invention solves its technical problems by adopting the following technical solutions: A novel anthelmintic drug based on fipronil drops, comprising the following components in weight percentages: 1-6% fipronil, 3-12% citronella extract, 1-5% wilfordine, 0.2-1% menthol, 0.5-2% surfactant, 0.5-2% Tween 80, 1-3% polyvinylpyrrolidone, 2-5% penetration enhancer, 20-30% N-methylpyrrolidone, and the balance being solvent.

[0007] Fipronil: It mainly exerts its anthelmintic effect by interfering with the nerve conduction of insects. Fipronil can inhibit the acetylcholinesterase of insects, thereby causing disorder of nerve signal conduction and ultimately leading to the death of insects. It is a broad-spectrum insecticide and has a killing effect on various agricultural, livestock, sanitary pests and mites.

[0008] Citronella extract: It has significant antibacterial, anti-inflammatory, anthelmintic and mosquito-repellent effects, has a repellent effect on various mosquitoes, is a natural mosquito repellent, can effectively inhibit the growth of various bacteria and fungi, effectively prevent and treat skin infection and other problems, and achieves the anthelmintic effect by disturbing the olfactory system of insects and making them lose their attraction to the host.

[0009] Tripterygium alkaloid: It mainly inhibits the growth and reproduction of insects. Tripterygium alkaloid is toxic and can interfere with the nervous and endocrine systems of insects, inhibiting their normal physiological functions. At the same time, tripterygium alkaloid has strong antibacterial and antifungal effects, can effectively inhibit the growth of bacteria and fungi, and has advantages especially in the treatment of secondary infections caused by parasites.

[0010] By combining the antibacterial effects of fipronil, citronella extract, and tripterygium alkaloid, it can effectively reduce the bacterial or fungal infections on the surface or skin of pets caused by parasites. Fipronil can quickly kill parasites, and citronella extract can further reduce the breeding and contact of parasites through repellent effects, thus accelerating the overall effect of the drug. Citronella extract inhibits the growth of bacteria, while tripterygium alkaloid inhibits dermatopathic microorganisms, further reducing the risk of secondary infections caused by parasites. Through the synergistic effect of multiple components, the development of drug resistance of parasites to a single component can be reduced.

[0011] As a preferred embodiment of the present invention, it includes the following components in weight percentages: 2 - 5% fipronil, 7 - 8% citronella extract, 2 - 4% tripterygium alkaloid, 0.2 - 1% menthol, 0.5 - 2% surfactant, 0.5 - 2% Tween 80, 1 - 3% polyvinylpyrrolidone, 2 - 5% penetration enhancer, 20 - 30% N-methylpyrrolidone, and the balance is solvent. Especially when the dosages of each raw material are controlled within this range, the described anthelmintic drug has better anthelmintic and antibacterial effects.

[0012] As a preferred embodiment of the present invention, the solvent includes at least one of N-methylpyrrolidone, propylene glycol, and ethanol.

[0013] As a preferred embodiment of the present invention, the penetration enhancer includes diethylene glycol monoethyl ether.

[0014] As a preferred embodiment of the present invention, the surfactant includes at least one of sodium dodecylbenzenesulfonate and sodium dodecyl sulfate.

[0015] As a preferred embodiment of the present invention, the preparation method of the citronella extract is as follows: (1) Crush citronella to obtain citronella powder; (2) Add the citronella powder to the mixed solution and perform ultrasonic-assisted extraction to obtain an extract; (3) Ultrafilter the enzymatic hydrolysate first with an ultrafiltration membrane with a molecular weight cut-off of 1000 Da, then ultrafilter it with an ultrafiltration membrane with a molecular weight cut-off of 3000 Da, and dry it to obtain citronella extract.

[0016] As a preferred embodiment of the present invention, the particle size of the citronella powder is 50 - 400 mesh.

[0017] As a preferred embodiment of the present invention, the mixed solution comprises glycerol, trehalose, betaine, propylene glycol and water, and the mass ratio of glycerol, trehalose, betaine, propylene glycol to water is (2~10):(2~10):(1~5):(20~40):(30~70).

[0018] As a preferred embodiment of the present invention, the mass ratio of the citronella powder to the mixed solution is 1:(5~20).

[0019] As a preferred embodiment of the present invention, the temperature of the ultrasonic-assisted extraction is 48~55°C, the time is 2~6 h, and the ultrasonic power is 300~600 W.

[0020] Advantages of the present invention: By combining the antibacterial effects of fipronil, citronella extract and wilfordine, the present invention can effectively reduce the bacterial or fungal infections on the pet's body surface or skin caused by parasites. Fipronil can quickly kill parasites, and the citronella extract can further reduce the breeding and contact of parasites through its repellent effect, thus accelerating the overall effect of the drug. The citronella extract inhibits the growth of bacteria, and wilfordine inhibits dermatopathic microorganisms, further reducing the risk of secondary infections caused by parasites. Through the synergistic effect of multiple components, the development of drug resistance of parasites to a single component can be reduced. Detailed implementation manners

[0021] To make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Apparently, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0022] In the present invention, among the technically characterized described in an open-ended manner, there are included closed technical solutions composed of the listed features, as well as open technical solutions including the listed features.

[0023] In the present invention, regarding the numerical range, unless otherwise specified, the above numerical range is considered continuous and includes the minimum and maximum values of this range, as well as each value between such minimum and maximum values. Further, when the range refers to an integer, it includes each integer between the minimum and maximum values of this range. In addition, when providing multiple ranges to describe features or characteristics, these ranges can be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all sub-ranges subsumed therein.

[0024] In the present invention, there is no particular limitation on the specific dispersion and stirring treatment methods.

[0025] The reagents or instruments used in the present invention without indicating the manufacturer are all conventional products that can be obtained commercially. The raw materials used in the comparative examples and the raw materials used in the parallel experiments of the embodiments are the same commercially available products unless otherwise specified.

[0026] Example 1 A novel anthelmintic drug based on fepronil drops comprises the following components in weight percentage: 4% fepronil, 8% citronella extract, 2% tripterygium wilfordii alkaloids, 0.6% menthol, 1% sodium dodecylbenzene sulfonate, 1.2% Tween 80, 2% polyvinyl pyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance anhydrous ethanol.

[0027] The preparation method of the citronella extract is as follows: (1) Grinding the lemongrass into 200 meshes to obtain lemongrass powder; (2) adding citronella powder to the mixed solution, performing ultrasonic-assisted extraction at 50° C. for 4 h at 500 W to obtain an extract; the mixed solution comprises glycerol, trehalose, betaine, propylene glycol and water in a mass ratio of 5:8:4:30:53, and the mass ratio of the citronella powder to the mixed solution is 1:10; (3) The enzymatic hydrolyzate is first ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 1000Da, and then ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 3000Da, and dried to obtain a citronella extract.

[0028] The preparation method of the novel anthelmintic drug based on fepronil drops comprises the following steps: N-methylpyrrolidone, anhydrous ethanol, fepronil, citronella extract, triptolide, menthol, sodium dodecylbenzenesulfonate, Tween 80, polyvinylpyrrolidone and diethylene glycol monoethyl ether are uniformly mixed to obtain the novel anthelmintic drug based on fepronil drops.

[0029] Example 2 A novel anthelmintic drug based on fepronil drops comprises the following components in percentage by weight: 2% fepronil, 8% citronella extract, 4% tripterygium wilfordii alkaloids, 0.6% menthol, 1% sodium dodecylbenzene sulfonate, 1.2% Tween 80, 2% polyvinyl pyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance anhydrous ethanol.

[0030] The preparation method of the citronella extract is as follows: (1) Grinding the lemongrass into 200 meshes to obtain lemongrass powder; (2) adding citronella powder to the mixed solution, performing ultrasonic-assisted extraction at 50° C. for 4 h at 500 W to obtain an extract; the mixed solution comprises glycerol, trehalose, betaine, propylene glycol and water in a mass ratio of 5:8:4:30:53, and the mass ratio of the citronella powder to the mixed solution is 1:10; (3) Ultrafilter the enzymatic hydrolysate first with an ultrafiltration membrane with a molecular weight cut-off of 1000 Da, then with an ultrafiltration membrane with a molecular weight cut-off of 3000 Da, and dry to obtain citronella extract.

[0031] The preparation method of the novel insect repellent drug based on the fipronil drops includes the following steps: Mix N-methylpyrrolidone, absolute ethanol, fipronil, citronella extract, triptolide, menthol, sodium dodecylbenzenesulfonate, Tween 80, polyvinylpyrrolidone, and diethylene glycol monoethyl ether evenly to obtain the novel insect repellent drug based on the fipronil drops.

[0032] Example 3 A novel insect repellent drug based on the fipronil drops includes the following components by weight percentage: 1% fipronil, 12% citronella extract, 1% triptolide, 0.6% menthol, 1% sodium dodecylbenzenesulfonate, 1.2% Tween 80, 2% polyvinylpyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance is absolute ethanol.

[0033] The preparation method of the citronella extract is as follows: (1) Crush citronella to 200 meshes to obtain citronella powder; (2) Add the citronella powder to the mixed solution, and carry out ultrasonic-assisted extraction at 50 °C for 4 h with 500 W to obtain the extract; the mixed solution includes glycerol, trehalose, betaine, propylene glycol, and water with a mass ratio of 5:8:4:30:53, and the mass ratio of the citronella powder to the mixed solution is 1:10; (3) Ultrafilter the enzymatic hydrolysate first with an ultrafiltration membrane with a molecular weight cut-off of 1000 Da, then with an ultrafiltration membrane with a molecular weight cut-off of 3000 Da, and dry to obtain citronella extract.

[0034] The preparation method of the novel insect repellent drug based on the fipronil drops includes the following steps: Mix N-methylpyrrolidone, absolute ethanol, fipronil, citronella extract, triptolide, menthol, sodium dodecylbenzenesulfonate, Tween 80, polyvinylpyrrolidone, and diethylene glycol monoethyl ether evenly to obtain the novel insect repellent drug based on the fipronil drops.

[0035] Example 4 A novel insect repellent drug based on the fipronil drops includes the following components by weight percentage: 6% fipronil, 3% citronella extract, 5% triptolide, 0.6% menthol, 1% sodium dodecylbenzenesulfonate, 1.2% Tween 80, 2% polyvinylpyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance is absolute ethanol.

[0036] The preparation method of the citronella extract is as follows: (1) Grinding the lemongrass into 200 meshes to obtain lemongrass powder; (2) adding citronella powder to the mixed solution, performing ultrasonic-assisted extraction at 50° C. for 4 h at 500 W to obtain an extract; the mixed solution comprises glycerol, trehalose, betaine, propylene glycol and water in a mass ratio of 5:8:4:30:53, and the mass ratio of the citronella powder to the mixed solution is 1:10; (3) The enzymatic hydrolyzate is first ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 1000Da, and then ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 3000Da, and dried to obtain a citronella extract.

[0037] The preparation method of the novel anthelmintic drug based on fepronil drops comprises the following steps: N-methylpyrrolidone, anhydrous ethanol, fepronil, citronella extract, triptolide, menthol, sodium dodecylbenzenesulfonate, Tween 80, polyvinylpyrrolidone and diethylene glycol monoethyl ether are uniformly mixed to obtain the novel anthelmintic drug based on fepronil drops.

[0038] Comparative Example 1

[0039] The difference between Comparative Example 1 and Example 1 is that the amounts of fenpronil, citronella extract, and triptolide (the total amounts of fenpronil, citronella extract, and triptolide are the same) in Comparative Example 1 are not within the scope of the present invention, and the others are the same.

[0040] A novel anthelmintic drug based on fepronil drops comprises the following components in weight percentage: 0.5% fepronil, 13% citronella extract, 0.5% tripterygium wilfordii alkaloids, 0.6% menthol, 1% sodium dodecylbenzene sulfonate, 1.2% Tween 80, 2% polyvinyl pyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance anhydrous ethanol.

[0041] Comparative Example 2

[0042] The difference between Comparative Example 2 and Example 1 is that the amounts of fenpronil, citronella extract, and triptolide (the total amounts of fenpronil, citronella extract, and triptolide are the same) in Comparative Example 2 are not within the scope of the present invention, and the others are the same.

[0043] A novel anthelmintic drug based on fepronil drops comprises the following components in percentage by weight: 12.5% fepronil, 1% citronella extract, 0.5% tripterygium wilfordii, 0.6% menthol, 1% sodium dodecylbenzene sulfonate, 1.2% Tween 80, 2% polyvinyl pyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance anhydrous ethanol.

[0044] Comparative Example 3

[0045] The difference between Comparative Example 3 and Example 1 is that Comparative Example 3 does not contain pyriproxyfen (the total amount of pyriproxyfen, citronella extract, and triptolide is the same), and the others are the same.

[0046] A novel anthelmintic drug comprises the following components in percentage by weight: 10% citronella extract, 4% triptolide, 0.6% menthol, 1% sodium dodecylbenzenesulfonate, 1.2% Tween 80, 2% polyvinylpyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance anhydrous ethanol.

[0047] Comparative Example 4

[0048] The difference between Comparative Example 4 and Example 1 is that Comparative Example 4 does not contain citronella extract (the total amount of pyriproxyfen, citronella extract, and triptolide is the same), and the others are the same.

[0049] A novel anthelmintic drug based on pyriproxyfen drops comprises the following components in percentage by weight: 8% pyriproxyfen, 6% triptolide, 0.6% menthol, 1% sodium dodecylbenzenesulfonate, 1.2% Tween 80, 2% polyvinylpyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance anhydrous ethanol.

[0050] Comparative Example 5

[0051] The difference between Comparative Example 5 and Example 1 is that Comparative Example 5 does not contain triptolide (the total amount of pyriproxyfen, citronella extract, and triptolide is the same), and the others are the same.

[0052] A novel anthelmintic drug based on pyriproxyfen drops comprises the following components in percentage by weight: 5% pyriproxyfen, 9% citronella extract, 0.6% menthol, 1% sodium dodecylbenzenesulfonate, 1.2% Tween 80, 2% polyvinylpyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance anhydrous ethanol.

[0053] Comparative Example 6

[0054] The difference between Comparative Example 6 and Example 1 is that Comparative Example 6 uses an equal amount of pyrethrins to replace triptolide, and the others are the same.

[0055] A novel anthelmintic drug based on pyriproxyfen drops comprises the following components in percentage by weight: 4% pyriproxyfen, 8% citronella extract, 2% pyrethrins, 0.6% menthol, 1% sodium dodecylbenzenesulfonate, 1.2% Tween 80, 2% polyvinylpyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance anhydrous ethanol.

[0056] Comparative Example 7

[0057] The difference between Comparative Example 7 and Example 1 is that Comparative Example 7 uses an equal amount of chamomile extract to replace the citronella extract, and the other contents are the same.

[0058] A novel anthelmintic drug based on fepronil drops comprises the following components in percentage by weight: 4% fepronil, 8% chamomile extract, 2% tripterygium wilfordii alkaloids, 0.6% menthol, 1% sodium dodecylbenzene sulfonate, 1.2% Tween 80, 2% polyvinyl pyrrolidone, 3% diethylene glycol monoethyl ether, 25% N-methylpyrrolidone, and the balance anhydrous ethanol.

[0059] The preparation method of the chamomile extract is: (1) Grinding chamomile into 200 meshes to obtain chamomile powder; (2) adding chamomile powder to the mixed solution, performing ultrasonic-assisted extraction at 50°C for 4 h at 500 W to obtain an extract; the mixed solution comprises glycerol, trehalose, betaine, propylene glycol and water in a mass ratio of 5:8:4:30:53, and the mass ratio of chamomile to the mixed solution is 1:10; (3) The enzymatic hydrolyzate is first ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 1000Da, and then ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 3000Da, and dried to obtain a chamomile extract.

[0060] Comparative Example 8

[0061] The difference between Comparative Example 8 and Example 1 is that the preparation method of the citronella extract in Comparative Example 8 is different from that in Example 1, and the others are the same.

[0062] The preparation method of the citronella extract is as follows: (1) Grinding the lemongrass into 200 meshes to obtain lemongrass powder; (2) adding citronella powder to water, performing ultrasonic-assisted extraction at 50° C. for 4 h at 500 W to obtain an extract, wherein the mass ratio of citronella powder to water is 1:10; (3) The enzymatic hydrolyzate is first ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 1000Da, and then ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 3000Da, and dried to obtain a citronella extract.

[0063] Comparative Example 9

[0064] The difference between Comparative Example 9 and Example 1 is that the preparation method of the citronella extract in Comparative Example 9 is different from that in Example 1, and the others are the same.

[0065] The preparation method of the citronella extract is as follows: (1) Grinding the lemongrass into 200 meshes to obtain lemongrass powder; (2) Add citronella powder to the mixed solution, and perform ultrasonic-assisted extraction at 50 °C for 4 h at 500 W to obtain an extract; the mixed solution includes glycerol, trehalose, betaine, propylene glycol and water with a mass ratio of 5:8:4:30:53, and the mass ratio of the citronella powder to the mixed solution is 1:10; (3) Ultrafilter the enzymolysis solution first with an ultrafiltration membrane with a molecular weight cut-off of 5000 Da, and then ultrafilter it with an ultrafiltration membrane with a molecular weight cut-off of 10,000 Da, and dry it to obtain a citronella extract.

[0066] Test Example

[0067] 1. Detect the acaricidal rate according to NY / T 1151.2-2006.

[0068] 2. Refer to Appendix C of GB 15979-2002 Hygiene Standards for Disposable Sanitary Products for testing, and the test strain is Candida albicans.

[0069] Table 1

[0070] It can be seen from Table 1 that the insect repellent drug described in the present invention has excellent insect repellent and antibacterial effects.

[0071] Finally, it should be noted that the above embodiments are used to illustrate the technical solutions of the present invention rather than to limit the protection scope of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A novel anthelmintic drug based on pyriproxyfen drops, characterized in that, The invention comprises the following components in weight percentage: 1-6% of fepronil, 3-12% of citronella extract, 1-5% of tripterygium wilfordii alkaloids, 0.2-1% of menthol, 0.5-2% of surfactant, 0.5-2% of Tween 80, 1-3% of polyvinyl pyrrolidone, 2-5% of penetration enhancer, 20-30% of N-methyl pyrrolidone and the balance of solvent.

2. The novel anthelmintic drug based on the fipronil drops according to claim 1, characterized in that, The invention comprises the following components in weight percentage: 2-5% of fepronil, 7-8% of citronella extract, 2-4% of tripterygium wilfordii alkaloids, 0.2-1% of menthol, 0.5-2% of surfactant, 0.5-2% of Tween 80, 1-3% of polyvinyl pyrrolidone, 2-5% of penetration enhancer, 20-30% of N-methylpyrrolidone and the balance of solvent.

3. The novel anthelmintic drug based on pyriproxyfen drops according to claim 1, characterized in that, The solvent includes at least one of N-methylpyrrolidone, propylene glycol and ethanol.

4. The novel insect repellent drug based on the fipronil drops according to claim 1, characterized in that, The penetration enhancer includes diethylene glycol monoethyl ether.

5. The novel insect repellent drug based on fipronil drops according to claim 1, characterized in that, The surfactant comprises at least one of sodium dodecylbenzene sulfonate and sodium dodecyl sulfate.

6. The novel anthelmintic drug based on the fipronil drops according to claim 1, characterized in that, The preparation method of the citronella extract is as follows: (1) crushing the lemongrass to obtain lemongrass powder; (2) adding citronella powder to the mixed solution, performing ultrasound-assisted extraction, and obtaining an extract; (3) The enzymatic hydrolyzate is first ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 1000Da, and then ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 3000Da, and dried to obtain a citronella extract.

7. The novel insect repellent drug based on fipronil drops according to claim 6, characterized in that, The particle size of the citronella powder is 50-400 meshes.

8. The novel anthelmintic drug based on the fipronil drops according to claim 6, characterized in that, The mixed liquid includes glycerol, trehalose, betaine, propylene glycol and water, and the mass ratio of the glycerol, trehalose, betaine, propylene glycol and water is (2-10): (2-10): (1-5): (20-40): (30-70).

9. The novel anthelmintic drug based on pyriproxyfen drops according to claim 6, characterized in that, The mass ratio of the citronella powder to the mixed liquid is 1:(5-20).

10. The novel anthelmintic drug based on the fipronil drops according to claim 6, characterized in that, The temperature of the ultrasonic-assisted extraction is 48-55° C., the time is 2-6 hours, and the ultrasonic power is 300-600W.

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