Animal parasite control agent and preparation method thereof

Abstract

The invention provides an external parasite prevention and control agent for animals. The external parasite prevention and control agent comprises the following components in percentage by mass: 6-12% of fipronil; 1 to 5% of moxidectin; 1-3% of pyriproxyfen; 1-3% of a crystallization inhibitor; 0.3%-0.6% of an antioxidant; 3-5% of a main solvent; the total percentage is 100%. The fipronil is taken as a main effective component, and moxidectin and pyriproxyfen are cooperatively matched, so that the fipronil-containing insecticidal composition has a good insecticidal effect, and the problems that an existing insecticide is poor in insecticidal effect and cannot thoroughly kill ticks, mites and the like are solved; particularly, the animal external parasite control agent comprises 10% of fipronil, 1% of moxidectin, 1.8% of pyriproxyfen, 2% of propylene glycol, 0.1% of BHT, 0.2% of BHA, 3% of absolute ethyl alcohol, 2% of dimethyl sulfoxide and a proper amount of diethylene glycol monoethyl ether, and the insecticidal effect is particularly good.

Description

Technical Field

[0001] The present invention relates to the technical field of parasite medicines, in particular to an external parasite control agent for animals and a preparation method thereof. Background Art

[0002] The pet market is booming, with many families keeping cats, dogs, and other pets. However, these pets are extremely susceptible to parasites and infections, such as fleas, mites, ticks, and lice. Parasites not only cause anxiety and illness in pets, but also serve as intermediate hosts for pathogens, potentially causing a variety of zoonotic diseases in humans through pathogen infection and transmission. Numerous insecticides exist in the field for treating parasites, varying in their effectiveness against specific parasites and their cost. For example, fipronil, also known as fipronil, is a pyrazole compound discovered in 1987 by researchers at the French company Rhone-Poulenc. It has insecticidal, acaricidal, nematicidal, and arthropodicidal activity. This drug is primarily available for pets in two dosage forms: drops and sprays. After application, it is stored in the animal's sebaceous glands and diffuses through the oil on the skin surface to exert a systemic effect. The drug does not enter the body or blood circulation of cats and dogs, and does not harm their liver and kidney function. This product is convenient to use, but it is expensive, slow to take effect, and has little effect on insect eggs, with a tendency to relapse within a few days of use. Furthermore, the market has reported that existing drugs, such as Frontline, generally do not fully repel insects, especially ticks and mites. Therefore, it is necessary to design an external parasite control agent for animals that is effective against adults, larvae, and eggs, has excellent insect removal efficacy, is gentle on the skin, and can repel ants and insects. Summary of the Invention

[0003] The embodiments described below are only some of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0004] The invention provides an external parasite control agent for animals, which comprises the following components: fipronil, moxidectin, pyriproxyfen, a crystallization inhibitor, an antioxidant, a main solvent and a co-solvent.

[0005] The mass percentages of the components are as follows: fipronil 6-12%, which may be, but not limited to, 6%, 7%, 8%, 10%, or 12%; moxidectin 1-5%, which may be, but not limited to, 1%, 2%, 3%, 4%, or 5%; pyriproxyfen 1-3%, which may be, but not limited to, 1%, 2%, 2.5%, or 3%; crystallization inhibitor 1-3%, which may be, but not limited to, 1%, 2%, or 3%; antioxidant 0.3-0.6%, which may be, but not limited to, 0.3%, 0.4%, 0.5%, or 0.6%; main solvent 3-5%, which may be, but not limited to, 3%, 4%, or 5%; and the co-solvent is made up to 100%.

[0006] The antioxidants are BHA and BHT, wherein the mass ratio of BHA to BHT is 1:1, the crystallization inhibitor is propylene glycol, and the main solvent includes anhydrous ethanol and dimethyl sulfoxide.

[0007] Fipronil has a strong lipophilicity and can diffuse into the sebaceous glands of the hair follicles on the body surface for storage, thus having a long residual effect. Fipronil mainly blocks the nerve membrane Cl controlled by γ-aminobutyric acid receptors. - channel, induced Cl - The chlorpyrifos (Fipronil) has the advantages of broad spectrum and high efficacy, lacks cross-resistance with existing insecticides, and is effective against pests that are resistant or sensitive to organophosphorus, organochlorine, carbamate, pyrethroid, and other insecticides. However, it has the disadvantage of slow onset of action, which does not meet user needs in terms of speed of effect.

[0008] Described moxidectin is a kind of fermentation semi-synthetic macrolide antiparasitic drug, has efficient expelling and killing effect to nematodes and arthropods.The difference with other macrolide antiparasitic drugs such as ivermectin and avermectin (Avermectin, AVM) is that it is a single component, has higher anthelmintic activity and long-lasting, safe and other characteristics, especially to nematodes (adults and larvae) and arthropods, just has good antiparasitic activity at extremely low dosage.As a new generation of anthelmintic, moxidectin can kill nematodes and body surface parasites efficiently, and at the same time, has good safety to animals.It can be used in conjunction with fipronil and complement described fipronil, increase the expelling and killing effect to ticks and mites, speed up the insecticide speed, and insecticide efficiency is high and effective.

[0009] Pyriproxyfen can inhibit the physiological development of insects, such as by causing them to molt, inhibiting new cuticle formation, and inhibiting feeding. This hinders and interferes with the normal development of insects, preventing unhatched or metamorphosed larvae from emerging into adults and causing their death. The insect growth agent, when used in combination with pyriproxyfen and moxidectin, can further enhance the insecticidal effect on adults, larvae, and eggs, further improving the insecticidal efficacy.

[0010] The antioxidants are BHA and BHT, which can protect the fipronil, moxidectin and pyriproxyfen from being oxidized when they penetrate into the insect lipid layer, thereby maintaining the efficacy.

[0011] The main solvent is selected from anhydrous ethanol and dimethyl sulfoxide. The dimethyl sulfoxide is miscible with water, alcohol, ether, ester, ketone, halogenated hydrocarbon and aromatic hydrocarbon, has low volatility, good thermal stability and chemical stability, and has a large solubility for pyriproxyfen, moxidectin, etc. The anhydrous ethanol is easily soluble in alcohol, ether, ketone and ester, and has the inherent characteristics of being cheap, non-toxic, biodegradable and environmentally friendly. It is an ideal "green solvent" and has a large solubility for pyriproxyfen. The co-solvent is diethylene glycol monoethyl ether. The combination of the main solvent and the co-solvent has a good dissolving effect on the components in the animal external parasite control agent, thereby providing a good and stable system environment. In addition, the combination of the main solvent and the co-solvent has a fresh fragrance, which can cover and hide the unpleasant smell of the drug and increase the experience.

[0012] The crystallization inhibitor is propylene glycol, which has a wide solubility range and excellent compatibility, stability, and dispersibility, etc. It can effectively inhibit crystallization and prolong the residence time of the drug on the animal skin, thereby better exerting the repellent effect.

[0013] The present invention also provides a method for preparing the above-mentioned external parasite control agent for animals, comprising the following steps: Step 1. Provide the following components by weight: 6-12% fepronil; 1-5% moxidectin; 1-3% pyriproxyfen; 1-3% crystallization inhibitor; 0.3-0.6% antioxidant; 3-5% main solvent; and an appropriate amount of co-solvent. Step 2. Partially dissolve the fepronil, moxidectin, and pyriproxyfen in the main solvent. Step 3. Dissolve the antioxidant in an appropriate amount of co-solvent. Step 4. Mix the partially dissolved fepronil, moxidectin, pyriproxyfen, antioxidant, and crystallization inhibitor and stir thoroughly. Step 5. Add the co-solvent to 100%, stir thoroughly, and filter to obtain the topical parasite control agent for animals.

[0014] The external parasite control agent for animals can be a spray or a drop, which is used for expelling and killing parasites on the surface of animals, can effectively kill adults, larvae and eggs of parasites, and can effectively expel parasites and prevent parasite infections. It has good expelling effect and efficiency, a long lasting effect and a pleasant smell.

[0015] The following are specific embodiments: Example

[0016] The formula and preparation method of the external parasite control agent for animals provided by the present invention are as follows (1L): Step 1: Provide the following components by weight: 10% fepronil (i.e., 100 g); 1% moxidectin (i.e., 10 g); 1.8% pyriproxyfen (i.e., 18 g); 1% propylene glycol (i.e., 10 ml); 0.3% BHT (i.e., 3 g); 0.3% BHA (i.e., 3 g); 3% anhydrous ethanol (i.e., 30 ml); 1% dimethyl sulfoxide (i.e., 10 ml); and an appropriate amount of diethylene glycol monoethyl ether. Step 2: Partially dissolve the fepronil, moxidectin, and pyriproxyfen in 30 ml of anhydrous ethanol and 10 ml of dimethyl sulfoxide. Step 3: Take an appropriate amount of diethylene glycol monoethyl ether to completely dissolve all BHT and BHA, stir thoroughly, and form a colorless solution; Step 4: Mix the partially dissolved fipronil, moxidectin, and pyriproxyfen with the completely dissolved antioxidant and crystallization inhibitor and stir thoroughly until all solid materials are completely dissolved; Step 5: Add the diethylene glycol monoethyl ether to 1 L, stir thoroughly, and filter to obtain the external parasite control agent for animals. Example

[0017] The formula and preparation method of the external parasite control agent for animals provided by the present invention are as follows (1L): Step 1: Provide the following components by weight percentage: 6% (60g) of fepronil; 2% (20g) of moxidectin; 2% (20g) of pyriproxyfen; 3% (30ml) of propylene glycol; 0.2% (2g) of BHT; 0.2% (2g) of BHA; 2% (20ml) of anhydrous ethanol; 2.5% (25ml) of dimethyl sulfoxide; and an appropriate amount of diethylene glycol monoethyl ether. Step 2: Measure 20ml of anhydrous ethanol and 25ml of dimethyl sulfoxide to partially dissolve the fepronil, moxidectin, and pyriproxyfen. Step 3: Take an appropriate amount of diethylene glycol monoethyl ether to completely dissolve all of the BHT and BHA, and stir thoroughly to form a colorless solution. Step 4: Mix the partially dissolved fepronil, moxidectin, and pyriproxyfen with the completely dissolved antioxidant and crystallization inhibitor, and stir thoroughly until all solid materials are completely dissolved. Step 5: Add the diethylene glycol monoethyl ether to 1 L, stir thoroughly, and filter to obtain the external parasite control agent for animals. Example

[0018] The formula and preparation method of the external parasite control agent for animals provided by the present invention are as follows (1L): Step 1: Provide the following components by weight: 10% (i.e., 100g) of fepronil; 1% (i.e., 10g) of moxidectin; 1.8% (i.e., 18g) of pyriproxyfen; 2% (i.e., 20ml) of propylene glycol; 0.3% (i.e., 3g) of BHT; 0.3% (i.e., 3g) of BHA; 3% (i.e., 30ml) of anhydrous ethanol; 2% (i.e., 20ml) of dimethyl sulfoxide; and an appropriate amount of diethylene glycol monoethyl ether. Step 2: Measure 30ml of anhydrous ethanol and 20ml of dimethyl sulfoxide to partially dissolve the fepronil, moxidectin, and pyriproxyfen. Step 3: Take an appropriate amount of diethylene glycol monoethyl ether to completely dissolve all of the BHT and BHA, and stir thoroughly to form a colorless solution. Step 4: Mix the partially dissolved fepronil, moxidectin, and pyriproxyfen with the completely dissolved antioxidant and crystallization inhibitor, and stir thoroughly until all solid materials are completely dissolved. Step 5: Add the diethylene glycol monoethyl ether to 1 L, stir thoroughly, and filter to obtain the external parasite control agent for animals. Example

[0019] The formula and preparation method of the external parasite control agent for animals provided by the present invention are as follows (1L): Step 1: Provide the following components by weight percentage: 6% (60g) of fepronil; 3% (30g) of moxidectin; 2.5% (25g) of pyriproxyfen; 3% (30ml) of propylene glycol; 0.25% (2.5g) of BHT; 0.25% (2.5g) of BHA; 2% (20ml) of anhydrous ethanol; 3% (30ml) of dimethyl sulfoxide; and an appropriate amount of diethylene glycol monoethyl ether. Step 2: Measure 20ml of anhydrous ethanol and 30ml of dimethyl sulfoxide to partially dissolve the fepronil, moxidectin, and pyriproxyfen. Step 3: Take an appropriate amount of diethylene glycol monoethyl ether to completely dissolve all of the BHT and BHA, and stir thoroughly to form a colorless solution. Step 4: Mix the partially dissolved fepronil, moxidectin, and pyriproxyfen with the completely dissolved antioxidant and crystallization inhibitor, and stir thoroughly until all solid materials are completely dissolved. Step 5: Add the diethylene glycol monoethyl ether to 1 L, stir thoroughly, and filter to obtain the external parasite control agent for animals.

[0020] Efficacy test of the external parasite control agent for animals provided by the present invention Test method: Dog breeding farm selects clinical symptoms typical, 50 sick dogs with ectoparasites are diagnosed by veterinarian and microscopy, and are randomly divided into 10 groups, namely test group 1, test group 2, test group 3, test group 4, 5 in each group. Test group 1 gives the control agent of embodiment 1, gives 1ml by every 2.5kg body weight, drips between the dog's back shoulder and foot bones, uses medicine 1 time, and observes cure. Test group 2 gives the control agent of embodiment 2, gives 1ml by every 2.5kg body weight, drips between the dog's back shoulder and foot bones, uses medicine 1 time, and observes cure. Test group 3 gives the control agent of embodiment 3, gives 1ml by every 2.5kg body weight, drips between the dog's back shoulder and foot bones, uses medicine 1 time, and observes cure. Test group 4 gives the control agent of embodiment 4, gives 1ml by every 2.5kg body weight, drips between the dog's back shoulder and foot bones, uses medicine 1 time, and observes cure. The control group 5 was given single-prescription fepronil drops, 1 ml per 2.5 kg body weight, according to the standard administration method, and the medication was used once. The sick dogs in experimental group 1, experimental group 2, experimental group 3, experimental group 4 and control group 5 were observed and recorded once a week 3 days, 1 week, 2 weeks, and 3 weeks after medication for 20 weeks.

[0021] Before medication and on days 3, 7, 14, 21, 28, 42, 56, 84, 112, and 140 after medication, samples were collected from the affected areas of the sick dogs to collect information on mites, ticks, fleas, and lice.

[0022] Mite data points: scored on a scale of 0 to 3, with level 0 indicating no mite lesions, no live mites; level 1 indicating 10 mite lesions, no live mites; level 2 indicating 11-20 mite lesions, no live mites; and level 3 indicating more than 20 mite lesions, no live mites.

[0023] Tick ​​data points: scored on a scale of 0 to 3, with level 0 indicating no tick-induced local congestion or inflammation and no live ticks in the lesions; level 1 indicating five ticks causing local congestion or inflammation and live ticks in the lesions; level 2 indicating six to ten ticks causing local congestion or inflammation and live ticks in the lesions; and level 3 indicating more than ten ticks causing local congestion or inflammation and live ticks in the lesions.

[0024] Flea data points: scored on a scale of 0 to 3, with level 0 indicating no flea-induced lesions, hair loss, scabs, or live fleas on the dog; level 1 indicating 10 fleas-induced lesions, hair loss, scabs, or live fleas on the dog; level 2 indicating 11 to 20 fleas-induced lesions, hair loss, scabs, or live fleas on the dog; and level 3 indicating more than 20 fleas-induced lesions, hair loss, scabs, or live fleas on the dog.

[0025] Lice data score: scored on a scale of 0 to 3, with level 0 indicating no lice causing scabies or live lice; level 1 indicating 10 lice causing scabies or live lice; level 2 indicating 11 to 20 lice causing scabies or live lice; and level 3 indicating more than 20 lice causing scabies or live lice.

[0026] Table 1 Clinical efficacy scores of each group of control agents and single prescription Feiporoximate drops on canine parasites:

[0027] The data in the table are calculated strictly according to the rounding rule.

[0028] Analysis of the results: The single administration of the external parasite control agent for animals provided in Examples 1 and 3 can kill mites, ticks, fleas and lice on dogs within 1 month, and the therapeutic effect is maintained for at least 4 months without secondary infection, indicating that the control agent kills both adults and larvae while also killing eggs, fundamentally solving the pest problem. In particular, Example 1 has an efficient and rapid insecticidal effect and low theoretical toxicity, making it the optimal formulation. Although the other embodiments of the present invention do not have the therapeutic effect of the product of Example 3, they have better therapeutic effects than the single-prescription Feipoluoni drops on the market. Except for Example 4, all of them can kill parasites in the later stage and there is no secondary infection during the test period. Even Example 4, although not all eggs are killed and no secondary infection can be maintained for a long time, can also kill all live parasites and some eggs within a certain period of time, and has better insecticidal effects than the single-prescription Feipoluoni drops.

[0029] The above disclosures are merely some preferred embodiments of the present invention, which certainly cannot be used to limit the scope of the present invention. Therefore, equivalent changes made according to the scope of the patent application of the present invention are still within the scope covered by the present invention.

Claims

1. An external parasite control agent for animals, characterized in that: The mass percentages of the components of the animal parasite control agent are as follows: Fipronil 5-15%; Moxidectin 1-5% Pyriproxyfen 1~3%; Crystallization inhibitor 1~3%; Antioxidant 0.3~0.6%; Main solvent 3~5%; The co-solvent was made up to 100%.

2. The external parasite control agent for animals according to claim 1, wherein The mass percentages of the components of the animal parasite control agent are as follows: 10% of fipronil; 1% of moxidectin; 1.8% of pyriproxyfen; 2% of a crystallization inhibitor; 0.6% of an antioxidant; 4% of a main solvent; and the co-solvent is supplemented to 100%.

3. The external parasite control agent for animals according to claim 2, wherein The antioxidants are BHA and BHT, wherein the mass ratio of the BHA to the BHT is 1:

1.

4. The external parasite control agent for animals according to claim 2, wherein The crystallization inhibitor is propylene glycol.

5. The external parasite control agent for animals according to claim 2, wherein The main solvent includes anhydrous ethanol and dimethyl sulfoxide, wherein the mass percentages of anhydrous ethanol and dimethyl sulfoxide in the external parasite control agent for animals are 3% and 1% respectively.

6. A method for preparing an external parasite control agent for animals, for preparing the external parasite control agent for animals according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) Provide the following components by weight percentage: 6-12% of fepronil; 1-5% of moxidectin; 1-3% of pyriproxyfen; 1-3% of crystallization inhibitor; 0.3-0.6% of antioxidant; 3-5% of main solvent; and appropriate amount of co-solvent. (2) using a main solvent to partially dissolve the fipronil, the moxidectin, and the pyriproxyfen; (3) using an appropriate amount of co-solvent to dissolve the antioxidant; (4) Mixing and stirring the partially dissolved fipronil, moxidectin, pyriproxyfen, antioxidant and crystallization inhibitor thoroughly; (5) Add the co-solvent to 100%, stir thoroughly, and filter to obtain the external parasite control agent for animals.

7. The method for preparing the external parasite control agent for animals according to claim 6, wherein: The mass percentages of the components of the animal parasite control agent are as follows: 10% of fipronil; 1% of moxidectin; 1.8% of pyriproxyfen; 2% of a crystallization inhibitor; 0.6% of an antioxidant; 4% of a main solvent; and the co-solvent is supplemented to 100%.

8. The method for preparing the external parasite control agent for animals according to claim 7, wherein: The antioxidants are BHA and BHT, wherein the mass ratio of the BHA to the BHT is 1:

1.

9. The method for preparing the external parasite control agent for animals according to claim 8, wherein: The main solvent includes anhydrous ethanol and dimethyl sulfoxide, wherein the mass percentages of anhydrous ethanol and dimethyl sulfoxide in the external parasite control agent for animals are 3% and 1% respectively.

10. The method for preparing the external parasite control agent for animals according to claim 9, wherein: The specific steps include: (1) Provide the following components by weight percentage: 10% of fepronil; 1% of moxidectin; 1.8% of pyriproxyfen; 2% of propylene glycol; 0.3% of BHT; 0.3% of BHA; 3% of anhydrous ethanol; 1% of dimethyl sulfoxide; and an appropriate amount of diethylene glycol monoethyl ether; (2) Partially dissolve the fipronil, moxidectin, and pyriproxyfen in anhydrous ethanol and dimethyl sulfoxide, respectively, and stir thoroughly until partially dissolved; (3) Use an appropriate amount of diethylene glycol monoethyl ether to completely dissolve all BHT and BHA, stir thoroughly, and form a colorless solution; (4) Mixing and stirring the partially dissolved fipronil, moxidectin, pyriproxyfen, antioxidant and crystallization inhibitor thoroughly; (5) Add the diethylene glycol monoethyl ether to 100%, stir thoroughly, and filter to obtain the external parasite control agent for animals.

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