CN115671040A - External preparation for controlling animal parasitic infection - Google Patents
External preparation for controlling animal parasitic infection Download PDFInfo
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- CN115671040A CN115671040A CN202110824165.0A CN202110824165A CN115671040A CN 115671040 A CN115671040 A CN 115671040A CN 202110824165 A CN202110824165 A CN 202110824165A CN 115671040 A CN115671040 A CN 115671040A
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- external preparation
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- dipropylene glycol
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
The invention discloses an external preparation for controlling animal parasite infection, which is characterized by comprising isoxazoline, macrolide, acceptable liquid carrier vehicle and antioxidant. The composition has broad spectrum of insecticidal activity, no adverse reaction of external preparation to skin, and long-lasting stability.
Description
Technical Field
The invention belongs to the technical field of medicinal preparations, relates to an external preparation of an antibacterial medicament for livestock, and particularly relates to an external preparation for controlling animal parasitic infection.
Technical Field
Controlling parasitic infections in animal populations has been an important global task. Pathogenic organisms can be classified as endoparasites of the classes nematoda, cestoda and trematoda or phylum protozoa, or ectoparasites of the phylum arthropoda. The former includes infections of the stomach, intestinal tract, lymphatic system, tissue, liver, lung, heart and brain. The latter are related to ectoparasites including ticks, mites, lice, flies, and fleas, which are often used as vectors and intermediate hosts for the transmission of endoparasites to animal hosts.
Although many ectoparasiticides and endoparasiticides are in use, these have a number of problems, such as a limited spectrum of activity, the need for repeated treatments, and in many cases resistance to parasitics.
The isoxazoline compound is a broad-spectrum pesticide, has good insecticidal activity on pests of the orders of tick, flea, louse, hemiptera, diptera and the like, and has higher toxicity or equivalent toxicity to that of a common pesticide. Macrolide compounds are antibiotics fermented from new strains of gene recombination, have wide inhibition and killing effects on parasites in and out of animals, including fleas, scabies, ticks, hookworms, lice, nematodes, heartworms and the like, and have the advantages of good curative effect, low toxicity and the like.
The combination of the isoxazoline compound and the macrolide compound has obvious advantages in the aspect of insecticidal activity spectrum and has obvious inhibition effect on different parasites. The external preparation and the oral tablet basically keep consistent in drug effect, the external preparation is more convenient to use, quick in effect taking and obvious in targeting effect, and the combined external preparation of the isoxazoline and the macrolide has obvious inhibiting and killing effects on most of internal and external parasites, so that the isoxazoline and the macrolide are suitable for being prepared into external preparations for expelling the parasites.
However, the antioxidant butylated hydroxytoluene artificially synthesized in a certain proportion is added into the existing external preparation to ensure the stability of the external solvent. Butylated Hydroxytoluene (BHT) is a common lipid antioxidant used in external formulations to improve the stability of the dosage form. The cosmetic is used as antiseptic, and has small addition amount. The researches of a plurality of organizations such as the world health organization, the European Union Children protection organization, the British biological industry Association and the like show that butylated hydroxytoluene can be absorbed by skin, skin inflammation and allergy can be easily caused after long-term use or one-time excessive use, even the adverse effect can be generated on liver, spleen and lung, and meanwhile, butylated hydroxytoluene can be discolored and lose activity under the conditions of light, humidity, heat and the like, so that the antioxidant effect of the butylated hydroxytoluene is obviously reduced.
The components of the pharmaceutical preparation have higher irritation to the body and higher requirement on the stability of the medicament than those of the cosmetic, the dosage of the stabilizer needs to be increased, and the components of the external antibacterial pharmaceutical preparation are urgently required to be improved in order to avoid the side effect of the medicament on the skin and continuously maintain the stability of the property and the efficacy of the medicament.
Disclosure of Invention
Based on the above problems in practical use, the present invention aims to provide an external preparation for controlling parasitic infection of animals. The composition has broad spectrum of insecticidal activity, no adverse reaction of external preparation to skin, and long-lasting stability.
In order to achieve the purpose, the technical scheme of the invention is as follows: the external preparation containing the pharmaceutical composition of the isoxazoline and the macrolide is provided, and comprises the isoxazoline compound, the macrolide compound, an acceptable liquid carrier vehicle and an antioxidant.
An external formulation for controlling parasitic infestation in an animal comprising an isoxazoline compound, an acceptable liquid carrier vehicle, an antioxidant.
Preferably, the antioxidant is 3-dehydroshikimic acid.
More preferably, the antioxidant may be 3-dehydroshikimic acid or a combination of 3-dehydroshikimic acid with one or more of 2-phenyl chromone, vitamin E, beta-carotene, ascorbic acid, inositol phosphate, hydroxytyrosol, pinoresinol, catechins.
The isoxazoline compound in the external preparation is selected from one or more of fluroradine, alforadine, saroradine and loratadine.
The liquid carrier medium is solvent and cosolvent, and the solvent is one or more of dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether, dipropylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, and propylene glycol monobutyl ether. The cosolvent is one or more selected from dimethylformamide, N-dimethylacetamide, dimethylpropionamide, diethylformamide, dimethyl sulfoxide, diisopropylformamide, acetone, ethanol and isopropanol.
The external preparation is a compound of various types of medicinal compounds, can be combined with a macrolide compound to expand the broad spectrum of antibiosis, and the macrolide compound can be selected from one or more of ivermectin, moxidectin, milbemycin, selamectin, emamectin, latidectin or lepimectin.
The external preparation contains 10-200 mg/ml of isoxazoline compounds and 10-60 mg/ml of macrolide compounds according to the ratio of mass to total volume (w/v) of the external preparation.
Preferably, the external preparation contains 50-160 mg/ml of isoxazolines compound and 20-50 mg/ml of macrolide compound according to the ratio of mass to total volume (w/v) of the external preparation.
More preferably, the external preparation also comprises 0.5-2.0 mg/ml of 3-dehydroshikimic acid according to the ratio of the mass to the total volume of the external preparation; the dosage of the solvent accounts for 85-95% of the total volume of the preparation solution, and the dosage of the cosolvent accounts for 5-15% of the total volume of the preparation solution.
The invention relates to a preparation method of an external preparation for controlling animal parasitic infection, which comprises the following specific steps: taking the isoxazoline compound, the macrolide compound and the antioxidant according to the prescription amount, adding the cosolvent, then adding 80 percent of the amount of the solvent, controlling the temperature to be 30-40 ℃, clarifying, then adding the residual solvent, and filling into a low molecular weight polyethylene sealing tank to obtain the low molecular weight polyethylene.
Butylated Hydroxytoluene (BHT), also known as dibutylhydroxytoluene (But), as referred to herein y lated H y dox y Toluene) is also called 2, 6-di-tert-butyl-p-cresol, is an antioxidant and preservative, has an anti-oxidation component of grease, and is easy to cause skin inflammation and allergy when being added excessively. The cosmetic ingredient review board has demonstrated that BHT concentrations in care products are typically less than 0.1%, that BHT is absorbed by the skin but does not enter the bloodstream, and that low concentrations of BHT are not sensitive and do not risk carcinogenesis.
The 3-dehydroshikimic acid (DHS) is an important intermediate product in the biosynthetic metabolic pathway of aromatic amino acids in microorganisms and plants. The 3-dehydroshikimic acid is also a very effective antioxidant, the activity of which is superior to that of some commercial antioxidants such as gallic acid, propyl gallic acid, butyl hydroxy anisole, butylated hydroxytoluene and the like, and the 3-dehydroshikimic acid has important application value.
The co-solvent, also known as a co-solvent, is an auxiliary solvent that enhances the solubility of the primary solvent in solution. Most of the co-solvents are organic solvents themselves, but the addition of a small amount increases the solvency of the main solvent. Is commonly used for preparing missible oil and oil solution to improve the concentration of effective components of the missible oil and the oil solution. Especially, when preparing high-concentration emulsifiable oil and ultra-low volume oil, a certain cosolvent needs to be selected.
The external preparation for controlling animal parasitic infection provided by the invention has the following advantages:
1. the combined solvent is adopted, and the cosolvent increases the dissolution of the solvent to the medicine, thereby being beneficial to improving the content of effective substances of the preparation and the stability of the preparation.
2. The antioxidant such as 3-dehydroshikimic acid (DHS) is adopted, the irritation is small, the side effect and the harm are not caused by increasing the dosage, the compatibility with component solvents and effective medicines is good, the inoxidizability of a medicinal preparation is improved, and the continuous stability is facilitated.
3. The cosolvent with reducibility and the natural antioxidant are selected to improve the stability of the external preparation, and transdermal experiments show that the external preparation has a transdermal promotion effect and has obvious parasite inhibition and killing effects.
Drawings
FIG. 1 plasma concentration-time curve of fraxidin after use of the product of example 1 of the present invention;
FIG. 2 plasma concentration-time curve of selamectin after using the product of example 1 of the present invention.
Detailed Description
The invention will now be further described by way of the following examples, which are not intended to limit the scope of the invention in any way. It will be understood by those skilled in the art that equivalent substitutions for the technical features of the present invention, or corresponding modifications, can be made within the scope of the present invention.
The instruments, reagents, materials and the like used in the present examples are conventional instruments, reagents, materials and the like in the prior art and are commercially available in the normal market unless otherwise specified, and the experimental methods, detection methods and the like used in the following examples are conventional experimental methods, detection methods and the like in the prior art unless otherwise specified.
EXAMPLES 1-5 preparation of external preparation composition for controlling parasite infestation in animals having different composition according to the method of the present application
Example 1
Active ingredients: 1000mg of fluranide and 300mg of selamectin
Solvent: 8.5ml of dipropylene glycol monoethyl ether
Co-solvent: n, N-Dimethylacetamide 1.5ml
Antioxidant: 3-Dehydroshikimic acid 10mg
The preparation method comprises the following steps: taking the prescribed amount of the fluranide, the selamectin and the 3-dehydroshikimic acid, adding 1.5ml of N, N-dimethylacetamide, adding 80 percent of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, adding the residual solvent after clarification, and filling into a low molecular weight polyethylene sealed tank to obtain the finished product.
Example 2
Active ingredients: 800mg of flurarana, 240mg of selamectin
Solvent: dipropylene glycol monoethyl ether 9ml
Co-solvent: n, N-Dimethylacetamide 1ml
Antioxidant: 3-Dehydroshikimic acid 8mg
The preparation method comprises the following steps: taking the prescribed dose of the frataxin, the selamectin and the 3-dehydroshikimic acid, adding 1ml of N, N-dimethylacetamide, adding 80% of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the residual solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Example 3
Active ingredients: 1200mg of flurarana and 360mg of selamectin
Solvent: dipropylene glycol monoethyl ether 9.5ml
Co-solvent: n, N-dimethylacetamide 0.5ml
Antioxidant: 3-dehydroshikimic acid 12mg
The preparation method comprises the following steps: taking the fluranide, the selamectin and the 3-dehydroshikimic acid according to the prescription amount, adding 1ml of N, N-dimethylacetamide, adding 80% of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, adding the residual solvent after clarification, and filling into a low molecular weight polyethylene sealed tank to obtain the finished product.
Example 4
Active ingredients: saralana 100mg, selamectin 300mg
Solvent: dipropylene glycol monoethyl ether 9ml
Co-solvent: n, N-Dimethylacetamide 1ml
Antioxidant: 3-dehydroshikimic acid 10mg
The preparation method comprises the following steps: taking saraladine, selamectin and 3-dehydroshikimic acid according to the prescription amount, adding 1ml of N, N-dimethylacetamide, adding 80% of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the residual solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Example 5
Active ingredients: 1000mg of fluranide and 100mg of moxidectin
Solvent: dipropylene glycol monoethyl ether 9ml
Co-solvent: n, N-Dimethylacetamide 1ml
Antioxidant: 3-dehydroshikimic acid 10mg
The preparation method comprises the following steps: taking the prescribed amount of the fluranide, the moxidectin and the 3-dehydroshikimic acid, adding 1ml of N, N-dimethylacetamide, adding 80% of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the residual solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the finished product.
EXAMPLE 6 preparation of different Components of the composition for external preparation for controlling animal parasite infestations
Comparative example 1
Active ingredients: flurania 100mg, selamectin 300mg
Solvent: 10ml of dipropylene glycol monoethyl ether
The preparation method comprises the following steps: taking the prescribed amount of the frataxin and the selamectin, adding 80 percent of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, adding the residual solvent after clarification, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Comparative example 2
Active ingredients: 1000mg of fluranide and 300mg of selamectin
Solvent: 10ml of dipropylene glycol monoethyl ether
Antioxidant: butylated hydroxytoluene 1mg
The preparation method comprises the following steps: taking the prescribed amount of the frataxin, the selamectin and the butylated hydroxytoluene, adding 80 percent of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, fixing the volume and filling into a low molecular weight polyethylene sealing tube to obtain the low molecular weight polyethylene.
Comparative example 3
Active ingredients: 1000mg of fluranine and 300mg of selamectin
Solvent: dipropylene glycol monoethyl ether 8.5ml
Co-solvent: n, N-Dimethylacetamide 1.5ml
The preparation method comprises the following steps: taking the prescribed amount of the frataxin and the selamectin, adding 80 percent of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, adding 1.5ml of N, N-dimethylacetamide, clarifying, adding the rest solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Comparative example 4
Active ingredients: 1000mg of fluranine and 300mg of selamectin
Solvent: 10ml of dipropylene glycol monoethyl ether
Antioxidant: 3-dehydroshikimic acid 10mg
The preparation method comprises the following steps: taking the prescribed dose of the frataxin, the selamectin and the 3-dehydroshikimic acid, adding 80 percent of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the residual solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Comparative example 5
Active ingredients: sarolana 100mg, selamectin 300mg
Solvent: dipropylene glycol monoethyl ether 300ml
The preparation method comprises the following steps: taking saraladine and selamectin according to the prescription amount, adding 80% of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the residual solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Comparative example 6
Active ingredients: sarolana 100mg, selamectin 300mg
Solvent: 10ml of dipropylene glycol monoethyl ether
Antioxidant: butylated hydroxytoluene 1mg
The preparation method comprises the following steps: taking saraladine, selamectin and butylated hydroxytoluene according to the prescription amount, adding 80% of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the residual solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Comparative example 7
Active ingredients: saralana 100mg, selamectin 300mg
Solvent: dipropylene glycol monoethyl ether 9ml
Co-solvent: n, N-Dimethylacetamide 1ml
The preparation method comprises the following steps: taking saroradine and selamectin according to the prescription amount, adding 1ml of N, N-dimethylacetamide, adding 80% of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the residual solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Comparative example 8
Active ingredients: saralana 100mg, selamectin 300mg
Solvent: 10ml of dipropylene glycol monoethyl ether
Antioxidant: 3-dehydroshikimic acid 10mg
The preparation method comprises the following steps: taking saraladine, selamectin and 3-dehydroshikimic acid according to the prescription amount, adding 80 percent of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the residual solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Comparative example 9
Active ingredients: 1000mg of fluranine and 100mg of moxidectin
Solvent: 10ml of dipropylene glycol monoethyl ether
The preparation method comprises the following steps: taking the prescribed amount of the fraxidin and the moxidectin, adding 80 percent of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, adding the residual solvent after clarification, and filling into a low molecular weight polyethylene sealing tank to obtain the composition.
Comparative example 10
Active ingredients: 1000mg of fluranine and 100mg of moxidectin
Solvent: 10ml of dipropylene glycol monoethyl ether
Antioxidant: butylated hydroxytoluene 8mg
The preparation method comprises the following steps: taking the prescribed amount of the frataxin, the moxidectin and the butylated hydroxytoluene, adding 80 percent of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the rest solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Comparative example 11
Active ingredients: 1000mg of fluranide and 100mg of moxidectin
Solvent: dipropylene glycol monoethyl ether 9ml
Co-solvent: n, N-Dimethylacetamide 1ml
The preparation method comprises the following steps: taking the prescribed amount of the fraxidin and the moxidectin, adding 1ml of N, N-dimethylacetamide, adding 80% of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the rest solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the low molecular weight polyethylene.
Comparative example 12
Active ingredients: 1000mg of fluranide and 100mg of moxidectin
Solvent: 10ml of dipropylene glycol monoethyl ether
Antioxidant: 3-Dehydroshikimic acid 16mg
The preparation method comprises the following steps: taking the prescribed amount of fluranide, moxidectin and 3-dehydroshikimic acid, adding 80% of dipropylene glycol monoethyl ether, controlling the temperature to be 30-40 ℃, clarifying, adding the residual solvent, and filling into a low molecular weight polyethylene sealed tank to obtain the finished product.
Example 7 stability test
The solutions of the external preparations of examples 1 to 5 and comparative examples 1 to 12 were placed in a constant temperature and humidity cabinet having a temperature of 40 ± 2 ℃ and a relative humidity RH of 75% ± 5%, and sampled at the end of 3 months and 6 months, respectively, to determine their properties and contents. The results are shown in tables 1 to 3:
TABLE 1 accelerated test results for 3 and 6 months for topical solutions
TABLE 2 accelerated 3 month and 6 month test results for topical solutions
TABLE 3 accelerated test results for 3 and 6 months for topical solutions
As can be seen from tables 1 to 3, the external preparation has stable content after accelerated experiments, and the stability of the external preparation using a reducing solvent and 3-dehydroshikimic acid is superior to that of butylated hydroxytoluene by comparing the HPLC purity of a plurality of isoxazoline and macrolide compounds, and the stability of the external preparation using the reducing solvent and 3-dehydroshikimic acid is optimal, so that the HPLC purity of fluranine and selamectin is basically consistent under the condition of accelerating for 6 months.
The composite preparation of isoxazoline and macrolide with stable content can be obtained through the current prescription, the insecticidal effect is better than that of other marketed products through comparison of efficacy experiments, meanwhile, the use of artificially synthesized antioxidants is avoided, and the composite preparation is suitable for future commercial production.
Example 8 evaluation test of efficacy of insect repellent in Compound drop for external use
(1) In vitro insect repellant (tick)
In this evaluation, beagle dogs of mixed sex were used and assigned to the blank control group, the commercially available positive group and the groups of examples 1 to 3 of the present invention, and the test dogs were infested with 50 uneaten adult ticks (rhipicephalus sanguineus).
Dogs received treatment at a dose of 40mg/kg b.w. fluranide and 6mg/kg b.w. selamectin on day 0. The formulation was administered using a pipette. The dose is administered in the form of a line at the back neck of the skull base.
The average detection rate of each group of drugs for ticks in vitro was counted on days 0, 5, 10, 20 and 30 after administration, and any immediate response to treatment was observed on days 1, 2 and 7 after administration of the treatment, as well as adverse reactions, skin irritation and characteristics of the test formulations after treatment.
TABLE 4 average detection rate of drugs on dog ticks in vitro
(2) Expelling parasites in vivo
In this evaluation, beagle dogs of mixed sexes were used and assigned to a blank control group, a commercially available positive group and an experimental group, and experimental dogs were found to be infected with a large number of intestinal parasites (including hookworm, whipworm, roundworm, tapeworm, etc.) by microscopic examination using a laboratory stool-floating method and a direct smear method.
Dogs received treatment at a dose of 40mg/kg b.w. fluranide and 6mg/kg b.w. selamectin on day 0. The formulation was administered using a pipette. The dose is administered in the form of a line at the back neck at the base of the skull.
The average detection rates of each group of drugs for nematodes and tapeworms in dogs were counted on days 0, 5, 10, 20 and 30 after administration, and any immediate response to treatment was observed on days 1, 2 and 7 after administration of the treatment, as well as adverse reactions, skin irritation and the properties of the test formulations after treatment.
TABLE 5 detection rates of canine endoparasites for drugs
As can be seen from the table, the invention has obvious insecticidal effect on parasites in vivo and in vitro of dogs, the detection rate is lower than that of a blank control group and a commercial positive group, the action time is long, and the in vivo and in vitro insect expelling effect is still good in 30 days. The test result shows that the long-acting external liquid preparation for controlling animal parasite infection prepared by the embodiment of the invention has good parasite expelling and killing effects on parasites inside and outside the dog body within 30 days.
Example 9 blood concentration detection test
A single transdermal administration of a compound preparation based on flufrainer and selamectin to dogs was carried out, wherein flufrainer (40 mg/kg b.w.) and selamectin (6 mg/kg b.w.) were administered, and local and systemic tolerance of the dogs to the treatment was observed and the cosmetic appearance of the administration site was evaluated. Plasma samples were collected from all dogs on day 0, day 1, day 3, day 5, day 7 and then weekly through day 35, before and 2 hours, 4 hours, 8 hours after dosing. Plasma was analyzed for fluoride ralana and selamectin concentrations.
As a result: the mean plasma concentrations of fluranide and selamectin in dogs are shown in figures 1, 2, with no local or systemic adverse effects observed. The cosmetic appearance was acceptable.
EXAMPLE 10 safety test
About 20g of Kunming white mice are selected and randomly divided into 4 groups of 10 mice each with half of male mice and half of female mice. Group 1 was a control group, and 0.5m1 physiological saline was injected intramuscularly; the groups 2 to 4 are experimental groups, different doses (high dose, medium dose and low dose) of the long-acting compound anthelmintic liquid preparation disclosed by the embodiment of the invention are selected for preparation, 5.0mL, 3.0mL and 1.0mL of the long-acting compound anthelmintic liquid preparation are injected into muscles for 1 time, then the long-acting compound anthelmintic liquid preparation is continuously observed for 3 to 5 months, the eating, drinking, behavior change and death conditions of the mice are recorded during the period, 3 mice in each group are randomly selected for dissection after the experiment is finished, and the pathological changes of organs are observed and recorded.
As a result: the mice in the control group and the 2-4 groups have no death, normal food intake and water drinking and no obvious abnormal behavior in the test period, and the mice in the 2-4 groups have no abnormal pathological changes in the heart, liver, spleen, lung, kidney, stomach and intestinal tract and have no obvious difference with the control group through autopsy. The result shows that the long-acting external liquid preparation for controlling animal parasite infection is safe to use.
Claims (10)
1. An external preparation for controlling parasite infestation in animals, comprising a pharmaceutically effective ingredient which is an isoxazoline compound and/or a macrolide compound, a liquid carrier vehicle and an antioxidant comprising 3-dehydroshikimic acid.
2. The external preparation for controlling parasite infestations of animals according to claim 1, wherein said antioxidant is 3-dehydroshikimic acid or a combination of 3-dehydroshikimic acid with one or more of 2-phenylchromone, vitamin E, beta-carotene, ascorbic acid, inositol phosphate, hydroxytyrosol, pinoresinol, catechin.
3. The external preparation for controlling animal parasite infestation according to claim 1, wherein the isoxazolines are selected from one or more of frataxin, alfradine, sarorana, and lotilamide.
4. The external formulation for controlling parasitic infestation in animals according to claim 1, wherein the liquid carrier vehicle comprises a solvent which is a mixture of one or more of dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether, dipropylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, and propylene glycol monobutyl ether.
5. The external formulation for controlling parasitic infestation of animals according to claim 4 wherein the liquid carrier vehicle further comprises a co-solvent selected from the group consisting of mixtures of one or more of dimethylformamide, N-dimethylacetamide, dimethylpropionamide, diethylformamide, dimethylsulfoxide, diisopropylformamide, acetone, ethanol, isopropanol.
6. The topical formulation for controlling parasitic infections in animals according to claim 1, wherein the macrocyclic lactone compound is a combination of one or more of ivermectin, moxidectin, milbemycin, selamectin, emamectin, latidectin, or lepimectin.
7. The external preparation for controlling animal parasitic infection according to claim 1, wherein the external preparation contains 10 to 200mg/ml of isoxazolines and 10 to 60mg/ml of macrolides in terms of the ratio of mass to the total volume of the external preparation.
8. The external preparation for controlling parasitic infection of animals according to claim 7, wherein the external preparation contains 50 to 160mg/ml of the isoxazolines and 20 to 50mg/ml of the macrolide compound in terms of the ratio of the mass to the total volume of the external preparation.
9. The external preparation for controlling animal parasitic infection according to claim 8, wherein the external preparation further comprises 3-dehydroshikimic acid in an amount of 0.5 to 2.0mg/ml, based on the mass to total volume of the external preparation; the dosage of the solvent accounts for 85-95% of the total volume of the preparation solution, and the dosage of the cosolvent accounts for 5-15% of the total volume of the preparation solution.
10. A method for preparing an external preparation for controlling parasitic infestation of animals according to any one of claims 1 to 9, comprising the steps of: taking the isoxazoline compound, the macrolide compound and the antioxidant according to the prescription amount, adding the cosolvent, then adding 80 percent of the total amount of the solvent, controlling the temperature to be 30-40 ℃, clarifying, then adding the residual solvent, and filling into a low molecular weight polyethylene sealing tank to obtain the low molecular weight polyethylene.
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| US6426333B1 (en) * | 1996-09-19 | 2002-07-30 | Merial | Spot-on formulations for combating parasites |
| AU2016210773A1 (en) * | 2015-02-21 | 2016-09-29 | Othman Abdul Rahim Radi Al Hanbali | An anti-parasitic formulation and a method for treating parasitic infestations in an animal |
| CN110167540A (en) * | 2016-10-31 | 2019-08-23 | 斯克利普斯研究所 | For preventing the method and composition of the propagation of vector-borne disease |
| CN113038937A (en) * | 2018-09-05 | 2021-06-25 | 硕腾服务有限责任公司 | Palatable antiparasitic formulations |
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