CN115887479A - Pharmaceutical composition containing eugenol and ivermectin for preventing and treating animal acariasis and application thereof - Google Patents
Pharmaceutical composition containing eugenol and ivermectin for preventing and treating animal acariasis and application thereof Download PDFInfo
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- CN115887479A CN115887479A CN202310131758.8A CN202310131758A CN115887479A CN 115887479 A CN115887479 A CN 115887479A CN 202310131758 A CN202310131758 A CN 202310131758A CN 115887479 A CN115887479 A CN 115887479A
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- ivermectin
- eugenol
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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
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Abstract
The invention belongs to the field of medicines, and particularly relates to a pharmaceutical composition containing eugenol and ivermectin for preventing and treating animal acariasis and/or plant acariasis and an application thereof, wherein the pharmaceutical composition comprises eugenol and ivermectin, and the mass ratio of eugenol to ivermectin is (1-10): (1-10), in the pharmaceutical composition, eugenol and ivermectin are combined for the first time, and compared with a single dose, the composition for treating animal acariasis has a synergistic effect in the aspect of acaricidal action, improves the control effect, reduces the loss caused by acarids, and promotes the recovery of damaged fur. And drug resistance caused by the large-scale use of medicines such as ivermectin and the like can be avoided, and drug residue and environmental pollution are avoided.
Description
Technical Field
The invention belongs to the field of veterinary drugs, and particularly relates to a pharmaceutical composition containing eugenol and ivermectin for preventing and treating animal acariasis and application thereof.
Background
Animal acariasis is a chronic ectoparasitic disease of animals caused by the body surface of a mite-parasitized animal, the pathogeny of which is scabies mite and itch mite, mainly occurs in late autumn, winter and early spring, is infected by direct or indirect contact of the sick animal and a healthy animal, widely occurs in animals such as cattle, sheep, horses, dogs, rabbits, chickens and the like, can be infected by human beings, and has higher infection rate and morbidity in pasturing areas, farming areas and large-scale farms. The disease of animals mainly shows that the animals have the characteristics of reduced or abolished appetite, emaciation, severe itching, exudative dermatitis, depilation and high infection, the production performance and the economic value of the animals are seriously influenced, and the healthy development and the economic benefit of the animal husbandry are seriously restricted.
At present, the medicines for treating animal acariasis are mainly chemosynthesis and antibiotic medicines, and ivermectin is a high-efficiency broad-spectrum antibiotic antiparasitic agent. The action mechanism is to interfere the nerve physiological activity of pests, stimulate to release gamma-aminobutyric acid, act on nerve and muscle joints, increase the release of chloride ions, inhibit the information transmission of nerve joints and cause the pests and pest mites to be paralyzed and poisoned and killed. Ivermectin is widely applied to treatment of sheep mite diseases (see literatures such as a La. Ivermectin injection for treating sheep mite diseases [ J ]. Veterinary guidance, 2020 (21): 113.), and treatment of dog mite diseases (see literatures such as Guo Yuan Ying et al. Ivermectin has the effect of treating dog mite diseases [ J ]. Domestic animal husbandry and veterinary, 2021,37 (10): 95.), but the long-term single use is easy to generate drug resistance, so that the problems of increased dosage, reduced treatment effect, shortened lasting period and the like are caused, and the ivermectin is not beneficial to public health, food safety, ecological environment and the like. For example, dogs take 5mL of ivermectin injection orally and develop symptoms of intoxication, including vomiting, ataxia, dribbling in mouth, mydriasis, etc., after 0.5h (see Zhang Yong et al. Diagnosis and treatment of dying cases of ivermectin intoxication together [ J ]. Shandong zooveterinarian, 2020,41 (04): 33.). The resistance of pigs to ivermectin is strong, 5 times of dose of avermectin is injected subcutaneously every day, typical poisoning symptoms do not appear after 5 days of continuous injection, 8 times of dose is injected at 6-8 days, and as a result, typical poisoning symptoms appear at 7 days and death occurs at 8 days (see literature Cao Kefei et al, research progress of ivermectin on prevention and treatment of pig parasitic diseases [ J ] Jilin animal veterinarian, 2020,41 (04): 3-5.). Meanwhile, with the recent heavy use and even abuse of ivermectin drugs, certain parasites generate certain drug resistance to the drugs, and the clinical anthelmintic effect of ivermectin is seriously influenced. The ovine digestive tract nematodes in certain natural ranches of inner Mongolia Hulunbel developed stronger resistance to both ivermectin and albendazole (see the literature of Xiaoxiaping et al. 3 anthelmintics on the killing effect of gastrointestinal nematodes in ovine tracts in inner Mongolia Hull region [ J ]. Chinese veterinary J., 2017,53 (10): 35-37.). Therefore, the application of ivermectin is seriously influenced by the drug resistance of ivermectin, and how to reduce the drug resistance of ivermectin and increase the application range and effect of ivermectin is a technical problem to be solved by the technical personnel in the field.
Eugenol (Eugenol) has various pharmacological activities of resisting inflammation and inhibiting bacteria, relieving fever and easing pain, anaesthetizing, resisting oxidation and tumors, expelling parasites and killing mites and promoting transdermal absorption, and the like, and the Eugenol is disclosed to be used for treating animal mites (see the literature, the research on the mite killing efficacy and action mechanism of plum-carvacrol and Eugenol [ D ]. Guangxi university, 2021 ]), however, no literature discloses that the Eugenol and ivermectin have the synergistic effect, and the dosage of the ivermectin can be reduced, so that the drug resistance of the ivermectin is reduced.
The inventor proves through a large number of experimental studies that the pharmaceutical composition obtained by combining eugenol and ivermectin can achieve the synergistic effect, remarkably improve the control effect on animal acariasis, reduce the loss caused by acarids, promote the recovery of damaged fur and reduce the damage to fur. And potential drug resistance caused by the use of a single compound can be avoided, and residues and environmental pollution are reduced.
Disclosure of Invention
The invention aims to solve the problems in the prior art and provides a composition containing eugenol and ivermectin for treating animal acariasis, which has the advantages of obvious synergistic effect, long lasting period, low toxicity and environmental friendliness when used for treating animal acariasis. The specific technical scheme is as follows:
the invention aims to provide a pharmaceutical composition for preventing or treating animal acariasis, which comprises eugenol and ivermectin, wherein the mass ratio of the eugenol to the ivermectin is (1-10): (1-10).
Preferably, the pharmaceutical composition consists of eugenol and ivermectin, and the mass ratio of the eugenol to the ivermectin is (1-10): (1-10).
Preferably, the mass ratio of the eugenol to the ivermectin is (1-10): (1-5).
Preferably, the mass ratio of the eugenol to the ivermectin is 1:1.
preferably, the mass ratio of the eugenol to the ivermectin is 1:5.
preferably, the mass ratio of the eugenol to the ivermectin is 10:1.
preferably, the mites comprise one or more of itch mites and scabies mites.
Preferably, the composition for treating animal acariasis is added with pharmaceutically acceptable auxiliary materials to prepare powder, injection, external ointment, emulsion and spray.
The second purpose of the invention is to provide the application of the pharmaceutical composition in preparing the medicine for preventing the animal acariasis.
The third purpose of the invention is to provide the application of the pharmaceutical composition in preparing the medicine for treating animal acariasis.
The invention has the beneficial effects that: in the pharmaceutical composition, eugenol and ivermectin are combined for the first time, and compared with a single dose, the composition for treating animal acariasis has a synergistic effect in the aspect of killing acarids, improves the control effect, reduces the loss caused by acarids, promotes the recovery of damaged fur, and reduces the damage to the fur. And potential drug resistance caused by the use of a single compound can be avoided, and residues and environmental pollution are reduced.
Detailed Description
The foregoing and other aspects of the present invention will become more apparent from the following detailed description, given by way of example only, for purposes of illustrating the invention. This is not to be construed as limiting the invention.
The experiments disclosed by the invention are not specially explained, and all adopt a conventional method;
the drugs of the present invention are not specifically described, and are commercially available.
In the examples of the present invention, DMSO is used as a vehicle for promoting the dissolution of the drug, however, it will be understood by those skilled in the art that vehicles used in the art to achieve the dissolution of the drug may be used.
Example 1
The pharmaceutical composition of the invention is prepared as follows:
mixing 500 mu g of eugenol and 500 mu g of ivermectin, dissolving in 100 mu L of solvent such as dimethyl sulfoxide (DMSO), mixing uniformly, adding water to 10mL, and diluting to constant volume to obtain the final product.
Example 2
The pharmaceutical composition of the invention is prepared as follows:
mixing 167 μ g of eugenol and 835 μ g of ivermectin, dissolving in 100 μ g of solvent such as LDMSO, mixing well, adding water to 10mL, and diluting to constant volume to obtain the final product.
Example 3
The pharmaceutical composition of the invention is prepared as follows:
mixing 90.9 mu g of eugenol and 909.9 mu g of ivermectin, dissolving in 100 mu of solvent such as LDMSO, mixing uniformly, adding water to 10mL, and diluting to constant volume to obtain the final product.
Example 4
The pharmaceutical composition of the invention is prepared as follows:
mixing 835 μ g eugenol and 167 μ g ivermectin, dissolving in 100 μ g solvent such as LDMSO, mixing well, adding water to 10mL, and diluting to desired volume to obtain the final product.
Example 5
The pharmaceutical composition of the invention is prepared as follows:
mixing 909.9 μ g eugenol and 90.9 μ g ivermectin, dissolving in 100 μ g solvent such as LDMSO, mixing well, adding water to 10mL, and fixing volume to obtain the final product.
EXAMPLE 6 measurement of the acaricidal Activity of eugenol and ivermectin compositions against Primordia rabbit
1. Experimental methods and materials
Collecting New Zealand big ear white rabbits naturally infected with itch mite disease from a farm, collecting itch mite, and culturing at 25 + -1 deg.C and RH greater than or equal to 80%. Experimental test mites were used only once, after which they were killed with boiling water.
Grouping experiments: pharmaceutical composition group, eugenol group, ivermectin group, 1% DMSO.
The experimental method comprises the following steps: after dilution of the drug with water, the bottom of the dish with the filter paper discs was soaked with 0.35ml of the drug solution, and the solvent control employed 1% DMSO solution. Picking the mites to the center of a filter paper sheet in a plate by using a mite picking needle, sealing, culturing for 24 hours in an incubator (25 +/-1 ℃, RH is more than or equal to 80 percent), counting the death number under a microscope, and considering the mites as death when the mites are still. The experiment was performed in triplicate.
LC of the mixture is calculated according to the Wadley method for the mixed synergism of the acaricide 50 . According to each single dose LC 50 Selecting proper primary screening concentration, and carrying out in-vitro acaricidal activity screening on the mixture according to the mass ratio (active component A: active component B) of 1. Finally, calculating the synergistic coefficient, SR, of the mixed different medicaments by the Wadley formula>1.5 is synergy; SR<0.5 is antagonistic; an SR between 0.5 and 1.5 indicates additive effect.
2. Results of the experiment
TABLE 1 Digiferol and Ivermectin compositions having acaricidal Activity
| Medicament | Regression equation | LC 50 (μg/mL) | Confidence interval (95%) | SR |
| Eugenol (A) | Y＝2.12X-3.89 | 68.48 | 20.72-105.28 | / |
| Ivermectin (B) | Y＝1.18X-1.40 | 15.08 | 0.67-28.89 | / |
| A:B＝1:1 | Y＝0.531X-0.021 | 1.10 | 0.142-2.571 | 6.06 |
| A:B＝1:5 | Y＝0.441X+0.022 | 0.89 | 0.037-2.504 | 4.69 |
| A:B＝1:10 | Y＝1.048X-1.055 | 10.15 | 6.131-14.394 | 0.38 |
| A:B＝10:1 | Y＝0.77X-0.878 | 13.78 | 7.387-21.309 | 1.74 |
| A:B＝5:1 | Y＝0.862X-0.898 | 11.01 | 5.942-16.511 | 1.47 |
| 1％DMSO | -- | -- | -- | -- |
From the results in table 1, it can be seen that the eugenol and ivermectin have a significant synergistic effect in the mixing of 1, 5 and 10.
In conclusion, in the pharmaceutical composition, the eugenol and the ivermectin are combined for the first time, and compared with a single dose, the composition for treating the animal acariasis has a synergistic effect in the aspect of killing acarids, so that the control effect is improved, the loss caused by acarids is reduced, the recovery of damaged fur is promoted, and the damage to the fur is reduced. And potential drug resistance caused by the use of a single compound can be avoided, residues and environmental pollution are reduced, and the dosage of active ingredients for chemical synthesis is reduced. In addition, the composition is safe for animals and meets the requirement on safety.
Claims (10)
1. The pharmaceutical composition for preventing or treating animal acariasis is characterized by comprising eugenol and ivermectin, wherein the mass ratio of the eugenol to the ivermectin is (1-10): (1-10).
2. The pharmaceutical composition for preventing or treating acariasis in animals according to claim 1, wherein the pharmaceutical composition is composed of eugenol and ivermectin, and the mass ratio of eugenol to ivermectin is (1-10): (1-10).
3. The pharmaceutical composition for preventing or treating acariasis in animals according to claim 2, wherein the mass ratio of eugenol to ivermectin is (1-10): (1-5).
4. The pharmaceutical composition for preventing or treating acariasis in animals according to claim 3, wherein the mass ratio of eugenol to ivermectin is 1:1.
5. the pharmaceutical composition for preventing or treating acariasis in animals according to claim 3, wherein the mass ratio of eugenol to ivermectin is 1:5.
6. the pharmaceutical composition for preventing or treating acariasis in animals according to claim 3, wherein the mass ratio of eugenol to ivermectin is 10:1.
7. the pharmaceutical composition for preventing or treating acariasis in an animal according to any one of claims 1 to 6, wherein the acarids comprise one or more of itch mites and scabies mites.
8. The pharmaceutical composition for preventing or treating acariasis of animals according to any one of claims 1 to 6, wherein pharmaceutically acceptable auxiliary materials are added into the composition for treating acariasis of animals to prepare powder, injection, external ointment, emulsion and spray.
9. Use of a pharmaceutical composition according to any one of claims 1 to 6 for the manufacture of a medicament for the prevention of acariasis in an animal.
10. Use of a pharmaceutical composition according to any one of claims 1 to 6 for the manufacture of a medicament for the treatment of acariasis in an animal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310131758.8A CN115887479A (en) | 2023-02-18 | 2023-02-18 | Pharmaceutical composition containing eugenol and ivermectin for preventing and treating animal acariasis and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310131758.8A CN115887479A (en) | 2023-02-18 | 2023-02-18 | Pharmaceutical composition containing eugenol and ivermectin for preventing and treating animal acariasis and application thereof |
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| Publication Number | Publication Date |
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| CN115887479A true CN115887479A (en) | 2023-04-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN202310131758.8A Pending CN115887479A (en) | 2023-02-18 | 2023-02-18 | Pharmaceutical composition containing eugenol and ivermectin for preventing and treating animal acariasis and application thereof |
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| CN (1) | CN115887479A (en) |
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- 2023-02-18 CN CN202310131758.8A patent/CN115887479A/en active Pending
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