CN116196322A - Pharmaceutical composition containing juglone and ivermectin for preventing and treating animal acariasis and application thereof - Google Patents
Pharmaceutical composition containing juglone and ivermectin for preventing and treating animal acariasis and application thereof Download PDFInfo
- Publication number
- CN116196322A CN116196322A CN202310131771.3A CN202310131771A CN116196322A CN 116196322 A CN116196322 A CN 116196322A CN 202310131771 A CN202310131771 A CN 202310131771A CN 116196322 A CN116196322 A CN 116196322A
- Authority
- CN
- China
- Prior art keywords
- ivermectin
- juglone
- pharmaceutical composition
- acariasis
- preventing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention belongs to the field of veterinary medicines, and in particular relates to a pharmaceutical composition for preventing or treating animal acariasis and application thereof, wherein the pharmaceutical composition is prepared by dissolving raw material medicines in an organic solvent, the raw material medicines comprise juglone and ivermectin, and the mass ratio of the juglone to the ivermectin is (1-10): (1-10); in the pharmaceutical composition, juglone and ivermectin are combined for the first time, and compared with a single dose, the pharmaceutical composition for treating animal acariasis has a synergistic effect in the aspect of acariasis killing, improves the control effect, reduces the loss caused by mites, promotes recovery of damaged fur, reduces fur damage, can avoid potential drug resistance caused by the use of a single compound, and reduces residues and environmental pollution.
Description
Technical Field
The invention belongs to the field of veterinary medicines, and particularly relates to a pharmaceutical composition containing juglone and ivermectin for preventing and treating animal acariasis and application thereof.
Background
Animal acariasis is a chronic ectoparasitic disease of animals, the pathogens of which are scabies and itch mites, mainly occur in late autumn, winter and early spring, and are infected by directly or indirectly contacting the diseased animals with healthy animals, and widely occur in animals such as cattle, sheep, horses, dogs, rabbits, chickens and the like, and can also be infected to people, and the infection rate and the incidence rate of the animal acariasis in pasture areas, agriculture and animal husbandry areas and large-scale farms are high. The occurrence of the disease of animals is mainly characterized by reduced appetite or abolished emaciation, severe itching, exudative dermatitis, dehairing and high infection, which seriously affect the production performance and economic value of the animals and severely restrict the healthy development and economic benefit of animal husbandry.
Currently, the drugs used for treating animal acariasis are mainly chemical synthesis and antibiotic drugs, and ivermectin is a high-efficiency broad-spectrum antibiotic antiparasitic agent. The mechanism of action is to interfere the nerve physiological activity of pests, stimulate and release gamma-aminobutyric acid, act on nerve and muscle joints, increase the release of chloride ions, inhibit the information transmission of the nerve joints, and cause the paralyzed and poisoned death of pests and mites. Ivermectin is widely applied to treatment of sheep mite diseases (see the literature such as Sha-Rua-Yi-Wei-mycin injection for treatment of sheep mite diseases [ J ]. Veterinary journal 2020 (21): 113.) and treatment of canine mite diseases (see the literature Guo Yuanyin and the like. The effect of ivermectin on canine mite diseases [ J ]. This day animal doctor 2021,37 (10): 95.) however, the long-term independent use is easy to generate drug resistance, so that the problems of increased dosage, reduced treatment effect, shortened duration and the like are unfavorable for public health, food safety, ecological environment and the like. For example, oral ivermectin injection for dogs shows poisoning symptoms after 5mL and 0.5h, and after arriving at the spot, the dogs are found to have symptoms of vomiting, ataxia, salivation in the mouth and mydriasis (see document Zhang Yong, etc. together, diagnosis of the dying case of ivermectin poisoning [ J ]. Shandong livestock veterinarian 2020,41 (04): 33 ]). The veterinary medicine in a pig farm increases the dose of ivermectin by 3-4 times, which leads to pig poisoning and death; however, it has also been shown that pigs are very resistant to ivermectin, injected subcutaneously at 5 doses per day, without typical toxic symptoms occurring after 5 days of continuous injection, at 8 doses at 6-8 days, and as a result, typical toxic symptoms occurring at 7 days, and death at 8 days (see, cao Kefei et al. Progress of ivermectin study on the control of parasitic diseases in pigs [ J ]. Jilin livestock veterinarian, 2020,41 (04): 3-5.). Meanwhile, with the use of ivermectin medicines in large quantities and even abuse in recent years, certain parasites generate certain drug resistance to the medicines, and the clinical insect repellent effect of ivermectin is seriously affected. Sheep digestive tract nematodes in natural pastures of inner Mongolian Hulun Bei Ermou have developed strong resistance to ivermectin and albendazole (see Luo Xiao, et al.3 anthelmintics have been studied for their killing effect against sheep gastrointestinal nematodes in inner Mongolian Hulun [ J ]. J.China veterinarian journal 2017,53 (10): 35-37.). The research also shows that the average infection rate of the gastrointestinal nematodes of 10 herd sheep in the eastern inner Mongolian region is as high as 79.2%, and the gastrointestinal nematodes of the 10 herd sheep are found to have different degrees of drug resistance to avermectin, ivermectin and albendazole after administration treatment, and only levamisole has good insect repellent effect on the gastrointestinal nematodes in the region (see the reference She Lede grid, etc. investigation of infection condition and drug resistance of sheep digestive tract nematodes in the Wuqi region [ J ]. Chinese veterinary science 2018,48 (06): 735-742). Therefore, the application of ivermectin is seriously affected by the drug resistance of ivermectin, and the technical problem to be solved by the person skilled in the art is how to reduce the drug resistance of ivermectin and increase the application range and effect of ivermectin.
Juglone (Juglone), chemical name is: 5-hydroxy-1, 4-naphthalenedione, belonging to the naphthoquinone class of compounds, CAS:481-39-0, molecular formula is C10H6O3. Juglone is an important active substance existing in juglans mandshurica and Juglans mandshurica belonging to Juglandaceae, and is a secondary metabolite generated in the long-term natural selection and evolution process of plants. Juglone can exert a variety of effects on cells, including DNA damage, inhibition of transcription, reduction of ph3 protein levels, induction of cell death, and the like. At present, juglone is mainly used for treating liver cancer (see patent CN 108703964A), gastric cancer (see patent Pingping and the like, the influence of juglone on proliferation, invasion and glycolysis of gastric cancer SGC-7901 [ J ]. Chinese medical science 2022,29 (05): 761-766.), lung cancer (see patent Hao Xinping, liu Zuoning. The influence of juglone on lung cancer NCL-H460 cells [ J ]. Proc. Ic. Medical college), 2022,44 (03): 181-183.DOI:10.16846/J. Issn.1004-3101.2022.03.005.) and cervical cancer (see patent Zhao Hangyu and the like, the juglone inhibits growth of cervical cancer cells and promotes apoptosis by promoting c-Myc ubiquitination [ J ]. A medical college, 2022,42 (07-1031.). 1026) has only disclosed therapeutic effects on tetranychup on mites (see patent Liu Yan and the like, the toxicity of juglone on tetranychup in green walnut skin is [ DOI:10.16846/J. Issn.1004-3101.2022.03.005 ]) and the treatment of cervical cancer (see patent No. DOI: 10.8248). It is known to researchers in the field that tetranychus cinnabarinus belongs to plant mites, chemical pesticides are mainly used for controlling and the effect of juglone on controlling animal mite diseases is not disclosed in any literature, unlike controlling animal mite diseases. Nor does it disclose that juglone and ivermectin are used in combination to provide a synergistic effect.
Aiming at the technical problems, the juglone 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 acariasis killing, improves the control effect, reduces the loss caused by mites, promotes the recovery of damaged fur, reduces the fur damage, can avoid potential drug resistance caused by the use of a single compound, and reduces the residue and environmental pollution.
Disclosure of Invention
The invention aims to solve the problems in the prior art, and provides a pharmaceutical composition for preventing or treating animal acariasis, which is used for treating animal acariasis and has the advantages of obvious synergistic effect, long duration and environmental friendliness. The specific technical scheme is as follows:
the primary object of the invention is to provide a pharmaceutical composition for preventing or treating animal acariasis, which comprises juglone and ivermectin, wherein the mass ratio of the juglone to the ivermectin is (1-10): (1-10).
Preferably, the pharmaceutical composition consists of juglone and ivermectin, and the mass ratio of the juglone to the ivermectin is (1-10): (1-10).
Preferably, the mass ratio of the juglone to the ivermectin is (1-5): (1-10).
Preferably, the mass ratio of the juglone to the ivermectin is 1:10.
preferably, the mass ratio of the juglone to the ivermectin is 1:1.
preferably, the mass ratio of the juglone to the ivermectin is 5:1.
preferably, the mites include one or more of itch mites and scabies mites.
Preferably, the mites are rabbit itch mites.
Preferably, the composition for treating animal acariasis is prepared into powder, injection, external ointment, emulsion and spray by adding pharmaceutically acceptable auxiliary materials.
The second object of the invention is to provide the application of the pharmaceutical composition in preparing medicines for preventing animal acariasis.
The third object of the invention is to provide the application of the pharmaceutical composition in preparing medicines for treating animal acariasis.
The beneficial effects of the invention are as follows: in the pharmaceutical composition, juglone and ivermectin are combined for the first time, and compared with a single dose, the pharmaceutical composition for treating animal acariasis has a synergistic effect in the aspect of acariasis killing, improves the control effect, reduces the loss caused by mites, promotes the recovery of damaged fur, reduces the fur damage, obviously reduces the administration dosage of ivermectin, can avoid potential drug resistance caused by the use of a single compound, and reduces the residue and environmental pollution.
Detailed Description
The foregoing is further elaborated upon by the following detailed description of the invention in order to provide a better understanding of the invention. But this should not be construed as limiting the invention.
The experiments disclosed by the invention are not specially described, and all the experiments adopt a conventional method;
the drugs according to the present invention are commercially available without any particular explanation.
In the examples of the present invention, DMSO is used as a vehicle to promote dissolution of the drug, however, those skilled in the art will appreciate that vehicles used in the art to achieve dissolution of the drug are applicable.
Example 1
The pharmaceutical composition of the invention is prepared as follows:
mixing 500 μg juglone and 500 μg ivermectin, dissolving in 100 μl dimethyl sulfoxide, mixing well, adding water to 10mL, and fixing volume to obtain the final product.
Example 2
The pharmaceutical composition of the invention is prepared as follows:
167 mug juglone and 835 mug ivermectin are mixed, dissolved in 100 mug dimethyl sulfoxide, evenly mixed, then added with water to 10mL, and the volume is fixed, thus obtaining the compound.
Example 3
The pharmaceutical composition of the invention is prepared as follows:
mixing 90.9 μg juglone and 909.9 μg ivermectin, dissolving in 100 μl dimethyl sulfoxide, mixing uniformly, adding water to 10mL, and fixing volume to make it uniform.
Example 4
The pharmaceutical composition of the invention is prepared as follows:
mixing 835 μg juglone and 167 μg ivermectin, dissolving in 100 μl dimethyl sulfoxide, mixing uniformly, adding water to 10mL, and fixing volume to make it uniform.
Example 5
The pharmaceutical composition of the invention is prepared as follows:
909.9 μg juglone and 90.9 μg ivermectin are mixed, dissolved in 100 μl dimethyl sulfoxide, uniformly mixed, then added with water to 10mL, and the volume is fixed, so that the compound is obtained.
EXAMPLE 6 determination of acaricidal Activity of juglone and ivermectin compositions against Rabbit itch mites
1. Experimental methods and materials
Collecting white rabbits of New Zealand with natural itch mite disease from a farm, collecting itch mites, and culturing at 25+ -1deg.C with RH not less than 80%. The test mites were used only once and then sacrificed with boiling water.
Experimental grouping: a medicine composition group, a juglone group, an ivermectin group and a 1% dimethyl sulfoxide group with different proportions.
The experimental method comprises the following steps: after diluting the drug with water, 0.35ml of the drug solution was taken to soak the bottom of the dish with filter paper sheets therein, and 1% DMSO solution was used as the solvent control. And (3) picking mites to the center of a filter paper sheet in the dish by using a picking needle, sealing, culturing in an incubator (25+/-1 ℃ and RH is more than or equal to 80%) for 24 hours, and counting the death number under a microscope, wherein the death number is regarded as death after the death is still. The experiment was performed in triplicate.
Compounding synergy of acaricides EC of the mixture was calculated according to the Wadley method 50 . According to individual doses EC 50 The values, proper preliminary screening concentration, are selected, and the in vitro mite killing activity screening of the mixture is carried out according to the mass ratio (active component A: active component B) of 1:1, 1:5, 1:10, 10:1 and 5:1. Finally, calculating the synergy coefficient and SR of the mixed different medicaments by a Wadley formula>1.5 is synergy; SR (SR)<0.5 is antagonism; an SR between 0.5 and 1.5 indicates an additive effect.
1％DMSO
2. Experimental results
Table 1 acaricidal activity of juglone and ivermectin compositions
As can be seen from the results in table 1, the synergistic effect of the juglone and ivermectin mixed in the ratio of 1:1, 1:10 and 5:1 is obvious, the synergistic effect coefficient SR is greater than 1.5, wherein the synergistic effect coefficient of the juglone and the ivermectin mixed in the ratio of 1:10 is the highest, and the juglone and the ivermectin mixed in the ratio of 1:5 and 10:1 are added.
In summary, the juglone and ivermectin are combined for the first time, the prepared pharmaceutical composition has high mortality rate on mites, has good treatment effect on animal acariasis caused by itch mites and scabies, and compared with a single dose, the pharmaceutical composition for treating animal acariasis has synergistic effect in the aspect of mite killing when being combined with the single dose, improves the control effect, reduces the loss caused by mites, promotes recovery of damaged fur, reduces the fur damage, can avoid potential drug resistance caused by the use of a single compound, reduces residues and environmental pollution, and also reduces the dosage of chemically synthesized active ingredients. In addition, the composition is safe to animals and meets the requirement of safety.
Claims (10)
1. A pharmaceutical composition for preventing or treating acariasis in animals, which is characterized by comprising juglone and ivermectin, wherein the mass ratio of the juglone to the ivermectin is (1-10): (1-10).
2. The pharmaceutical composition for preventing or treating animal acariasis according to claim 1, which is composed of juglone and ivermectin in a mass ratio of (1-10): (1-10).
3. The pharmaceutical composition for preventing or treating animal acariasis according to claim 2, wherein the mass ratio of juglone to ivermectin is (1-5): (1-10).
4. A pharmaceutical composition for preventing or treating acariasis in animals according to claim 3, wherein the mass ratio of juglone to ivermectin is 1:10.
5. a pharmaceutical composition for preventing or treating acariasis in animals according to claim 3, wherein the mass ratio of juglone to ivermectin is 1:1.
6. a pharmaceutical composition for preventing or treating animal acariasis according to claim 3, characterized in that the mass ratio of juglone to ivermectin is 5:1.
7. a pharmaceutical composition for preventing or treating animal acariasis according to any one of claims 1 to 6, wherein the mites include one or more of itch mites and scabies.
8. The pharmaceutical composition for preventing or treating animal acariasis according to any one of claims 1 to 6, which is formulated into powder, injection, topical ointment, emulsion, spray by adding pharmaceutically acceptable adjuvants.
9. Use of a pharmaceutical composition according to any one of claims 1-6 for the preparation of a medicament for the prevention of acariasis in animals.
10. Use of a pharmaceutical composition according to any one of claims 1-6 for the preparation of a medicament for the treatment of acariasis in animals.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310131771.3A CN116196322A (en) | 2023-02-18 | 2023-02-18 | Pharmaceutical composition containing juglone and ivermectin for preventing and treating animal acariasis and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310131771.3A CN116196322A (en) | 2023-02-18 | 2023-02-18 | Pharmaceutical composition containing juglone and ivermectin for preventing and treating animal acariasis and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116196322A true CN116196322A (en) | 2023-06-02 |
Family
ID=86516826
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310131771.3A Pending CN116196322A (en) | 2023-02-18 | 2023-02-18 | Pharmaceutical composition containing juglone and ivermectin for preventing and treating animal acariasis and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116196322A (en) |
-
2023
- 2023-02-18 CN CN202310131771.3A patent/CN116196322A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MacAllister et al. | Effects of omeprazole paste on healing of spontaneous gastric ulcers in horses and foals: a field trial | |
| CN100586441C (en) | Compound sulfamonomethoxine sodium injection and preparation method thereof | |
| US20150132390A1 (en) | Pathogenic attenuation via the administration of an equilibiotic compound | |
| US6992073B2 (en) | Use of N-acetyl-D-glucosamine in the manufacture of a medicament for treating cervical erosion | |
| CN116196322A (en) | Pharmaceutical composition containing juglone and ivermectin for preventing and treating animal acariasis and application thereof | |
| RU2473334C2 (en) | Anti-eimeriosis pharmaceutical composition based on salt of quarternary phosphonium and substituted dinitrobenzofuroxane | |
| CN115645417A (en) | Application of chenodeoxycholic acid in preparation of medicine or feed additive for treating or preventing porcine viral diarrhea | |
| CN115887479A (en) | Pharmaceutical composition containing eugenol and ivermectin for preventing and treating animal acariasis and application thereof | |
| CN109432106B (en) | Compound sulfachlorpyridazine and preparation method thereof | |
| RU2412698C1 (en) | Method of treating helminthiases in ruminants and medicinal agent for implementation thereof | |
| CN116077514A (en) | Pharmaceutical composition containing thymol and ivermectin for preventing and treating animal acariasis and application thereof | |
| Borisenko et al. | The efficacy tests results of the veterinary drug" trifuzol 1% solution for injection" | |
| RU2356562C2 (en) | Anti parasite medication for treatment of dogs and cats | |
| RU2333759C1 (en) | Medication for treatment and prevention of postnatal cow endometritis and sow metritis-mastitis-agalactia | |
| RU2352344C2 (en) | Method of cows endometritis prevention | |
| Kabir et al. | Assessment of acaricidal efficacy of ivermectin against ectoparasitic skin lesions in goats | |
| US7704976B2 (en) | Use of N-acetyl-D-glucosamine for preparing medicines for urogenital tract infection's treatment and prevention | |
| RU2268040C2 (en) | Preparation for treating diarrhea in youngsters of farm animals and method for its application | |
| CN109908117B (en) | Medical application of compound pyromalnol in resisting neospora caninum | |
| RU2695069C1 (en) | Method for treating cattle in buxtonella disease | |
| US2797182A (en) | Cadmium anthranilate containing anthelmintics | |
| RU2320352C2 (en) | Method for treating subclinical mastitis in cows | |
| RU2140737C1 (en) | Agent for prophylaxis and treatment of animals with parasitic sicknesses | |
| RU2322235C1 (en) | Method for preventing and treating eimeriosis in animals and poultry | |
| RU2557889C1 (en) | Agent for treatment of coccidiosis in birds and animals |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |