CN116725008A - Synergistic nano microemulsion of mouse sterilant and application thereof - Google Patents
Synergistic nano microemulsion of mouse sterilant and application thereof Download PDFInfo
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- CN116725008A CN116725008A CN202310472393.5A CN202310472393A CN116725008A CN 116725008 A CN116725008 A CN 116725008A CN 202310472393 A CN202310472393 A CN 202310472393A CN 116725008 A CN116725008 A CN 116725008A
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- synergistic
- sterilant
- microemulsion
- murine
- bait
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- 230000002195 synergetic effect Effects 0.000 title claims abstract description 101
- 239000004530 micro-emulsion Substances 0.000 title claims abstract description 61
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims abstract description 89
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 31
- 229940051841 polyoxyethylene ether Drugs 0.000 claims abstract description 30
- 229920000056 polyoxyethylene ether Polymers 0.000 claims abstract description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 18
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- ZIWRUEGECALFST-UHFFFAOYSA-M sodium 4-(4-dodecoxysulfonylphenoxy)benzenesulfonate Chemical compound [Na+].CCCCCCCCCCCCOS(=O)(=O)c1ccc(Oc2ccc(cc2)S([O-])(=O)=O)cc1 ZIWRUEGECALFST-UHFFFAOYSA-M 0.000 claims abstract description 16
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims abstract description 11
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- 238000001035 drying Methods 0.000 claims description 3
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
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- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 2
- 238000010790 dilution Methods 0.000 claims description 2
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- 229940079593 drug Drugs 0.000 abstract description 21
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- 235000013339 cereals Nutrition 0.000 description 13
- 229960001842 estramustine Drugs 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 11
- 238000012360 testing method Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000012449 Kunming mouse Methods 0.000 description 6
- 235000021329 brown rice Nutrition 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 235000019629 palatability Nutrition 0.000 description 6
- 239000000575 pesticide Substances 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000035935 pregnancy Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000008174 sterile solution Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical group ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 3
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- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 2
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 2
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- 239000000654 additive Substances 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
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- 231100000507 endocrine disrupting Toxicity 0.000 description 2
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- 229960002568 ethinylestradiol Drugs 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
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- 238000012986 modification Methods 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
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- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 239000004753 textile Substances 0.000 description 2
- 239000012224 working solution Substances 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 1
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- 239000000020 Nitrocellulose Substances 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
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- 230000000622 irritating effect Effects 0.000 description 1
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- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
- A01N25/04—Dispersions, emulsions, suspoemulsions, suspension concentrates or gels
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/30—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests characterised by the surfactants
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N45/00—Biocides, pest repellants or attractants, or plant growth regulators, containing compounds having three or more carbocyclic rings condensed among themselves, at least one ring not being a six-membered ring
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P23/00—Chemosterilants
-
- 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
Abstract
The invention discloses a synergistic nano-microemulsion of a mouse sterilant and application thereof, wherein the synergistic nano-microemulsion of the sterilant comprises span80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, diethylene glycol, hydrogenated castor oil polyoxyethylene ether and water, and the volume ratio of span80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, diethylene glycol, hydrogenated castor oil polyoxyethylene ether and water is 10-20:20-50:20-50:1000-2000. The synergistic nano microemulsion of the sterilant used in the invention reduces the dosage of the mouse sterilant by about 50%, saves the cost, reduces the environmental residue of the drug and reduces the danger to other non-target organisms.
Description
Technical Field
The invention belongs to the technical field of mouse sterilant, and in particular relates to a synergistic nano microemulsion of a mouse sterilant and application thereof.
Background
The current control of the mouse injury mainly depends on chemical killing mainly based on anticoagulant, but the problems of short control effect, easy population rebound, natural enemies injury, environmental pollution, drug resistance and the like are increasingly serious, and adverse effects are generated on non-target species and human safety. The study of sterility technology is carried out by the students in China from the end of the last 50 th century, and the sterilant such as ethinyl estrone, cabergoline, chlordydrogesterone acetate and the like with application potential is screened out, and the physiological mechanism and sterility effect of the sterilant are studied deeply. However, the application of the anticoagulant or the sterilant requires the delivery of active ingredients through the bait, so that the palatability of the bait plays a key role in the efficacy, the bait with good palatability improves the utilization rate of the bait, and the pollution of the drug to the environment is reduced. However, the problems of poor palatability of the endocrine disrupting sterilant such as the propargyl estrane exist, for example, huang Maoshu and the black-edge dentate mice have lower intake of the propargyl estrane drug bait prepared by a soaking method and an adhesion method respectively, and on the other hand, the endocrine disrupting sterilant is indissolvable in water, and the prepared drug bait has the problems of uneven dispersion and adhesion of drugs, low effective dose and the like, so that the drugs are wasted and abused. In practice, by means of changing the ingredients of the base bait, adding additives, changing the preparation method of the bait and the like in the preparation of the bait, the palatability of the bait is improved, the intake of the bait by the mice is increased, and the permeation and adsorption of the drug are improved, so that the effective dosage of the drug in the bait is increased. Commonly used pesticides penetrate co-solvents such as dimethylformamide, but they have a irritating effect on the eyes, skin and respiratory tract. Can cause light and moderate irritation symptoms of upper respiratory tract. The polluted skin can cause light and heavy burns, liver damage is more prominent in acute poisoning, and residues of the skin can cause environmental pollution, so that potential safety hazards are caused to non-target animals. Therefore, development of a high-efficiency, low-toxicity and environment-friendly synergist is needed to improve the utilization rate of the sterilant and realize the reduction and synergy of pesticides and fertilizers.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a synergistic nano microemulsion of a murine sterilant and application thereof in preparing a murine bait material. The synergistic nano microemulsion of the sterilant used in the invention reduces the dosage of the mouse sterilant by about 50%, saves the cost, reduces the environmental residue of the drug and reduces the danger to other non-target organisms.
The invention provides a synergistic nano microemulsion of a mouse sterilant, which comprises span80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, diethylene glycol, hydrogenated castor oil polyoxyethylene ether and water, wherein the volume ratio of span80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, diethylene glycol, hydrogenated castor oil polyoxyethylene ether and water is 10-20:20-50:20-50:1000-2000.
Diethylene glycol is colorless, odorless, transparent, hygroscopic, viscous liquid, has spicy and sweet taste, is non-corrosive, and has low toxicity. Melting point: -6.5 ℃; boiling point: 245 ℃; freezing point: -10.45 ℃; relative density: 1.1161; refractive index: 1.4472; flash point: 123.9 ℃; is easy to dissolve in water, alcohol, acetone, diethyl ether, glycol and other polar solvents, and is insoluble in benzene and carbon tetrachloride. The chemical properties are similar to those of ethylene glycol. Can be directly used as a natural gas dehydration dryer, a textile lubricant, a softener, a solvent of nitrocellulose, resin, grease, printing ink and the like, can be used for preparing a cleaning agent, and can be used as a dispersive solvent in other daily chemicals such as the printing ink and the like. The diethylene glycol molecular structure contains two functional groups of ether bond and hydroxyl, so that the diethylene glycol has unique physical and chemical properties, therefore, the diethylene glycol can be used as raw material to prepare various chemical products such as ether, acid, ester, amine and the like, and the diethylene glycol can be widely applied to industries such as petrochemical industry, rubber, plastics, textiles, paint, adhesive, pharmacy and the like, and has very wide application. Diethylene glycol has low acute toxicity, and semi-lethal LD is taken orally by rats 50 >5000mg/kg. The diethylene glycol can be used as additive of agricultural chemical by utilizing the carrier property of diethylene glycol. A small amount of diglycol is added into some pesticides, which is helpful for the pesticides to permeate to the body surface so as to improve the drug effect.
Microemulsion is a clear transparent dispersion system composed of three substances of water phase, surfactant and oil phase, has better stability in thermodynamic aspect, has lower viscosity, and is transparent or semitransparent in appearance and isotropic. The microemulsion is thermodynamically stable because the surfactant and cosurfactant together function in the system. The particle size of the microemulsion is generally less than 100nm, and the microemulsion has better application in a plurality of fields. At present, the microemulsification technology is mainly applied to the fields of cosmetics, foods, pesticides, medicines and the like. Because of the problems of poor water solubility or poor oil solubility and poor stability of the substances with high content of bioactive components, the application of the substances in the development of pesticide systems is limited to a certain extent. The microemulsion provides a better channel for the utilization of the substances with high content of bioactive components, can be used as a functional component carrier, realizes the water solubility or oil solubility of the substances, and improves the dispersibility and bioavailability of the substances. At present, on the basis of researching the microemulsion, a more environment-friendly surfactant-free microemulsion is also developed, and the advantage is more obvious. According to the characteristics of diethylene glycol, a nano-microemulsion system is constructed: span80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, diethylene glycol, hydrogenated castor oil polyoxyethylene ether and water.
According to the invention, diethylene glycol is used as a main synergistic component, and microemulsion (span 80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, hydrogenated castor oil polyoxyethylene ether and water) with the function of a medicament is subjected to quantitative multi-step treatment, so that the preparation and application of the synergistic nano microemulsion of the sterilant are realized, and the preparation method is simple in procedure and easy to operate.
The second purpose of the invention is to provide a preparation method of the synergistic nano microemulsion of the mouse sterilant, which comprises the following steps:
(1) Uniformly mixing span80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, hydrogenated castor oil polyoxyethylene and diethylene glycol solution according to the formula amount;
(2) Adding water into the solution for dilution, wherein the water temperature is 60-80 ℃; stirring until the mixture is completely dissolved, and preparing the synergistic nano-microemulsion of the mouse sterilant.
The third object of the invention is to provide a murine bait material comprising the synergistic nano-microemulsion of the murine sterilant as an active ingredient.
The fourth object of the invention is to provide the application of the synergistic nano microemulsion of the mouse sterilant in preparing the mouse bait material.
Preferably, the method comprises the following steps:
(1) Adding the murine sterile agent into the synergistic nano-microemulsion of the murine sterile agent, and stirring until the mixture is uniform to form an sterile agent solution containing the synergistic nano-microemulsion of the murine sterile agent;
(2) Adding a bait material into the sterile agent solution containing the synergistic nano-microemulsion of the murine sterile agent in the step (1), uniformly stirring, airing or drying to obtain the murine bait material containing the synergistic nano-microemulsion of the murine sterile agent.
Preferably, the addition of the murine sterilant is that 5-20 g of the murine sterilant is added into every 1000mL of the synergistic nano microemulsion of the murine sterilant; the bait material is added into the synergistic nano-microemulsion of the mouse sterilant according to the proportion of 40-500 kg of the bait material in every 1000mL of the synergistic nano-microemulsion of the mouse sterilant.
Preferably, the murine sterilant is a lipid-soluble sterilant or a water-soluble sterilant.
Preferably, the murine sterilant is estramustine, chlordygestrel acetate or cabergoline.
Preferably, the bait material is selected from one or more of rice, wheat and corn.
The fifth object of the invention is to provide the application of the synergistic nano microemulsion of the mouse sterilant or the mouse bait material in inhibiting the reproduction of mice.
Compared with the prior art, the invention has the following advantages:
1. according to the invention, diethylene glycol is used as a main synergistic component, and microemulsion (span 80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, hydrogenated castor oil polyoxyethylene ether and water) with the function of a medicament is subjected to quantitative multi-step treatment, so that the preparation and application of the synergistic nano microemulsion are realized, and the preparation method is simple in procedure and easy to operate.
2. The invention fills the blank of the actual application field of the existing mouse sterilant synergistic nano microemulsion.
3. Reduces the dosage of the mouse sterilant by about 50 percent, saves the cost, reduces the environmental residue of the medicine and reduces the danger to other non-target organisms.
4. The bait material has high feeding index, obviously improves the prevention and control effects of the sterilant and reduces the reproduction rate of mice.
Detailed Description
The following examples are further illustrative of the invention and are not intended to be limiting thereof.
Unless specifically stated, the experimental materials and reagents in the present invention are all commercially available products conventional in the art.
Example 1:
measuring span8010 mL, 20mL of sodium dodecyl diphenyl ether disulfonate, 40mL of isomeric alcohol polyoxyethylene ether, 20mL of hydrogenated castor oil polyoxyethylene ether, 30mL of diethylene glycol, adding 1000mL of water at 80 ℃, and stirring and uniformly mixing to obtain a synergistic nano microemulsion solution of the sterilant; 400kg of fresh rice is weighed, 1000mL of prepared sterile agent synergistic nano-microemulsion solution is added, 400kg of bait material is added into each 1000mL of sterile agent synergistic nano-microemulsion solution, and the mixture is stirred uniformly and dried to prepare the synergistic medicinal bait.
Test adult Kunming mice (mice) were purchased from the medical laboratory animal center in Guangdong province. Single cage feeding (30 cm. Times.15 cm. Times.20 cm), with sawdust as a bedding, water and food (standard mouse feed, produced by Guangdong province medical laboratory animal center, SCXK (Guangdong) 2013-0002) were supplied adequately at room temperature 25+ -2deg.C and photoperiod 12L:12D (08:00-20:00). The test mice were acclimatized for more than 2 months for the experiment.
Healthy adult female and male mice are selected to be 16, and the mice are bred in a single cage, and the female and male mice are randomly divided into 2 groups (blank cereal bait group and synergistic cereal bait group), and 8 female and male mice in each group. The method comprises the steps of firstly feeding pure rice for one week, then respectively feeding 20g of blank cereal baits or synergistic cereal baits (namely synergistic medicinal baits) to two groups of mice each day, collecting the rest baits every 3 days, drying and weighing, and repeating the experiment for 9 days. Then, the male and female mice of the two groups are respectively put together for 7 days, and pure rice is fed during the period of putting together. Pregnancy and parity were recorded for each group of females. The reproduction of the female mice in the blank Gu Er and synergistic cereal bait groups is shown in Table 1:
TABLE 1
As can be seen from Table 1, the synergistic cereal baits alone did not affect the white mice reproduction, and the synergistic nanoemulsion solutions alone did not act.
Example 2:
measuring span8010 mL, 40mL of sodium dodecyl diphenyl ether disulfonate, 30mL of isomeric alcohol polyoxyethylene ether, 20mL of hydrogenated castor oil polyoxyethylene ether and 50mL of diethylene glycol, adding 1000mL of water at 70 ℃, and stirring and uniformly mixing to obtain a synergistic nano microemulsion solution of the sterilant; 1000mL of the mixed synergistic nano-microemulsion solution of the sterile agent is weighed, 20g of the ethinyl estradiol is added, 20g of the murine sterile agent is added into each 1000mL of the synergistic nano-microemulsion solution of the sterile agent, and the mixture is stirred until the mixture is completely dissolved, so that the sterile agent solution containing the synergistic nano-microemulsion of the sterile agent is obtained. 400kg of fresh rice is weighed, 1000mL of prepared sterile solution containing the sterile synergistic nano-emulsion is added, 400kg of bait material is added into each 1000mL of sterile solution containing the sterile synergistic nano-emulsion, and the mixture is stirred uniformly and dried to prepare the synergistic alkyne estramustine bait.
The common preparation method of the propargyl estrane bait solution is that 20g of propargyl estrane is added into 1000mL of water, and the mixture is stirred until the mixture is completely dissolved, thus obtaining the propargyl estrane solution. 400kg of fresh rice is weighed, 1000mL of the prepared propargyl estrane solution is added, 400kg of bait material is added into each 1000mL of the propargyl estrane solution, and the mixture is stirred uniformly and dried to prepare the common propargyl estrane bait.
Test adult Kunming mice (mice) were purchased from the medical laboratory animal center in Guangdong province. Adult black-edge rats were harvested from Feng Cun farm land in the city of great increase, guangdong province. Two kinds of mice were fed individually in a single cage (30 cm. Times.15 cm. Times.20 cm) with sawdust as a bedding, water and food (standard mouse feed, produced by Guangdong province medical laboratory animal center, SCXK (Guangdong) 2013-0002) were sufficiently supplied at room temperature 25.+ -. 2 ℃ and photoperiod 12L:12D (08: 00-20: 00). The test mice were acclimatized for more than 2 months for the experiment.
Healthy adult female and male mice are selected to be 24 mice each, and the mice are bred in a single cage, and the female/male mice are randomly divided into 3 groups (a blank cereal bait group, a synergistic alkyne-estramustine medicine bait group and a common alkyne-estramustine medicine bait group), and 8 mice in each group are bred. The animals were first kept on pure rice for one week, and thereafter, three groups of mice each had 20g of each of blank Gu Er, synergistic ethylestrone bait or ordinary ethylestrone bait, and the rest of the bait was collected every 3 days, dried and weighed, and the experiment was repeated three times for 9 days (feeding test of three kinds of bait by black-edge rats and Kunming mice), and feeding amounts of three kinds of bait [ (total feeding amount of bait-rest of bait)/(number of experimental days) ] of Kunming mice and black-edge rats were shown in Table 2.
Three groups of male and female mice are respectively put in cages for 7 days, and pure rice is freely taken during the cage putting period. Pregnancy and parity were recorded for each group of females. The propagation conditions of the blank cereal bait group, the synergistic alkyne-estramustine bait group and the common alkyne-estramustine bait group female mice are shown in table 3.
TABLE 2
TABLE 3 Table 3
As can be seen from table 2: the feeding amount of the synergistic propargyl estramur drug bait for the black-edge dentate mice and the white mice is obviously higher than that of the common propargyl estramur drug bait, and the diethylene glycol can improve the feeding amount of the synergistic propargyl estramur drug bait for the black-edge dentate mice and the white mice and increase the palatability of the propargyl estramur drug bait. As can be seen from the results in Table 3, the reproduction rate of mice fed with the synergistic propargyl estramustine bait was lower than that of the blank cereal bait group and the ordinary propargyl estramustine bait group, and only 30% of the control group and 50% of the ordinary propargyl estramustine bait group, and the number of reproduction offspring and the number of surviving offspring individuals were lower than those of the blank cereal bait group and the ordinary propargyl estramustine bait group. Showing that the diethylene glycol has synergistic effect on the sterile effect of the propargyl estrine.
Example 3:
measuring span8010 mL, 20mL of sodium dodecyl diphenyl ether disulfonate, 40mL of isomeric alcohol polyoxyethylene ether, 20mL of hydrogenated castor oil polyoxyethylene ether, 30mL of diethylene glycol, adding 1000mL of water at 80 ℃, and stirring and uniformly mixing to obtain a synergistic nano microemulsion solution of the sterilant; 1000mL of the sterile agent synergistic nano microemulsion solution after uniform mixing is weighed, 10g of chlordydrogesterone acetate is added, and 10g of chlordydrogesterone acetate is added into each 1000mL of the sterile agent synergistic nano microemulsion solution and stirred until the chlordydrogesterone acetate solution is completely dissolved, so that the synergistic chlordydrogesterone acetate solution is obtained. 400kg of fresh rice is weighed, 1000mL of prepared synergistic chlordydrogesterone acetate solution is added, 400kg of bait material is added into each 1000mL of synergistic chlordydrogesterone acetate solution, and the mixture is stirred uniformly and dried to prepare the synergistic chlordydrogesterone acetate bait.
The common chlordygesterone acetate bait solution is prepared by adding 10g of chlordygesterone acetate into 1000mL of water, and stirring until the chlordygesterone acetate is completely dissolved to obtain the chlordygesterone acetate solution. 400kg of fresh rice is weighed, 1000mL of prepared chlordygesterone acetate solution is added, 400kg of bait material is added into each 1000mL of chlordygesterone acetate solution, and the mixture is stirred uniformly and dried to prepare the common chlordygesterone acetate bait.
Test adult Kunming mice (mice) were purchased from the medical laboratory animal center in Guangdong province. Adult Huang Maoshu was collected from Feng Cun farmland in city-increasing city, guangdong province. Two kinds of mice were fed individually in a single cage (30 cm. Times.15 cm. Times.20 cm) with sawdust as a bedding, water and food (standard mouse feed, produced by Guangdong province medical laboratory animal center, SCXK (Guangdong) 2013-0002) were sufficiently supplied at room temperature 25.+ -. 2 ℃ and photoperiod 12L:12D (08: 00-20: 00). The test mice were acclimatized for more than 2 months for the experiment.
After 30 healthy adult female and male mice are selected and bred in a single cage for one week, the female/male mice are randomly divided into 3 groups (a blank cereal bait group, a synergistic chlordygesterone acetate drug bait group and a common chlordygesterone acetate drug bait group), and 10 female/male mice in each group are bred. Three groups of male and female mice are caged, and pure rice is fed during the cage-doubling period. After 7 days of cage closing, male and female mice are fed separately in a single cage, each of three groups of mice is respectively fed with 20g of blank Gu Er, synergistic chlordygesterone acetate drug bait or common chlordygesterone acetate drug bait every day, the rest of the bait is collected every 3 days, dried and weighed, the experiment is repeated for 9 days (Huang Maoshu feeding test of three baits is the same as that of a white mouse), and then pure rice is fed. Pregnancy and parity were recorded for each group of females.
The feeding amounts of the mice and Huang Maoshu for the three baits are shown in table 4. The propagation conditions of the blank cereal bait group, the synergistic chlordygesterone acetate drug bait group and the female mice of the common chlordygesterone acetate drug bait group are shown in table 5.
TABLE 4 Table 4
TABLE 5
As can be seen from table 4: huang Maoshu and mice have a higher feed intake for the synergistic chlordygesterone acetate bait than for the conventional chlordygesterone acetate bait, and diethylene glycol can improve the palatability of the chlordygesterone acetate. As can be seen from the results of table 5, the reproduction rate of mice fed with the chlordygesterone acetate bait was lower than that of the blank Gu Er group, the reproduction rate of the synergistic chlordygesterone acetate bait group was only 30% of that of the control group, and was 50% of that of the conventional chlordygesterone acetate bait group, and the number of reproduction offspring and the number of individuals of the survival offspring of the synergistic chlordygesterone acetate bait group were lower than those of the blank cereal bait group and the conventional chlordygesterone acetate bait group. Showing that the diglycol has a synergistic effect on the sterile effect of the chlordydrogesterone acetate.
Example 4:
measuring span8020 mL, 50mL of sodium dodecyl diphenyl ether disulfonate, 50mL of isomeric alcohol polyoxyethylene ether, 50mL of hydrogenated castor oil polyoxyethylene ether and 50mL of diethylene glycol, adding 2000mL of water at 60 ℃, and stirring and mixing uniformly to obtain a synergistic nano microemulsion solution of the sterilant; 2000mL of the mixed sterile agent synergistic nano microemulsion solution is weighed, 5g of cabergoline is added, and 5g of cabergoline is added into each 2000mL of sterile agent synergistic nano microemulsion solution, and the mixture is stirred until the solution is completely dissolved, thus obtaining the synergistic cabergoline solution. Weighing 500kg of fresh wheat, adding 2000mL of prepared synergistic cabergoline solution, adding 500kg of bait material into each 2000mL of synergistic cabergoline solution, stirring uniformly, and airing to obtain the synergistic cabergoline bait.
The common preparation method of the cabergoline bait solution is that 5g of cabergoline is added into 2000mL of water and stirred until the cabergoline is completely dissolved, thus obtaining the cabergoline solution. Weighing 500kg of fresh wheat, adding 2000mL of prepared cabergoline solution, adding 500kg of bait material into each 2000mL of cabergoline solution, stirring uniformly, and airing to obtain the common cabergoline bait.
Test adult Kunming mice (mice) were purchased from the medical laboratory animal center in Guangdong province. Single cage feeding (30 cm. Times.15 cm. Times.20 cm), with sawdust as a bedding, water and food (standard mouse feed, produced by Guangdong province medical laboratory animal center, SCXK (Guangdong) 2013-0002) were supplied adequately at room temperature 25+ -2deg.C and photoperiod 12L:12D (08:00-20:00). The test mice were acclimatized for more than 2 months for the experiment.
30 healthy adult female and male mice are selected, and the female/male mice are randomly divided into 3 groups (blank wheat-based bait group, synergistic cabergoline drug-bait group and common cabergoline drug-bait group), and 10 female/male mice in each group. Three groups of male and female mice are put together, pure rice is firstly fed during the cage combination period, after the cage combination period is 7 days, the male and female mice are separately fed in a single cage, and then each of the three groups of mice is respectively fed with 20g of blank wheat-based bait, synergistic cabergoline medicinal bait or common cabergoline medicinal bait every day, and the experiment is repeated three times for 9 days. And then normal feed feeding. Pregnancy and parity were recorded for each group of females. The reproduction of female mice in the blank wheat-based bait group, the synergistic cabergoline bait group and the ordinary cabergoline bait group is shown in Table 6.
TABLE 6
As can be seen from the results in Table 6, the reproduction rate of mice fed with the synergistic cabergoline bait is lower than that of the blank group and the common cabergoline bait group, and the reproduction rate of female mice is only 30% of that of the blank group and 60% of that of the common cabergoline bait group. The number of the reproduction offspring and the number of the survival offspring of the synergistic cabergoline medicine bait group are lower than those of the blank wheat-based bait group and the common cabergoline medicine bait group. Showing that diethylene glycol has a synergistic effect on the sterility effect of cabergoline.
Example 5:
measuring span8010 mL, 20mL of sodium dodecyl diphenyl ether disulfonate, 20mL of isomeric alcohol polyoxyethylene ether, 20mL of hydrogenated castor oil polyoxyethylene ether, 50mL of diethylene glycol, adding 1000mL of water at 80 ℃, and stirring and uniformly mixing to obtain a synergistic nano microemulsion solution of the sterilant; 1000mL of the mixed synergistic nano-microemulsion solution of the sterile agent is weighed, 20g of the ethinyl estradiol is added, 20g of the murine sterile agent is added into each 1000mL of the synergistic nano-microemulsion solution of the sterile agent, and the mixture is stirred until the mixture is completely dissolved, so that the sterile agent solution containing the synergistic nano-microemulsion of the sterile agent is obtained. Weighing 40kg of fresh rice, adding 1000mL of prepared sterile solution containing the sterile synergistic nano-emulsion, adding 40kg of bait material into each 1000mL of sterile solution containing the sterile synergistic nano-emulsion, stirring uniformly, and airing to obtain the synergistic alkyne estramustine bait.
The common preparation method of the propargyl estrane bait solution is that 20g of propargyl estrane is added into 1000mL of water, and the mixture is stirred until the mixture is completely dissolved, thus obtaining the propargyl estrane solution. Weighing 40kg of fresh rice, adding 1000mL of the prepared propargyl estrane solution, adding 40kg of bait material into each 1000mL of the propargyl estrane solution, stirring uniformly, and airing to obtain the common propargyl estrane bait.
Determination of the content of the propargyl estrane in the rice: laboratory instrument and reagent: agilent 1260 high performance liquid chromatograph, variable wavelength uv detector; the reference product (China food and drug inspection institute, batch number: 100048-201503 for content determination, according to C) 25 H 32 O 2 Content 98.6%); methanol and absolute ethanol are chromatographic pure, and other reagents are analytically pure. Chromatographic column: agilent C18 (250 mm. Times.4.6 mm, 5)μm); mobile phase: methanol-water (90:10); flow rate: 1.0mL/min; detection wavelength: 279nm; sample injection amount: 20. Mu.L; column temperature: 30 ℃.
The standard product of the propargyl estrane is weighed, and methanol solution is used for preparing standard working solution of the propargyl estrane with the concentration of 10, 20, 30, 40, 50 and 60 mug/mL. And respectively sucking 10, 20, 30, 40, 50 and 60 mu g/mL of standard working solution of the propargyl estrus ether, analyzing 20 mu L of sample injection, drawing a standard curve by taking the sample injection amount of the standard substance as an abscissa X and the chromatographic peak area as an ordinate Y, and obtaining a regression equation: y= 5.612X-3.02 (R 2 =0.9999). Weighing 10g of common and synergistic propargyl estrane baits 3 parts each, separating the baits (rice) into brown rice (pulverized brown rice) and rice husk, repeatedly dissolving with methanol solution, passing through 0.22 μm microporous filter membrane, and measuring (recovering rate)>90%). The content of the propargyl estramur acid in the brown rice and the rice husk of the common propargyl estramur acid bait and the synergistic propargyl estramur acid bait were calculated respectively (see Table 7).
TABLE 7
As can be seen from the results in Table 7, the rice husk content in the conventional propargyl-estramustine bait accounts for 91.7% of the total dosage, and the brown rice content accounts for 8.3% of the total dosage; the rice hull content of the synergistic propargyl-estrant bait accounts for 83.3 percent of the total dosage, and the brown rice content accounts for 16.7 percent of the total dosage. The synergistic nano microemulsion of the sterilant can rapidly and effectively dissolve the propargyl estrap, and remarkably improve the content of the propargyl estrap in the brown rice to 2 times of that of a control group.
The above embodiments are only described to assist in understanding the technical solution of the present invention and its core idea, and it should be noted that it will be obvious to those skilled in the art that several improvements and modifications can be made to the present invention without departing from the principle of the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.
Claims (10)
1. The synergistic nano microemulsion of the mouse sterilant is characterized by comprising span80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, diethylene glycol, hydrogenated castor oil polyoxyethylene ether and water, wherein the volume ratio of span80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, diethylene glycol, hydrogenated castor oil polyoxyethylene ether and water is 10-20:20-50:20-50:1000-2000.
2. A method for preparing the synergistic nano microemulsion of the mouse sterilant according to claim 1, which comprises the following steps:
(1) Uniformly mixing span80, sodium dodecyl diphenyl ether disulfonate, isomeric alcohol polyoxyethylene ether, hydrogenated castor oil polyoxyethylene and diethylene glycol solution according to the formula amount;
(2) Adding water into the solution for dilution, wherein the water temperature is 60-80 ℃; stirring until the mixture is completely dissolved, and preparing the synergistic nano-microemulsion of the mouse sterilant.
3. A murine bait material characterized by: comprising the synergistic nanoemulsion of claim 1 as active ingredient.
4. Use of the synergistic nanoemulsion of claim 1 for the preparation of a murine bait material.
5. The use according to claim 4, characterized in that it comprises the following steps:
(1) Adding the murine sterile agent into the synergistic nano-microemulsion of the murine sterile agent, and stirring until the mixture is uniform to form an sterile agent solution containing the synergistic nano-microemulsion of the murine sterile agent;
(2) Adding a bait material into the sterile agent solution containing the synergistic nano-microemulsion of the murine sterile agent in the step (1), uniformly stirring, airing or drying to obtain the murine bait material containing the synergistic nano-microemulsion of the murine sterile agent.
6. The use according to claim 5, wherein the addition of the murine sterilant is 5-20 g of the murine sterilant per 1000mL of the synergistic nanoemulsion; the bait material is added into the synergistic nano-microemulsion of the mouse sterilant according to the proportion of 40-500 kg of the bait material in every 1000mL of the synergistic nano-microemulsion of the mouse sterilant.
7. The use according to claim 4, 5 or 6, wherein the murine sterilant is a lipid-soluble sterilant or a water-soluble sterilant.
8. The use according to claim 4, 5 or 6, wherein the murine sterilant is ethinyl estrone, chlordygestrel acetate or cabergoline.
9. The use according to claim 4, 5 or 6, wherein the bait material is selected from more than one of rice, wheat and maize.
10. Use of the synergistic nanoemulsion of a murine sterilant according to claim 1 or the murine bait material according to claim 3 for inhibiting the proliferation of mice.
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