CN103385867B - Application of sesquiterpenoids in preparing mite killing medicine - Google Patents
Application of sesquiterpenoids in preparing mite killing medicine Download PDFInfo
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Abstract
The invention relates to the field of medicinal chemistry, and discloses an application of sesquiterpenoids in preparing a mite killing medicine and a mite killing medicine comprising the sesquiterpenoids. According to the application of sesquiterpenoids in preparing a mite killing medicine, disclosed by the invention, the structure of the adopted sesquiterpenoids is shown by the formula I. When applied to mite killing, the sesquiterpenoids have an obvious mite killing effect and realize a killing effect on animal mites; the sesquiterpenoids belong to natural plant-source mite killing medicines, and have the characteristics that drug resistance is avoided, the sesquiterpenoids can be self-degraded in the environment, are not left in an animal product or enriched through a food chain and are relatively safe to human bodies, animals and the environment and the like; and the sesquiterpenoids can be used for preparing a mite killing medicine.
Description
Technical field
The present invention relates to field of pharmaceutical chemistry technology, particularly relate to a kind of sesquiterpenoids and preparing the application in miticide.
Background technology
Demodicid mite (Acarid) belongs to invertebrates, Arthropoda, Arachnoidea, the animal of demodicid mite subclass, and most demodicid mite bodily form is soft, very little, and naked eyes just can be seen, are generally 0.1 millimeter to several millimeters.The kind of current known demodicid mite about 50,000 kinds, colonizes in underground, on the ground, in high mountain, water and on people or organism, infects various diseases or harm the crops.Animal acaricide is Sarcoptidae, the mites infest of itch mite section and Demodicidae causes in animal skin a kind of contact, infectiousness, refractory skin, with the violent pruritus of infected animal and serious scytitis for feature.Animal acaricide spreads in all over the world, is commonly called as " scabies " at folks of china, generally betides the many animals of each age level, domestic animal all PIs such as cattle, sheep, rabbit, pig, Canis familiaris L., very large to animal farming industry harm.
At present, for the control of animal acaricide, generally use chemical synthetic drug, such as, Amitraz, basudin, fenvalerate, ivermectin and doractin etc.These chemical synthetic drugs have been proved the acaricide effectively can preventing and treating animal, but long-term a large amount of this type of Chemical acaricide that uses brings a series of problem, as serious drug residue, environmental hazard, drug resistance etc.Therefore, the alternative medicine of effective, the low toxicity of exploitation, noresidue just becomes the task of top priority.Compared with chemical classes miticide, plant-derived acaricide also shows great Development volue in the control of parazoon, and its therapeutic effect is not second to any efficient pest control with insecticide medicine.Meanwhile, plant-derived miticide also has and not easily produces drug resistance, can degrade voluntarily in the environment, residual or by food chain enrichment in livestock products, to people and animals and the feature such as environment is comparatively safe.Therefore, find efficient, safe plant-derived miticide and have very important meaning to the sustainable development and human and livestock health of safeguarding ecological environment.
Sesquiterpenoid refers to the natural terpenoids containing 15 carbon atoms in molecule, and distributed more widely at occurring in nature, being often present in volatile oil with alcohol, ketone, lactone etc. form in plant, is the key component of high-boiling fration in volatile oil.Sesquiterpenoids has stronger fragrance and biological activity more, is the important source material of medicine, food, cosmetics industry, is also one of important plant-derived medicament sources.Structure is such as formula the sesquiterpenoids shown in I, and 9 β-hydroxy-ageraphorone (9 beta-hydroxy Herba Lycopi ketone) are a kind of monomeric compounds that extraction and isolation obtains from Eupatorium cannabinum L. (Eupatorium coelestinum L.),
At present, there is no the report about this compound with acaricidal activity.
Summary of the invention
In view of this, the object of the present invention is to provide a kind of sesquiterpenoids preparing the application in miticide, this compound belongs to plant-derived medicine, has significant miticidal effect, has killing action to animal demodicid mite, can be applied to and prepare miticide.
In order to realize object of the present invention, the present invention adopts following technical scheme:
The invention provides a kind of structure and prepare the application in miticide such as formula the sesquiterpenoids shown in I,
Preferably, above-mentioned application for demodicid mite be animal demodicid mite.
At embodiments of the invention, demodicid mite used in application provided by the present invention is itch mite.
Preferably, the miticide in application provided by the present invention, in g/mL, structure is 0.25% ~ 0.5% such as formula the mass body volume concentrations of the sesquiterpenoids shown in I,
In certain embodiments of the present invention, structure used in application provided by the present invention is through the monomeric compound that extraction and isolation obtains from Eupatorium cannabinum L. (Eupatorium coelestinum L.) such as formula the sesquiterpenoids shown in I,
Concrete extraction separation method is:
The acquisition of Eupatorium cannabinum L. (Eupatorium coelestinum L.) petroleum ether extract: Eupatorium cannabinum L. (Eupatorium coelestinum L.) herb dry powder extracts through alcohol heat reflux, petroleum ether extraction, obtains Eupatorium cannabinum L. (Eupatorium coelestinum L.) petroleum ether extract;
Mix sample: get Eupatorium cannabinum L. (Eupatorium coelestinum L.) petroleum ether extract, with acetone solution, gained solution is mixed with column chromatography silica gel, the silica gel of petroleum ether extract must have been adsorbed;
Dress post: take column chromatography silica gel, mix thoroughly with petroleum ether, after draining bubble, pour in glass chromatography column;
Loading: will the silica gel having adsorbed petroleum ether extract of gained in sample step be mixed be added to the upper strata of the chromatographic column of gained in dress post step;
Eluting: using the mixed solution of petroleum ether/acetone as eluant, carries out gradient elution, obtains eluting gleanings;
Detect: the eluting gleanings of gained carried out detect, analyze, merge and obtain a component;
By obtained component, repeat above-mentioned to mix sample, dress post, loading, eluting and detecting step 3 times, separation, purification, obtain monomeric compound.
Present invention also offers a kind of miticide, it comprises structure such as formula the sesquiterpenoids shown in I and pharmaceutically acceptable adjuvant,
Preferably, in g/mL, in miticide provided by the present invention, structure is 0.25% ~ 0.5% such as formula the mass body volume concentrations of the sesquiterpenoids shown in I,
Preferably, miticide provided by the present invention for demodicid mite be animal demodicid mite.
More preferably, miticide provided by the present invention for demodicid mite be itch mite.
Preferably, the dosage form of miticide provided by the invention is emulsifiable concentrate, suspending agent, powder, granule or ointment.
The invention provides a kind of sesquiterpenoids at the application prepared in miticide and a kind of miticide containing this sesquiterpenoids, the structure of this sesquiterpenoids is such as formula shown in I.Experimental data shows, this sesquiterpenoids is killing the application in demodicid mite, compared with positive control, this compound has significant miticidal effect, to animal demodicid mite, there is killing action, and this compound belongs to natural plant miticide, have not easily produce drug resistance, can degrade voluntarily in the environment, residual in livestock products or by food chain enrichment, to people and animals and the feature such as environment is comparatively safe, can be applied to and prepare miticide
Accompanying drawing explanation
Fig. 1 shows proton nmr spectra (1H-NMR) spectrogram of the compound of the embodiment of the present invention 1 gained;
Fig. 2 shows carbon-13 nmr spectra (13C-NMR) spectrogram of the compound of the embodiment of the present invention 1 gained.
Detailed description of the invention
The invention discloses a kind of sesquiterpenoids and prepare the application in miticide.Those skilled in the art can realize its application with reference to present disclosure, and special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, they are all deemed to be included in the present invention.Methods and applications of the present invention are described by preferred embodiment, related personnel obviously can change methods and applications herein or suitably changes and combination not departing from content of the present invention, spirit and scope, realizes and applies the technology of the present invention.
A kind of sesquiterpenoids provided by the invention to prepare in the application in miticide used reagent and raw material all can be buied by market.
In order to enable those skilled in the art understand technical scheme of the present invention better, below in conjunction with embodiment, set forth the present invention further:
The acquisition of embodiment 1 sesquiterpenoids
The acquisition of Eupatorium cannabinum L. (Eupatorium coelestinum L.) petroleum ether extract: the Eupatorium cannabinum L. (Eupatorium coelestinum L.) being collected in Xichang City, Sichuan Province is dried rear pulverizing naturally and obtains Eupatorium cannabinum L. (Eupatorium coelestinum L.) herb dry powder.Get 8kg Eupatorium cannabinum L. (Eupatorium coelestinum L.) herb dry powder, extract three times with 8-10 95% alcohol heat reflux doubly respectively several times, then namely merge extractive liquid, concentrating under reduced pressure obtains Eupatorium cannabinum L. (Eupatorium coelestinum L.) ethanol extraction.The Eupatorium cannabinum L. (Eupatorium coelestinum L.) ethanol extraction of gained is scattered in 4L water, with 4L petroleum ether extraction three times, is separated, obtains petroleum ether extract.
Mix sample: the petroleum ether extract 48g getting gained, adds proper amount of acetone and dissolve to it.Taking 98g200-300 object column chromatography silica gel is put in evaporating dish, and evaporating dish is put on the water-bath of 60 DEG C, then the acetone soln being dissolved with petroleum ether extract is added on the silica gel in evaporating dish gradually, continue to add until completely after acetone volatilization, make petroleum ether extract all by silica gel adsorption, the silica gel of petroleum ether extract must have been adsorbed.
Dress post: take 1000g200-300 object column chromatography silica gel, mix thoroughly with 2000mL petroleum ether, after draining bubble, pour in glass chromatography column, strike real silicagel column to improve its separating effect.
Loading: will the silica gel having adsorbed petroleum ether extract of gained in sample step be mixed be added to the upper strata of the silicagel column of gained in dress post step.
Eluting: with the mixed solution of petroleum ether/acetone for eluting solvent.With volume basis, the solution concentration gradient of petroleum ether/acetone is: petroleum ether: acetone is respectively 50:1,40:1,30:1,20:1,10:1,5:1, each gradient volume is 50000mL, carry out eluting, about 500mL receives one bottle, then under 60 DEG C of conditions, carries out concentrating under reduced pressure, obtains eluting gleanings.
Detect: gained eluting gleanings tlc silica gel is analyzed, with petroleum ether/acetone, volume ratio be 7:1 as developing solvent, carry out expansion eluting.By observing ultraviolet and sulphuric acid-ethanol spraying heating colour developing result, merging proximate composition, obtaining a component.
By obtained component, repeat above-mentioned to mix sample, dress post, loading, eluting and detecting step 3 times, separation, purification, obtain monomeric compound.
Structural Identification: utilize proton nmr spectra (
1h-NMR) in conjunction with carbon-13 nmr spectra (
13c-NMR) method carries out Structural Identification to the monomeric compound obtained.
1h-NMR and
13c-NMR is all with CDCl
3(deuterochloroform) is solvent, TMS (tetramethylsilane) is interior mark, above Spectrum Analysis measured by West China Institute of Analysis of Sichuan University and Chinese Academy of Sciences's Chengdu biology, and used nuclear magnetic resonance analyser is BRUKERDRX-500 type nuclear magnetic resonance analyser.
Experimental result finds, this material is colorless oil, sends strong darkviolet fluorescence under irradiation under ultraviolet ray, indicates that this compound has conjugated system structure.The proton nmr spectra of this material (
1h-NMR) as shown in Figure 1, its carbon-13 nmr spectra (
13c-NMR) as shown in Figure 2.Proton nmr spectra (
1h-NMR), namely in Fig. 1, δ
h6.79 proton signals show this compound and contain an alkene hydrogen, δ
h1.70,3 H, approximate unimodal, show this compound and there is the methyl that has remote couplings, δ
h0.84,0.95,1.00, each 3 H, bimodal, show this compound and there are three split and be divided into bimodal methyl.Its carbon-13 nmr spectra (
13c-NMR), i.e. Fig. 2, shows 15 carbon signals, indicates that this compound may contain 15 carbon.Wherein δ
cthe carbon signal of 199.6, showing this compound has a ketone carbonyl; δ
ctwo carbon signals of 146.7,132.9, showing this compound has a double bond, δ
c66.9 these compounds of indication have the carbon be connected with hydroxyl.Embodiment 1 gained monomeric compound
1h NMR compose and
13the chemical displacement value that C NMR composes is in table 1, and comprehensive proton nmr spectra and carbon spectrum information, can infer that this compound is sesquiterpenoids.
Table 1 embodiment 1 gained monomeric compound
1h NMR compose and
13chemical displacement value/ppm that C NMR composes
Resolve the signal of its hydrogen nuclear magnetic resonance and the signal of nuclear magnetic resonance, NMR carbon, find that the chemical shift of the hydrogen of the 9 β-hydroxy-ageraphorone (9 beta-hydroxy Herba Lycopi ketone) reported in the A new sequiterpenoid from Eupatorium adenophorum Spreng that (2006) such as Six cadinene derivatives fromageratina adenophora and He Lan that this compound and Bohlmann (1981) deliver on phytochemistry periodical deliver on Chinese Journal of Chemistry periodical is basically identical, therefore this compound identification is for structure is such as formula the sesquiterpenoids shown in I, i.e. 9 β-hydroxy-ageraphorone (9 beta-hydroxy Herba Lycopi ketone), its molecular formula is C
15h
24o
2,
The in vitro insecticidal activity assay of embodiment 2 sesquiterpenoids
Be separated in the new zealand rabbit auditory meatus of severe infections psoroptes cuniculi and collect crust, be placed in glass dish, and plate is positioned in 35 DEG C of incubators and cultivates 0.5h-1h, after climbing out of from crust in the incubator of itch mite at higher temperature, the energetic itch mite that picking climbs out of is tested.
Structure embodiment 1 obtained, such as formula the sesquiterpenoids shown in I, carries out in vitro insecticidal activity assay,
Experimental group, blank group and positive controls are established in experiment.Wherein, experimental group agents useful for same is the sesquiterpenoids solution of embodiment 1 gained of variable concentrations, in g/mL, in experimental group agents useful for same, structure is respectively 0.5%, 0.25%, 0.125%, 0.06% such as formula the mass body volume concentrations of the sesquiterpenoids shown in I, and solvent is volume is the glycerol of 1:1 and the mixed liquor of distilled water; Blank group agents useful for same is volume basis is the glycerol of 1:1 and the mixed liquor of distilled water; Positive controls agents useful for same is fenvalerate medicinal liquid, and corresponding concentration is 600mg/L, and namely in g/mL, its mass body volume concentrations is 0.06%.Concrete operations are: respectively get the experimental group solution of 1mL variable concentrations, placebo solution and positive control medicinal liquid and be added drop-wise to respectively on the Tissue Culture Plate of the Costar3516 in 6 different holes, and labelling one by one; On the Tissue Culture Plate of gained, each placement 2 Xinhua's filter paper, make often to open filter paper and soak a kind of solution, and one_to_one corresponding labelling; Often to open on the filter paper soaked the itch mite of evenly placing and providing in 10 the present embodiment, filter paper being placed in relative humidity is 75%, and temperature is cultivate in the incubator of 25 DEG C, each group respectively arrange 3 parallel.Regular check, uses needle stimulus acarid, determines whether death.
Adopt average mortality and median lethal time (LT
50) evaluate the in vitro virulence effect of this compound to demodicid mite.Adopt formula: average mortality/%=Mean Death number/20 × 100, average mortality corresponding under calculating this compound variable concentrations, different time.The data acquisition SAS software of gained is carried out statistical analysis, variance analysis is carried out to the miticidal effect of this compound, investigate the miticidal effect of variable concentrations.Application probability value regression model draws the in vitro toxicity regression curve of this compound, calculates median lethal time LT
50.
Embodiment 1 obtain compound and comparative example to the average mortality corresponding to groups different in the in vitro virulence effect of itch mite in table 2.
The compound that table 2 embodiment 1 obtains and comparative example are to the in vitro virulence effect of itch mite
* note: different capitalization of going together represents significant difference (P<0.05), in same column bracket, different capitalization represents significant difference (P<0.05).
Can find from table 2, under the identical time, along with the increase of this compound concentration, insecticidal effect increases gradually; Under identical concentration, along with the prolongation of compound effects time, insecticidal effect increases gradually; Compared with positive control fenvalerate, find, this compound is 0.25% in its concentration, after action time 4h, creates certain kill activity to itch mite; When the concentration of this compound reaches 0.5%, the miticidal effect of this compound is better than the miticidal effect of fenvalerate.
Adopt SAS software, in vitro toxicity regression curve to itch mite under good 0.25% concentration of this compound effects effect and 0.5% concentration in the present embodiment that application probability value regression model draws, median lethal time (LT corresponding under calculating this compound 0.25% concentration and 0.5% concentration
50).In vitro virulence (LT to itch mite under compound 0.25% concentration that the embodiment 1 that obtains according to this model obtains and 0.5% concentration
50) regression analysis of probability value is in table 3.
The compound that table 3 embodiment 1 obtains is to the in vitro virulence (LT of itch mite
50) regression analysis of probability value
From table 3, can find out, under 0.25%, 0.5% concentration, this compound is in the in vitro leaching virus killing power of itch mite, median lethal time (LT
50) be respectively 18.138h and 7.665h.Can obtain, this compound has certain killing action to itch mite, can be applied to and prepare miticide.
Experimental result shows, this compound has certain miticidal effect, has killing action to animal demodicid mite, can be applied to and prepare miticide.
Embodiment 3 sesquiterpenoids is to the clinical treatment of psoroptes cuniculi disease
In order to verify that structure is such as formula the clinical therapeutic efficacy of the sesquiterpenoids shown in I to animal acaricide further, the structure that Example 1 obtains, such as formula the sesquiterpenoids shown in I, is applied to the treatment to psoroptes cuniculi acaricide,
The new zealand rabbit of random choose 30 infected rabbits itch mites from the warren of breaking out psoroptes cuniculi disease, selected for examination new zealand rabbit age, body weight quite the gradient of infection of left ear and auris dextra is close, does not use other miticide to treat when breaking out psoroptes cuniculi disease.Meanwhile, that selects is good for examination new zealand rabbit Immunity, without infecting Other diseases situation.By selected 30 rabbits, be divided into 5 groups at random, often organize 6, be labeled as A group, B group, C group, D group, E group respectively, for examination.Meanwhile, kill the effect of parasitic psoroptes cuniculi in order to evaluation structure immerses crust such as formula the sesquiterpenoids shown in I, 30 for the new zealand rabbit tried all pincet take crusts all in left auditory meatus away, and the crust in right ear canal all retains.Setup Experiments experimental group 1, experimental group 2, experimental group 3, blank group, positive controls.Wherein, experimental group 1 is: in g/mL, and the mass body volume concentrations of the sesquiterpenoids of embodiment 1 gained is the solution of 0.25%, and namely its concentration is 0.25%, and solvent is volume ratio is the glycerol of 1:1 and the mixed solution of water, is applied to A group for examination rabbit; Experimental group 2 is: in g/mL, and the mass body volume concentrations of the sesquiterpenoids of embodiment 1 gained is the solution of 0.40%, and namely its concentration is 0.40%, and solvent is volume ratio is the glycerol of 1:1 and the mixed solution of water, is applied to B group for examination rabbit; Experimental group 3 is: in g/mL, and the mass body volume concentrations of the sesquiterpenoids of embodiment 1 gained is the solution of 0.50%, and namely its concentration is 0.50%, and solvent is volume ratio is the glycerol of 1:1 and the mixed solution of water, is applied to C group for examination rabbit; Positive control is buy the ivermectin in universe animal pharmaceutical estate company, by recommended amounts, and every 1kg body weight 0.2mg medicine, i.e. 0.2mg/kg, uses, and is applied to D group for examination rabbit; Blank group is volume ratio is the glycerol of 1:1 and the mixed solution of water, is applied to E group for examination rabbit.Experimental group 1, experimental group 2 and experimental group 3 adopt the mode administration of embrocating, and positive control adopts the mode administration of injection, and blank adopts the mode administration of embrocating.All animals all carry out two treatments, after the treatment of dispenser first, within the 7th day, again carry out the 2nd medication treatment.Check the clinical manifestation after for the medication of examination new zealand rabbit every day, recording exceptional response situation.Within every 7 days, carry out a detailed inspection, whether the scope of examination comprises with still having itch mite parasitic in the left and right auditory meatus of otoscopy, passes judgment on and records clinical-grade and photograph etc., and the part crust in random collecting every ear, for test therapeutic effect.
Adopt to infect and recover to mark with treatment and therapeutic effect evaluates the clinical therapeutic efficacy of this experiment.Wherein, psoroptes cuniculi disease infects and recovers standards of grading in table 4 with treatment.
The sick clinical symptoms of table 4 psoroptes cuniculi describes grading system with recovery
| Infect the description with recovery extent | Grading system |
| There is no crust and/or acarid | 0 |
| Auditory meatus has stimulation, but does not have acarid | 0.5 |
| Crust in a small amount, a small amount of acarid | 1 |
| External auditory meatus has crust, has acarid | 2 |
| Auditory meatus near-end 1/4 is full of crust, has acarid | 3 |
| Auditory meatus near-end 1/2 is full of crust, has acarid | 4 |
| Auditory meatus near-end 3/4 is full of crust, has acarid | 5 |
| All external auditory meatus is full of crust, has acarid | 6 |
Adopt formula:
Calculate the therapeutic effect of each group.The crust that takes out before collecting treatment and in treatment, labelling one by one collected also by the crust of an every new zealand rabbit plate that is clean, the wide 2cm of long 10cm.Smash crust to pieces with taking the photograph son and crust in small, broken bits is mixed, random picking 0.5g-1g crust, correct amount is placed in another clean little plate, and correspondence labelling one by one, little plate is positioned in 35 DEG C of incubators and cultivates 0.5h-1h, collect acarid and accurately calculate mite population.Then, according to the therapeutic effect of each treatment group of above-mentioned formulae discovery.
Data statistics adopts SAS software to analyze, and whether inspection therapeutic outcome is remarkable with the difference infected and treatment recovers to mark, and carries out multiple comparisons to the clinical treatment outcome that 5 are organized simultaneously.Scoring statistical result after recovering for the left ear ear infections of examination rabbit and treatment is in table 5, the scoring statistical result after recovering with treatment is infected in table 6 for examination rabbit right ear canal, therapeutic effect after recovering for the left ear ear infections of examination rabbit and treatment, in table 7, infects the therapeutic effect after recovering with treatment in table 8 for examination rabbit right ear canal.
Scoring statistical result (average mark ± SE) after table 5 recovers for the left ear ear infections of examination rabbit and treatment
| Treatment natural law | A group | B group | C group | D group | E group |
| 0 | 3.34±0.34Aa | 3.28±0.25Aa | 3.25±0.12Aa | 3.06±0.35Aa | 3.30±0.14Aa |
| 7 | 0.47±0.02Bb | 0.42±0.16Bb | 0.36±0.02Bb | 0.38±0.05Bb | 2.70±0.23Aa |
| 14 | 0.00±0.00Bb | 0.00±0.00Bb | 0.00±0.00Bb | 0.00±0.00Bb | 2.90±0.04Aa |
| 30 | 0.00±0.00Bb | 0.00±0.00Bb | 0.00±0.00Bb | 0.00±0.00Bb | 3.16±0.11Aa |
* note: different capitalization of going together represents that difference extremely significantly (P<0.01), and different lowercase alphabet shows significant difference (P<0.05)
Table 6 infects the scoring statistical result (average mark ± SE) after recovering with treatment for examination rabbit right ear canal
| Treatment natural law | A group | B group | C group | D group | E group |
| 0 | 3.72±0.31Aa | 3.54±0.28Aa | 3.48±0.16Aa | 3.56±0.20Aa | 3.45±0.18Aa |
| 7 | 0.45±0.04Bb | 0.38±0.06Bb | 0.32±0.12Bb | 0.45±0.02Bb | 3.28±0.11Aa |
| 14 | 0.00±0.00Bb | 0.00±0.00Bb | 0.00±0.00Bb | 0.00±0.00Bb | 3.32±0.16Aa |
| 30 | 0.00±0.00Bb | 0.00±0.00Bb | 0.00±0.00Bb | 0.00±0.00Bb | 3.67±0.11Aa |
* note: different capitalization of going together represents that difference extremely significantly (P<0.01), and different lowercase alphabet shows significant difference (P<0.05)
Therapeutic effect after table 7 recovers for the left ear ear infections of examination rabbit and treatment
| Treatment natural law | A group | B group | C group | D group | E group |
| 0 | 0 | 0 | 0 | 0 | 0 |
| 7 | 100.00% | 100.00% | 100.00% | 100.00% | 8.15% |
| 14 | 100.00% | 100.00% | 100.00% | 100.00% | 2.06% |
| 30 | 100.00% | 100.00% | 100.00% | 100.00% | 1.07% |
Table 8 infects the therapeutic effect after recovering with treatment for examination rabbit right ear canal
| Treatment natural law | A group | B group | C group | D group | E group |
| 0 | 0 | 0 | 0 | 0 | 0 |
| 7 | 100.00% | 100.00% | 100.00% | 100.00% | 3.53% |
| 14 | 100.00% | 100.00% | 100.00% | 100.00% | 0 |
| 30 | 100.00% | 100.00% | 100.00% | 100.00% | 0 |
Before the treatment respectively to infecting checking for examination new zealand rabbit auditory meatus of itch mite, the infection conditions for examination new zealand rabbit is respectively organized according to the standards of grading record of table 4, add up each experimental group and infect the meansigma methods recovering with treatment to mark, the results are shown in Table 5, table 6, as can be seen from result, before treatment, each group gradient of infection is close, and difference is not remarkable.Within after medication the 7th day first, check and find, A group is for trying rabbit after the embodiment 1 gained sesquiterpenoids Solution In The Treatment of acceptance 0.25% concentration, this group is cured substantially at medication postoperative infection position, the auditory meatus of 3 rabbits is had to also have a small amount of crust, the crust inspection that collection part retains finds no itch mite parasitism, also exist there are no worm's ovum, within the 14th day, check and find to cure completely.B group is for trying rabbit after the embodiment 1 gained sesquiterpenoids Solution In The Treatment of acceptance 0.40% concentration, this group is cured substantially at medication postoperative infection position, the auditory meatus of 1 rabbit is only had to also have a small amount of crust, the crust inspection that collection part retains finds no itch mite parasitism, also exist there are no worm's ovum, within the 14th day, check and find to cure completely.C group is for trying rabbit after the embodiment 1 gained sesquiterpenoids Solution In The Treatment of acceptance 0.50% concentration, this group is cured substantially at medication postoperative infection position, also the auditory meatus of 1 rabbit is only had to also have a small amount of crust, the crust inspection that collection part retains also finds no itch mite parasitism, also exist there are no worm's ovum, within the 14th day, check and find to cure completely.For D group for examination rabbit, after having injected ivermectin, achieving good result, cure rate 100%.And E group is for examination rabbit, after the mixed solution that adds water with glycerol is embrocated, from the scoring of gradient of infection, and infect in the efficiency of healing, before and after treatment, result is similar, gradient of infection changes not quite always, although the infection after the 7th day with recover scoring and decrease (result is relevant with collecting the calculating that part crust carries out gradient of infection for separating of itch mite) at every turn, from collect and the itch mite added up quantitatively, gradient of infection does not weaken.
Can draw from table 5, table 6, in A group, B group, C group, D group, within after medication 7 days, recovers to mark compared with blank group E group with treatment with the infection of 14 days, difference all extremely significantly, has statistical significance.From table 7 and table 8, can draw, contrast blank group E group, the therapeutic effect of other four groups is all remarkable, can both kill acarid.Experimental result shows, in g/mL, when in experimental group embodiment 1, the concentration of gained sesquiterpenoids is 0.25%, 0.40% and 0.50%, remarkable to the sick clinical therapeutic efficacy of psoroptes cuniculi, after acceptance treatment, recovers completely, without rebound phenomenon for examination rabbit.Meanwhile, to the left ear taking crust away with do not get crust auris dextra infection site compared with, all obtain good result after medication, statistical result zero difference (P<0.05), illustrate that this compound can immerse crust, play acaricidal action.
Experimental result shows, structure is such as formula the sesquiterpenoids shown in I, and miticidal effect is remarkable, has killing action, can be applied to better and prepare miticide animal demodicid mite, treatment animal acaricide.
The preparation of embodiment 4 emulsifiable concentrate
Get structure and add customary adjuvant such as formula the sesquiterpenoids shown in I, conventionally make emulsifiable concentrate.Used structure can be commercially available such as formula the sesquiterpenoids shown in I, and the method that also can provide according to the embodiment of the present invention 1 prepares,
The preparation of embodiment 5 suspending agent
Get structure and add customary adjuvant such as formula the sesquiterpenoids shown in I, conventionally make suspending agent.Used structure can be commercially available such as formula the sesquiterpenoids shown in I, and the method that also can provide according to the embodiment of the present invention 1 prepares,
The preparation of embodiment 6 powder
Get structure and add customary adjuvant such as formula the sesquiterpenoids shown in I, conventionally make powder.Used structure can be commercially available such as formula the sesquiterpenoids shown in I, and the method that also can provide according to the embodiment of the present invention 1 prepares,
The preparation of embodiment 7 granule
Get structure and add customary adjuvant such as formula the sesquiterpenoids shown in I, conventionally make granule.Used structure can be commercially available such as formula the sesquiterpenoids shown in I, and the method that also can provide according to the embodiment of the present invention 1 prepares,
The preparation of embodiment 8 ointment
Get structure and add customary adjuvant such as formula the sesquiterpenoids shown in I, conventionally make ointment.Used structure can be commercially available such as formula the sesquiterpenoids shown in I, and the method that also can provide according to the embodiment of the present invention 1 prepares,
Below be only the preferred embodiment of the present invention, it should be pointed out that above-mentioned preferred implementation should not be considered as limitation of the present invention, protection scope of the present invention should be as the criterion with claim limited range.For those skilled in the art, without departing from the spirit and scope of the present invention, can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (6)
1. structure is preparing the application in miticide such as formula the sesquiterpenoids shown in I,
2. application according to claim 1, is characterized in that, described demodicid mite is animal demodicid mite.
3. application according to claim 2, is characterized in that, described demodicid mite is itch mite.
4. application according to claim 1, is characterized in that, in g/mL, in described miticide, structure is 0.25% ~ 0.5% such as formula the mass body volume concentrations of the sesquiterpenoids shown in I,
5. application according to claim 1, is characterized in that, described miticide comprises structure such as formula the sesquiterpenoids shown in I and pharmaceutically acceptable adjuvant,
6. application according to claim 1, is characterized in that, the dosage form of described miticide is emulsifiable concentrate, suspending agent, powder, granule or ointment.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1416708A (en) * | 2002-12-11 | 2003-05-14 | 四川大学 | Eupatorine pesticide and its prepn |
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| CN1416708A (en) * | 2002-12-11 | 2003-05-14 | 四川大学 | Eupatorine pesticide and its prepn |
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| absolute stereochemistry of the insect antifeedant cadinene from eupatorium adenophorum;M J BORDOLOI ET AL;《TETRAHEDRON LETTERS》;19851231;第26卷(第4期);509-510 * |
| 入侵物种紫茎泽兰化学成分及生物活性研究进展;闫乾胜等;《北京师范大学学报(自然科学版)》;20061231;第42卷(第01期);70-73 * |
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