A kind of oil-in-water type citronella oil nano-emulsion and preparation method thereof
Technical field
The invention belongs to medicine and filed of daily-use chemical industry, relate to a kind of analgesia that has, anophelifuge, antiinflammatory, antibiotic, the citronella oil novel form of adjusting emotional function is specifically related to a kind of oil-in-water type citronella oil nano-emulsion and preparation method thereof.
Background technology
Herba Cymbopogonis Citrari is perennial herb, and main product spreads all over the torrid areas, Asia in India and Sri Lanka, and all there is cultivation in the south China province.The acrid in the mouth hardship, warm in nature, the citrus scented that tool is strong has the cold expelling dampness removing, the effect of relieving cough and asthma.Begin commercial the application from this century, be mainly used in medical treatment, health care and dietetic therapy.Citronella oil can purify and improve emotion, can relieve depressed mood.Warm draft flavor makes the people be full of simple and natural fragrant fragrant environment, can make popular feeling feelings joyful.It is exactly anthelmintic that Herba Cymbopogonis Citrari also has a most important characteristic, pre-protection against insect and mosquito bite.Distill the Herba Cymbopogonis Citrari hydrosol that obtains by Herba Cymbopogonis Citrari. have pleasant Fructus Citri Limoniae delicate fragrance, be used for suitable summer spraying or incense.According to Herba Cymbopogonis Citrari products such as the foot smell prevention hydrosol of the characteristics of Herba Cymbopogonis Citrari development, mosquito repellent liquid, crowd with age 18-22 year tests for the main object of observation, prove that Herba Cymbopogonis Citrari hydrosol safe, pure and fresh, with low cost is used for all kinds of fungal infection of prophylactic treatment, eliminates the unusual smell, and has very obvious effects.Raising along with global environmental consciousness, the harm of chemical insecticide, antibacterial has obtained the whole mankind's extensive attention, re-recognizes research antibiotic property that natural plants had, insect-repellent and people's health-care effect is also become the various countries scientist and send out research worker's focus of attention.
The Herba Cymbopogonis Citrari quintessence oil has stronger inhibition effect to the pathogen in some plant pathogenic fungis and the food, it has stronger bacteriostasis to grey mold, as long as postharvest fruit and vegetable mainly the inhibition effect of pathomycete, and is carried out the comparison of system to its bacteriostatic activity, can be used as biological fruit and vegetable fresh-keeping agent.
Because plants essential oil has low toxicity, do not pollute grain and environment, insect is difficult for producing resistance, simple in structure, fragrant odour, the grain taste is not had advantages such as influence, and exploitation will become important ingredient in the green reserves engineering as the reserves protective agent.Domestic and foreign literature has reported that plants essential oil has effects such as repellent, stifling and population inhibition to multiple grain storage pest and agricultural pests.
At present the major product of citronella oil is Herba Cymbopogonis Citrari quintessence oil and Herba Cymbopogonis Citrari hydrosol, and the Herba Cymbopogonis Citrari hydrosol is poorly soluble, and the Herba Cymbopogonis Citrari quintessence oil is volatile, the product physical instability, be difficult to preserve, in water difficulties in dispersion, availability is not high.
Summary of the invention
At problems of the prior art and defective, the object of the present invention is to provide a kind of content evenly accurately, steady quality, availability is higher and prepare easy nano-emulsion.
The technical scheme that realizes the foregoing invention purpose is a kind of citronella oil nano-emulsion, this nano-emulsion particle diameter is between 1~100nm, its composition and mass percent thereof are: citronella oil 0.01%~17.6%, surfactant 23%~44%, cosurfactant 6.4%~16.5%, oil 0~10% surplus are distilled water, and the mass percent sum of above-mentioned raw materials is 100%.
The optimum ratio of citronella oil nano-emulsion of the present invention is: citronella oil 1.2%~10.5%, surfactant 25%~35%, cosurfactant 6.4%~12.5%, oil 0.1~3% surplus are distilled water, and the mass percent sum of above-mentioned raw materials is 100%.
According to the formation mechanism of nano-emulsion, when the required HLB value of hydrophile-lipophile balance (HLB) value and the oil of surfactant equates or be close, form the highly stable nano-emulsion of character easily.The present invention selects for use toxicity less relatively according to the method, be not subject to electrolyte, inorganic salts and soda acid influence and with the good castor oil hydrogenated polyoxyethylene ether (40) of the compatibility of other surfactants (RH-40), tween 80 is as surfactant.
Cosurfactant is to be used for the HLB value of reconciliation statement surface-active agent, makes the easier formation nano-emulsion of surfactant and oil.The present invention selects 1 for use, and 2-propylene glycol, dehydrated alcohol are regulated the HLB value as cosurfactant.Form mechanism according to nano-emulsion, oil is that the matching surface activating agent participates in forming the stabilized nanoscale breast, the HLB value of isopropyl myristate (IPM) and the HLB value of tween 80 are approaching, the HLB value of ethyl acetate and the HLB value of RH-40 are near easily forming the stabilized nano breast, so the oil that the present invention selects for use is isopropyl myristate (IPM), ethyl acetate.
Surfactant and cosurfactant optimum quality ratio are 5: 1 in the citronella oil nano-emulsion antibacterial drug of the present invention.
In the citronella oil nano-emulsion antibacterial drug of the present invention, surfactant and cosurfactant sum are 8: 2 with the best in quality ratio of oil.
The present invention adopts the pseudo-ternary phase diagram method to filter out optimum formula to prepare the citronella oil nano-emulsion.When surfactant and cosurfactant mass ratio are 5: 1, surfactant and cosurfactant sum are the nano-emulsion district maximum that formed at 8: 2 o'clock with the mass ratio of oil, and the most stable, drug loading is the highest simultaneously.Used castor oil hydrogenated polyoxyethylene ether (40) (RH-40) in the prescription, tween 80 toxicity is less relatively, is not subject to the influence of electrolyte, inorganic salts and soda acid; The nano-emulsion emulsifying capacity of doing cosurfactant formation with 1,2 one propylene glycol, dehydrated alcohol is strong, and it also is used for regulating the HLB value in addition; The HLB value of isopropyl myristate (IPM), ethyl acetate and the HLB value of tween 80 are approaching, easily form the stabilized nano breast, their molecular weight is little in addition, the effect and the cosurfactant of micromolecule oil phase are similar, easily be embedded in the surfactant, form interfacial film with it jointly, solubilising power is greater than the macromole oil phase; The shared percentage ratio of water is high more in the nano-emulsion system, and the probability that forms nano-emulsion is big more.
Another object of the present invention provides the preparation method of citronella oil nano-emulsion, it is characterized in that, specifically may further comprise the steps:
1) it is standby to take by weighing citronella oil, surfactant, cosurfactant, oil, distilled water;
2) be dissolved in citronella oil in the cosurfactant fully earlier;
3) add the surfactant mixing, standby;
4) slowly drip distilled water in the solution of step 3) preparation, constantly stir in the time of dropping, until the system that forms homogeneous transparent, promptly.
Citronella oil nano-emulsion antibacterial drug of the present invention is the liquid of faint yellow clear, and long-term the placement do not have crystallization to separate out under low temperature-40C, do not have muddy phenomenon under 60 ℃ of hot conditionss yet, as seen is a kind of stable dosage form; And preparation method is simple, energy consumption is low, toxicity is little, safe, do not need special installation to can be used for producing in enormous quantities, thereby be used for medicine and filed of daily-use chemical industry.
Citronella oil nano emulsion composition of the present invention have analgesia, anophelifuge, antipruritic, antiinflammatory, antibiotic, regulate effect such as emotion, can treat headache, migraine, sore throat, fever, diseases such as cough, but be sprayed on indoor deodorization, sterilization, anthelmintic also can encourage emotion, alleviates melancholy uneasy.
The using method of citronella oil nano-emulsion of the present invention is: when using as fruit and vegetable fresh-keeping agent, the citronella oil nano-emulsion with 10.5% dilutes with tap water according to 1: 250 ratio, and the aerosol apparatus of then it being packed into is sprayed on fruit and vegetable surfaces and gets final product; During as anophelifuge and air purifying preparation use, direct citronella oil nano-emulsion with 10.5% is sprayed in the air, can use as one feels fit according to floor space and personal like, and recommended dose is 0.1ml/m
2When being used for the treatment of headache, the citronella oil nano-emulsion with 10.5% is applied to temple and forehead position, massages gently, absorbs fully to it to get final product; Be used for antiinflammatory, when antipruritic, antibiotic, it directly be applied to the skin affected part, smeared once in per 1~6 hour, can determine number of times and consumption according to the affected part symptom.
Compared with prior art, of the present invention having the following advantages:
1) has characteristics such as viscosity is low, good stability, dispersibility is strong, absorption is rapid, targeting is strong, can improve bioavailability of medicament, prolong drug half-life, reduction toxic and side effects in vivo when for oral administration.
2) it also has the characteristics that surface tension is low, wellability is good, so medicine well is attached on the antibacterial, penetrates into its metabolism of antibacterial internal interference and brings into play antibacterial or bactericidal action.
Description of drawings
The transmission electron microscope picture of Fig. 1 citronella oil nano-emulsion of the present invention.
The particle size distribution figure of Fig. 2 citronella oil nano-emulsion of the present invention.
The specific embodiment
Below the concrete test example that provides by the inventor further specify beneficial effect of the present invention.
The study on the stability of test example 1 citronella oil nano-emulsion
1) the high speed centrifugation test is to the influence of nano-emulsion stability
In centrifuge tube in, put in high speed centrifuge in right amount by sealing orifice for the citronella oil nano-emulsion of getting preparation, carries out centrifugally with the rotating speed of 12000r/min, still keeps clear through the centrifugal nanoemulsions of 20min, do not see that the citronella oil nano-emulsion is separated out and the profit lamination.
2) light stability test
Nano-emulsion of the present invention is packed in the vial in right amount, and room temperature is placed under (4500 ± 500) the lx illumination condition of sealing back, respectively at 0d, 5d, the 10d observation of taking a sample.The result shows that emulsion keeps the clear outward appearance, does not see phenomenons such as layering and breakdown of emulsion.
3) reserved sample observing experiment
Get part citronella oil nano-emulsion, be sub-packed in several vials, placing respectively after the sealing keeps sample under refrigerator-40C, room temperature, the 60 ℃ of conditions investigates 60d, observes every the 5d sampling.The result shows that this nano-emulsion all keeps the outward appearance of clear under three kinds of temperature conditions, and breakdown of emulsion, layering and crystallization are not separated out.Transmission electron microscope is observed down, and the drop of citronella oil nano-emulsion is spherical in shape, and its particle diameter people is little to be 1~100nm, and is evenly distributed, and favorable dispersibility is specifically seen Fig. 1 and Fig. 2.
The analgesia effect experiment of test example 2 citronella oil nano-emulsions
1 experimental technique
Adopt the mice hot plate method: regulate the electric heating constant temperature water tank temperature, it is remained on about 550C, a large beaker is put into the about 3min of electric heating constant temperature water tank, make cup and water equality of temperature.The Healthy female white mice is put into cup, and be the threshold of pain index incubation period of licking the metapedes reaction with white mice, observes and write down it pain reaction required time takes place.Reject less than 5s or greater than the white mice of 30s incubation period.Select 30 white mice for use, divide 3 groups at random, be i.e. citronella oil nano-emulsion group, blank nano-emulsion group and negative control group, every group of 10 white mice.Negative control group is smeared the normal saline of equivalent.Each group will be tested medicine respectively and be embrocated in white mice extremity 1min then, measure its time incubation period behind the 30min again.
2 judgment criteria
Be the threshold of pain index incubation period of licking the metapedes reaction with white mice, observes and write down it pain reaction required time takes place.Effective percentage is contrast with the negative control group, and computing formula is: effective percentage=(respectively organizing one negative control group time incubation period of time incubation period)/negative control group time incubation period.
3 experimental results
Table 1 citronella oil nano-emulsion is to the analgesic activity (N=10) of mice
The result shows that citronella oil nano-emulsion and negative control group compare, and treatment time and effective percentage difference are extremely remarkable, and mice is had significant analgesia role.
Test example 2 citronella oil nano-emulsion anophelifuge effect experiments
1 material
The citronella oil nano-emulsion is a product of the present invention; Matched group is a floral water; Aedes albopictus is the emergence 4-6 age in days female mosquito of not sucking blood; Kunming mouse body weight (20 ± 2) g, large ear rabbit body weight 2-2.5kg.
2 methods
The test of laboratory anophelifuge is put into 300 female mosquitos in 30cm * 30cm * 40cm mosquito cage.
Laboratory temperature 26-270C, relative humidity 60%~70%.The repelling effect standard: the blank group mosquito number of sucking blood is qualified more than promptly declaring the mosquito attack more than 30, and the experimental group repelling effect is effective; Promptly declare the repellent inefficacy as long as there is a mosquito to suck blood, calculate effective protecting time.
2.1 mice repellency test
Prepare 5 cages test mosquito, 5 mouse web portions are individually fixed on 8cm * 12cm plank up, cut off ventral seta, expose 2.5cm * 4cm skin, wrap up with kraft paper at other positions, tries preceding 8,7,6,5h evenly coats reagent by the consumption of 0.1mL/cm2 respectively in exposing abdominal part, and 1 Mus makes blank in addition.In 17:00-18:00 5 mices to be measured are respectively put into a mosquito cage simultaneously and park 2min, the observed and recorded mosquito stings thorn quantity.Floral water with quadrat method blank testing nano-emulsion group and equivalent is made comparisons.Every group is repeated 5 times, calculates the average effective guard time.
2.2 human body repellency test
The test of pesticide effectiveness is carried out in indoor harmacological effect evaluation methodology according to GB/T17322.10-1998 agriculture chemical registration hygienic insecticide.5h before the examination; the experimenter wears the altex glove that the back of the hand exposes 20cm2; press 0.1mL/cm2 dosage; left hand is smeared reagent; the right hand is made blank, between 17:00-19:00 hands is stretched into and stops 2min in the cage, every 30min test 1 time; till having 1 mosquito to begin to attack, the record effective protecting time.Test repeats to calculate the average effective guard time more than 5 times.
3 results
3.1 the test of laboratory mice repellency test laboratory anophelifuge shows that the frequency of biting of 5.3h Aedes albopictus is 0 behind the coating; And 5 tests of the blank nano-emulsion group of the no medicine of contrast are all stung by thorn; Citronella oil nano-emulsion average effective guard time is 5.5h, and matched group floral water effective protecting time is 3.8h (table 2).Illustrate that citronella oil nano-emulsion repelling effect all has repellent effect preferably than matched group.
Table 2 citronella oil nano-emulsion is to the repellent effect of Aedes albopictus
3.2 laboratory human body repellency test test shows, behind coating in the 5.3h, the frequency of biting of Aedes albopictus is 0, the 6h and bites 2 times, and the average effective guard time is 5.5h, and is similar to mice repellency test effect.
Below in conjunction with the specific embodiment, further set forth the present invention
Embodiment 1 preparating liquid concentration is 0.01% citronella oil nano-emulsion
The concrete operations step is:
1) be dissolved in citronella oil in the cosurfactant fully earlier;
2) add the surfactant mixing, standby;
3) slowly drip distilled water to step 2) in the solution of preparation, constantly stir in the time of dropping, until the system that forms homogeneous transparent, promptly.
Embodiment 2 preparating liquid concentration are 0.4% citronella oil nano-emulsion
Embodiment 3 preparating liquid concentration are 0.5% citronella oil nano-emulsion
Embodiment 4 preparating liquid concentration are 1% citronella oil nano-emulsion
Embodiment 5 preparating liquid concentration are 1.2% citronella oil nano-emulsion
Embodiment 6 preparating liquid concentration are 1.5% citronella oil nano-emulsion
Embodiment 7 preparating liquid concentration are 4.2% citronella oil nano-emulsion
Embodiment 8 preparating liquid concentration are 4.3% citronella oil nano-emulsion
Embodiment 9 preparating liquid concentration are 4.4% citronella oil nano-emulsion
Embodiment 10 preparating liquid concentration are 5% citronella oil nano-emulsion
Embodiment 11 preparating liquid concentration are 8% citronella oil nano-emulsion
Embodiment 12 preparating liquid concentration are 10.5% citronella oil nano-emulsion
Embodiment 13 preparating liquid concentration are 17.6% citronella oil nano-emulsion