CN102397330B - Compound oil-in-water schizonepeta spike oil nanoemulsion composition and preparation method thereof - Google Patents
Compound oil-in-water schizonepeta spike oil nanoemulsion composition and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a compound oil-in-water schizonepeta spike oil nanoemulsion composition, which consists of the following raw materials in percentage by mass: 0.1 to 6.0 percent of schizonepeta spike oil, 0.1 to 5.0 percent of divaricate saposhnikovia root oil, 0.1 to 5.0 percent of weeping forsythiae capsule oil, 0.1 to 2.0 percent of peppermint oil, 0.01 to 0.65 percent of sodium houttuyfonate, 19.0 to 33.0 percent of surfactant and the balance of distilled water, wherein the total percentage by massweight of the raw materials is 100 percent. The nanoemulsion has the effects of relieving exterior syndrome by diaphoresis, clearing away heat and toxic materials, removing pathogenic wind and raising the nonspecific immunity of an organism, and is used for preventing and treating inappetence, increased temperature, cold intolerance and lack of power, which are caused by cold, and sore throat, cough, rhinorrhea, mucus even purulent secretion and the like fully filled in a nasal cavity, which are caused by upper respiratory tract infection, for livestock and poultryanimals.
Description
Technical field
The invention belongs to field of medicaments, relate to the prevention of the symptoms such as a kind of inappetence, fervescence, fear of cold that can cause because of flu for poultry is afraid of cold, the weak and laryngopharynx swelling and pain that causes because of upper respiratory tract infection, cough, rhinorrhea and compound recipe oil-in-water type mustard spike oil nano-emulsion for the treatment of and preparation method thereof.
Background technology
Flu is commonly encountered diseases and the frequently-occurring disease in the livestock and poultry cultivation process, particularly when suddenling change, more easily causes weather, can show as inappetence, general weakness, be reluctant to walk about, cough, rhinorrhea, nasal cavity be full of even pus sample secretions of mucus, severe patient can stop up nostril, when merging upper respiratory tract infection, symptom can increase the weight of, fervescence, fear of cold are afraid of cold, are trembled from head to foot, laryngopharynx swelling and pain etc., have a strong impact on the Production of Livestock and Poultry ability.It is viral that this disease pathogen mostly is, but understand secondary infection antibacterial, fungus, mycoplasma etc. when Abwehrkraft des Koepers descends, thereby increase the weight of the state of an illness.Raiser's economic benefit and cultivation confidence have been had a strong impact on.
Avian influenza is called for short bird flu, and it is a kind of a kind of infectious disease caused by bird flu virus, can infect the people, by International Office of Epizootics, is decided to be category A infectious disease, claims again fowl plague or European fowl plague.By the difference of pathogen type, it is divided into to highly pathogenic, low pathogenicity and non-pathogenic bird flu three major types.The non-pathogenic bird flu can not cause manifest symptom, produces antiviral antibody in the fowl body that only makes to catch an illness; The low pathogenicity bird flu can make birds slight respiratory symptom occur, and appetite reduces, and egg production descends, and fragmentary death occurs, affects its growth and production capacity; High pathogenic avian influenza is the most serious, and M & M is all high, and high mortality can reach 100%.Can cause respiratory tract, digestive tract, reproductive system or neural abnormal after poultry infects, sick fowl performance spirit is depressed, and two wings are sagging, cough, sneeze and shedding tears in a large number, feedstuff-meat ratio rising, weight loss; The hen broodiness strengthens, and egg production reduces; Head and face's edema, nervous symptoms appears in the later stage, last dead.
Swine influenza is a kind of acute respiration systematic infection disease of pig, and its feature shows as the burst cough, dyspnea, and heating reaches and lapses to rapidly.Primary disease autumn and winter season is multiple, seldom infects the people, often breaks out between pig, and infectiousness is very high but usually can not cause death.Be 2～7 days incubation period, the course of disease about 1 week.Sick pig their early stage performance lassitude, loss of appetite or absolutely useless, fervescence, often flock together together, and breathing is larger, dyspnea, cough, the movable minimizing, canthus and place, nostril have mucus to flow out.If treat not in time easy concurrent tracheitis, bronchitis, pneumonia and pleuritis etc., the case fatality rate of pig is raise.
The rabbit influenza is the commonly encountered diseases in the rabbit breeding process, although sickness rate is very high, but metainfective trouble rabbit symptom is difficult to the naked eye find out, general suddenly change or other reason just can show symptom clearly while causing hypoimmunity when weather, tremble with fear and shake as be afraid of, inappetence, spirit is depressed, cough, rhinorrhea, sneeze, there is secretions at the place, nostril, nose is dirty etc., body temperature can reach more than 40 ℃, be easy to merge pneumonia, cut open the most of sick rabbit of inspection, pulmonary all is the lobar pneumonia feature, the many places necrosis region is arranged, fall ill very anxious, often have little time treatment just dead.
Summary of the invention
The present invention is directed to the defect of the problems referred to above and prior art, a kind of pure botanical herbs preparation is provided, have no side effect, intestinal absorption rate and bioavailability are high, the prevention of the symptom such as the inappetence caused because of flu for poultry, fervescence, the fear of cold that stability is strong be afraid of cold, the weak and laryngopharynx swelling and pain that causes because of upper respiratory tract infection, cough, rhinorrhea and the compound oil-in-water schizonepeta spike oil nanoemulsion composition for the treatment of.Said composition is used safe, evident in efficacy.
The technical scheme that realizes the foregoing invention purpose is compound oil-in-water schizonepeta spike oil nanoemulsion composition, and it is comprised of the raw material of following mass percent:
Mustard spike oil 0.1%～6.0%
Oil of Radix Sapshnikoviae 0.1%～5.0%
Fructus Forsythiae oil 0.1%～5.0%
Oleum menthae 0.1%～2.0%
Sodium Houttuyfonate 0.01%～0.65%
Surfactant 19.0%～33.0%
Surplus is distilled water
The mass percent sum of above-mentioned raw materials is 100%;
The optimum ratio of compound oil-in-water schizonepeta spike oil nanoemulsion composition of the present invention:
Mustard spike oil 0.1%～5.5%
Oil of Radix Sapshnikoviae 0.1%～4.5%
Fructus Forsythiae oil 0.1%～4.0%
Oleum menthae 0.1%～1.8%
Sodium Houttuyfonate 0.01%～0.6%
Surfactant 20.5%～32.0%
Surplus is distilled water
The mass percent sum of above-mentioned raw materials is 100%.
The best proportioning of compound oil-in-water schizonepeta spike oil nanoemulsion composition of the present invention is: mustard spike oil nano-emulsion according to claim 1 comprises that mass percent is:
Mustard spike oil 1.5%
Oil of Radix Sapshnikoviae 0.6%
Fructus Forsythiae oil 0.5%
Oleum menthae 0.4%
Sodium Houttuyfonate 0.05%
Polyoxyethylene ether Oleum Ricini (EL-40) 23.0%
Distilled water 73.95%.
In the selection of surfactant, the present invention selects the nonionic surfactant of avirulence and good biocompatibility.Nonionic surfactant is more stable in solution, is not subject to the impact of strong electrolyte, inorganic salts, also is not subject to the impact of soda acid, and good with the compatibility of other surfactants, and haemolysis is less.In theory, the preparation of O/W type nanometer emulsion needs the HLB value of surfactant between 8～18, consider preparation technology's simplicity, be the easy formative of nano-emulsion and the stability of the nano-emulsion prepared, the present invention selects the liquid nonionic surfactant of HLB between 10～15.Preferably use polyoxyethylene ether Oleum Ricini (EL-40).
The dry spica that the mustard fringe is the labiate Herba Schizonepetae, be spike wheel umbrella inflorescence, slightly warm in nature, acrid in the mouth, enter the liver lung meridian, can be used for flu, headache, measles, skin infection from the beginning of etc. symptom.Accounted for 21 sides with mustard fringe person in "Fu Qingzhu works on obstetric" pandect 155 sides, accounted for 1/7th, dosage have weight minute, usage have give birth to fry not, when with its medicine compatibility, its effect has deduction more, mustard fringe medical value is original as seen.In the mustard fringe, containing the mustard spike oil, be light yellow or yellow volatile essential oil, main containing mustard fringe glycoside, pulegone, limonene etc.Data shows, the mustard spike oil not only has relieving the exterior syndrome by diaphoresis and the effect of dispeling the wind, and the humans and animals by influenza infection is also had to stronger protective effect, can effectively improve clinical symptoms, and misery palliates a disease.
The present invention be take mustard spike oil, oil of Radix Sapshnikoviae, Fructus Forsythiae oil, Oleum menthae and Sodium Houttuyfonate as combination, is that the symptom caused for flu can effectively be improved, and the body injury caused by virus is had to certain protective effect because the mustard spike oil has the effect of the loose wind that induces sweat; Oil of Radix Sapshnikoviae is the volatile oil extracted in the medicinal plants Radix Saposhnikoviae, induces sweat to dispel the wind into length, can dispersing wind and cold, can disperse wind heat again, and similar with the effect of mustard spike oil, two medicine fit applications effects are collaborative; Fructus Forsythiae oil is the volatile oil extracted from the medicinal plants Fructus Forsythiae, and the effect of heat-clearing and toxic substances removing is arranged, and cures mainly calentura from the beginning of, anemopyretic cold, heating, and the mood agitation, laryngopharynx swelling and pain etc., be used in this formula and can strengthen drug effect; Pharmaceutical composition suffering of the present invention is to disperse, cool to heat clearing away, clear light cool loose, for dispelling wind and heat pathogens product commonly used, can be used for the conjunctival congestion of having a headache, and the treatment of laryngopharynx swelling and pain, can effectively alleviate the various symptoms that flu causes; Sodium Houttuyfonate is plant antimicrobial, and the infection that staphylococcus aureus, hemophilus influenza, Candida albicans etc. are caused is effective.Also can improve serum properdin level, strengthen the effect of leukocytes phagocytic ability, thereby can improve the body non-specific immunity and resist the invasion and attack of pathogen.After the said medicine combination, without incompatibility, curative effect strengthens.
A further object of the invention is to provide the preparation method of compound oil-in-water schizonepeta spike oil nanoemulsion composition, specifically comprises the following steps:
1) accurately take the quality of surfactant, mustard spike oil, oil of Radix Sapshnikoviae, Fructus Forsythiae oil, Oleum menthae, Sodium Houttuyfonate, distilled water by formula, standby;
2) by the mustard spike oil of described amount, oil of Radix Sapshnikoviae, Fructus Forsythiae oil, Oleum menthae mixing and stirring, as oil phase;
3) surfactant of described amount joined in the middle of oil phase and stir;
4) Sodium Houttuyfonate of described amount is dissolved in after the distilled water of described amount as water, at room temperature stir rapidly oil phase and surfactant mixture, slowly drip distilled water when stirring, until system is transparent liquid, obtain compound oil-in-water schizonepeta spike oil nanoemulsion composition.
The present invention detects through transmission electron microscope, and droplet diameter distribution is between 1～100nm, and outward appearance is yellow or flaxen transparency liquid, has good stability:
1, ageing stability
This compound oil-in-water schizonepeta spike oil nanoemulsion composition after storage, through the lasting clear of check outward appearance, without breakdown of emulsion situations such as muddiness or precipitations, shows that ageing stability is good under room temperature nature change condition.
2, heat storage stability
Store 20d by after this compound oil-in-water schizonepeta spike oil nanoemulsion composition sealed packaging, being placed in 50 ℃ of calorstats, observe every the 5d sampling.Result shows, after this nano-emulsion heat storage, outward appearance still keeps clear, without breakdown of emulsion situations such as muddiness or layerings, illustrates that heat storage stability is good.
3, anti-freeze-stable
By this compound oil-in-water schizonepeta spike oil nanoemulsion composition in refrigerator-10 ℃ preserve one week after.Its taking-up is returned to room temperature.This nano-emulsion can be liquid by solid-state thawing, through checking still clear of outward appearance, places after one week and continues check, without breakdown of emulsion situations such as muddiness or precipitations, shows that anti-freeze-stable is good.
4, accelerated stability
This compound oil-in-water schizonepeta spike oil nanoemulsion composition is placed in to test tube, sealing, under the rotating speed of 15000r/min centrifugal 20 minutes, outward appearance clear still after the dilution check, without breakdown of emulsion situations such as muddiness or precipitations.
5, light stability experiment
This compound oil-in-water schizonepeta spike oil nanoemulsion composition of part is loaded in vial, and sealing is placed under daylight, and light at room temperature, according to 10d, samples respectively in 1d, 3d, 5d, 10d.Show that through the dilution check this nanoemulsions keeps clear, without breakdown of emulsion situations such as muddiness or layerings, shows that light stability is good.
The effect of the symptoms such as compound oil-in-water schizonepeta spike oil nanoemulsion composition of the present invention has prevention and treatment the poultry inappetence, fervescence, the fear of cold that cause because of flu are afraid of cold, the weak and laryngopharynx swelling and pain that causes because of upper respiratory tract infection, cough, rhinorrhea.
Usage: oral or drinking-water, once-a-day, each 0.1ml.
Compound oil-in-water schizonepeta spike oil nanoemulsion composition of the present invention compared with prior art, has the following advantages:
1) good water solubility.Can be in water infinite dilution and can breakdown of emulsion, can be used as liquid additive to use, for preventing and treating the livestock and poultry cold disease;
2) active component is pure botanical herbs composition, has no side effect and the antibiotic remains problem;
3) thermodynamic stability is high.Store not phase-splitting in-10 ℃ and 50 ℃ of temperature range scopes, do not precipitate, not muddy, the breakdown of emulsion situation does not appear, good stability;
4) absorbance is high.Nano level fat drips more easily and is absorbed by intestinal mucosa, and the enhancing of histiocytic affinity, and absorbance is higher than former medicine oil;
5) can avoid the first pass effect of liver after intestinal absorption, avoid the degraded of liver drug enzyme, the bioavailability of medicine is improved;
6) method technique is simple, with low cost, is applicable to large-scale production.
The specific embodiment
Below by drug safety, test and the test of pesticide effectiveness is further set forth the beneficial effect of medicine of the present invention.
Test example 1The test of compound recipe mustard spike oil nano emulsion composition drug safety
Choose 40 of the healthy mices of about body weight 20g, it is divided into to two groups of matched group and experimental grouies, 20 every group at random.Control group mice gavage every day normal saline 0.3ml, the compound recipe mustard spike oil nano-emulsion of experimental group gavage Isodose, every day gavage once, continuously gavage is one week.Observe during this time active state and the health status of mice every day, and keep a record; After last administration 6h, mice is put to death and cuts open inspection, observe the pathological change of each internal organs, and keep a record.
Result shows: two groups of mice active situation and health status are all normal, cut open after inspection each internal organs also without pathological changes extremely, and zero difference between two groups, show that this nanoemulsions safety is good.
Test example 2Compound recipe mustard spike oil nano-emulsion is for the grippal preventive effect contrast test of rabbit
Choose 60 of the young rabbits that about a monthly age, body weight is close, by its be divided at random negative control group, without three groups of medicine matched group and compound recipe mustard spike oil nano-emulsion groups, 20 every group.20 young rabbits of negative control group are raised in No. 1 rabbit home, and raise by mode standard, drink clean tap water every day; 40 young rabbits without medicine matched group and compound recipe mustard spike oil nano-emulsion group are raised in No. 2 rabbit homes, wherein without the medicine matched group, freely drink clean tap water, and compound recipe mustard spike oil nano-emulsion group is freely drunk the compound recipe mustard spike oil nanoemulsions after 500 times of dilutions.Adjust the temperature and humidity of No. 2 rabbit homes after one week, make the temperature difference at 20 ℃ ~ 30 ℃ range changings, humidity changes in 60% ~ 80% scope, and daily variation twice changes two days continuously, with the manual simulation environment, makes young rabbit flu.Between feeding period, observe young rabbit invasion situation, activity situation every day, and make a record.
Criterion:
If sneeze, cough, place, nostril appear in young rabbit, the mucus of abnormal secretion is arranged, inappetence or abolishment, spirit is depressed, and the basal part of the ear such as sends out cool at the flu disease or died can be diagnosed as flu.
Table 1Compound recipe mustard spike oil nano-emulsion is for the preventive effect comparative test result of rabbit flu
By Biao Kede: when environmental catastrophe, without the young rabbit flu of medicine group incidence rate, be 65%, mortality rate is 35%; Compound recipe mustard spike oil nano-emulsion flu incidence rate is 30%, and mortality rate is 5%; Result shows, when change in weather, compound recipe mustard spike oil nano-emulsion has significant preventive effect to the rabbit flu.
Below further set forth composition and the preparation method of medicine of the present invention by specific embodiment.
Embodiment 1
A kind of compound oil-in-water schizonepeta spike oil nanoemulsion composition, the quality of each component:
Mustard spike oil 1.5g, oil of Radix Sapshnikoviae 0.6g, Fructus Forsythiae oil 0.5g, Oleum menthae 0.4g, Sodium Houttuyfonate 0.05g, polyoxyethylene ether Oleum Ricini (EL-40) 23.0g, distilled water 73.95g.
Above-mentioned each component is made compound oil-in-water schizonepeta spike oil nanoemulsion composition, comprises the following steps:
1) accurately take the quality of surfactant, mustard spike oil, oil of Radix Sapshnikoviae, Fructus Forsythiae oil, Oleum menthae, Sodium Houttuyfonate, distilled water by formula, standby;
2) by the mustard spike oil of described amount, oil of Radix Sapshnikoviae, Fructus Forsythiae oil, Oleum menthae mixing and stirring, as oil phase;
3) surfactant of described amount joined in the middle of oil phase and stir;
4) Sodium Houttuyfonate of described amount is dissolved in after the distilled water of described amount as water, at room temperature stir rapidly oil phase and surfactant mixture, slowly drip distilled water when stirring, until system is transparent liquid, obtain compound oil-in-water schizonepeta spike oil nanoemulsion composition.
Embodiment 2
Mustard spike oil 2.5g, oil of Radix Sapshnikoviae 1.5g, Fructus Forsythiae oil 1.0g, Oleum menthae 1.0g, Sodium Houttuyfonate 0.15g, polyoxyethylene ether Oleum Ricini (EL-40) 25.0g, distilled water 68.85g.
Embodiment 3
Mustard spike oil 6.0g, oil of Radix Sapshnikoviae 0.2g, Fructus Forsythiae oil 0.2g, Oleum menthae 0.1g, Sodium Houttuyfonate 0.1g, polyoxyethylene ether Oleum Ricini (EL-40) 27.0g, distilled water 66.4g.
Embodiment 4
Mustard spike oil 4.0g, oil of Radix Sapshnikoviae 1.0g, Fructus Forsythiae oil 0.5g, Oleum menthae 0.1g, Sodium Houttuyfonate 0.25g, polyoxyethylene ether Oleum Ricini (EL-40) 28.0g, distilled water 66.15g.
Embodiment 5
Mustard spike oil 3.2g, oil of Radix Sapshnikoviae 1.4g, Fructus Forsythiae oil 0.6g, Oleum menthae 0.6g, Sodium Houttuyfonate 0.01g, polyoxyethylene ether Oleum Ricini (EL-40) 22.8g, distilled water 71.39g.
Embodiment 6
Mustard spike oil 3.5g, oil of Radix Sapshnikoviae 0.5g, Fructus Forsythiae oil 0.2g, Oleum menthae 1.8g, Sodium Houttuyfonate 0.2g, polyoxyethylene ether Oleum Ricini (EL-40) 25.0g, distilled water 68.8g.
Embodiment 7
Mustard spike oil 1.0g, oil of Radix Sapshnikoviae 0.5g, Fructus Forsythiae oil 5.0g, Oleum menthae 0.1g, Sodium Houttuyfonate 0.12g, polyoxyethylene ether Oleum Ricini (EL-40) 26.5g, distilled water 66.78g.
Embodiment 8
Mustard spike oil 1.2g, oil of Radix Sapshnikoviae 2.5g, Fructus Forsythiae oil 0.5g, Oleum menthae 0.5g, Sodium Houttuyfonate 0.02g, polyoxyethylene ether Oleum Ricini (EL-40) 33.0g, distilled water 62.28g.
Embodiment 9
Mustard spike oil 5.0g, oil of Radix Sapshnikoviae 0.1g, Fructus Forsythiae oil 0.5g, Oleum menthae 1.0g, Sodium Houttuyfonate 0.03g, polyoxyethylene ether Oleum Ricini (EL-40) 29.4g, distilled water 63.97g.
Embodiment 10
Mustard spike oil 3.0g, oil of Radix Sapshnikoviae 0.5g, Fructus Forsythiae oil 0.5g, Oleum menthae 0.3g, Sodium Houttuyfonate 0.06g, polyoxyethylene ether Oleum Ricini (EL-40) 30.0g, distilled water 65.64g.
Claims (1)
1. a compound oil-in-water schizonepeta spike oil nanoemulsion composition that is used for the treatment of livestock and poultry cold, is characterized in that, the raw material of following mass percent, consists of:
Mustard spike oil 0.1%～6.0%, oil of Radix Sapshnikoviae 0.1%～5.0%, Fructus Forsythiae oil 0.1%～5.0%, Oleum menthae 0.1%～2.0%, Sodium Houttuyfonate 0.01%～0.65%, surfactant 19.0%～33.0%, surplus are distilled water, and the mass percent sum of above-mentioned raw materials is 100%;
Described surfactant is the polyoxyethylene ether Oleum Ricini.
2. the compound oil-in-water schizonepeta spike oil nanoemulsion composition that is used for the treatment of livestock and poultry cold according to claim 1, is characterized in that, the raw material of following mass percent, consists of:
Mustard spike oil 0.1%～5.5%, oil of Radix Sapshnikoviae 0.1%～4.5%, Fructus Forsythiae oil 0.1%～4.0%, Oleum menthae 0.1%～1.8%, Sodium Houttuyfonate 0.01%～0.6%, surfactant 20.5%～32.0%, surplus are distilled water, and the mass percent sum of above-mentioned raw materials is 100%.
3. the compound oil-in-water schizonepeta spike oil nanoemulsion composition that is used for the treatment of livestock and poultry cold according to claim 1, is characterized in that, the raw material of following mass percent, consists of:
Mustard spike oil 1.5%, oil of Radix Sapshnikoviae 0.6%, Fructus Forsythiae oil 0.5%, Oleum menthae 0.4%, Sodium Houttuyfonate 0.05%, surfactant 23.0%, distilled water 73.95%.
4. the compound oil-in-water schizonepeta spike oil nanoemulsion composition that is used for the treatment of livestock and poultry cold according to claim 1, is characterized in that, the particle diameter of this nano-emulsion is between 1～100nm.
5. the preparation method that is used for the treatment of the compound oil-in-water schizonepeta spike oil nanoemulsion composition of livestock and poultry cold claimed in claim 1, is characterized in that, specifically comprises the following steps:
1) accurately take the quality of surfactant, mustard spike oil, oil of Radix Sapshnikoviae, Fructus Forsythiae oil, Oleum menthae, Sodium Houttuyfonate, distilled water by formula, standby;
2) by the mustard spike oil of described amount, oil of Radix Sapshnikoviae, Fructus Forsythiae oil, Oleum menthae mixing and stirring, as oil phase;
3) surfactant of described amount joined in the middle of oil phase and stir;
4) Sodium Houttuyfonate of described amount is dissolved in after the distilled water of described amount as water, at room temperature stir rapidly oil phase and surfactant mixture, slowly drip distilled water when stirring, until system is transparent liquid, obtain compound oil-in-water schizonepeta spike oil nanoemulsion composition.
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