CN102600304A - Nanoemulsion composition for treating mycoplasma pneumonia of livestock and preparation method of nanoemulsion composition - Google Patents
Nanoemulsion composition for treating mycoplasma pneumonia of livestock and preparation method of nanoemulsion composition Download PDFInfo
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- CN102600304A CN102600304A CN2012100572660A CN201210057266A CN102600304A CN 102600304 A CN102600304 A CN 102600304A CN 2012100572660 A CN2012100572660 A CN 2012100572660A CN 201210057266 A CN201210057266 A CN 201210057266A CN 102600304 A CN102600304 A CN 102600304A
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Abstract
The invention discloses a nanoemulsion composition for treating mycoplasma pneumonia of livestock, which consists of raw materials including, by mass percent, from 0.1 to 8.0% of amyris oil, from 0.1 to 5.0% of vitex oil, from 0.1 to 3.0% of perilla oil, from 0.1 to 2.0% of bupleurum oil, from 0.01 to 0.1% of allicin, from 0.1 to 4.0% of tiamulin fumarate, from 19.0% to 31.0% of surfactant and the balance distilled water. The sum of the mass ratios of the ingredients is 100%. The nanoemulsion composition has effects of dilating the trachea of the livestock, suppressing cough reflex, increasing immunity of the organism, resisting inflammation and killing mycoplasma pneumoniae or other mixed infected causative agent, can be used for preventing and curing respiratory diseases including chronic respiratory diseases of the livestock, mycoplasma pneumoniae of swine, porcine contagious pleuropneumonia and the like, is fine in stability, is high in intestinal absorption utilization rate after being orally taken, can avoid liver first pass effect, and is remarkable in curative effect.
Description
Technical field
The invention belongs to field of veterinary, relate to a kind of nano emulsion composition that can be used for respiratory system disease treatments such as fowl chronic respiratory tract disease, mycoplasma pneumoniae of swine and contagious pleuropneumonia and preparation method thereof.
Background technology
Respiratory tract disease is commonly encountered diseases and the frequently-occurring disease in the livestock and poultry cultivation process.Particularly in recent years, along with expanding economy, the raising of people's level of consumption, market continues to increase the demand of meat, egg, milk, and tradition is cultured gradually and is changed to modernized intensive culture, and livestock and poultry cultivation quantity increases, and scale is unprecedented.Add that present China management system is also not sound; The selections that antibiotic abuse carries out Resistant strain etc. cause the sickness rate of livestock and birds respiratory disease high always, and case fatality rate also constantly rises; Aquaculture cost also constantly increases, and becomes the comparatively serious problem that China's livestock and poultry cultivation is supported in puzzlement.
Chronic respiratory disease is a kind of contagious disease that is caused by chicken virus mycoplasma (MG) infection, and annual each Ji Junke takes place, and is the most serious with severe winter and early spring.Sending hello sound, cough, rhinorrhea and the swelling of hole portion during with breathing is Clinical symptoms, as is simple infection, generally is recessive process, and it is slower to fall ill, and the course of disease is longer, so the chronic respiratory tract disease of gaining the name.Because primary disease can cause the growth promoter of body, so the fowl raising phase is prolonged, the price of deed reduces, and laying hen crowd laying rate can descend 10% ~ 45%, and raiser's economy is suffered a loss greatly.Because Abwehrkraft des Koepers descends, other cause of diseases of the normal concurrent infection of primary disease (like escherichia coli etc.), cause case fatality rate high.
Swine enzootic pneumonia is a kind of chronic respiratory infectious disease that is caused by mycoplasma infection; Sick pig mainly shows asthma and cough; Cut open the inspection pathological change and concentrate on the thoracic cavity; Clear with disease strong joint portion boundary, two leaf disease change portions are symmetry and mostly are confined to sharp leaf, lobus cardiacus and middle leaf about lung, have solid being felt as of pancreas appearance to look the disease pathological changes.Primary disease can cause pig poor growth even stagnation, and efficiency of feed utilization descends, and fattening period prolongs.
Present numerous raisers mainly adopt on the traditional methods such as Chinese powder medicine spice and injection intramuscular injection to the treatment of livestock and poultry mycoplasma pneumonia; Be easy to occur stirring uneven phenomenon during the Chinese powder medicine spice; The animals eat that causes too much; The animals eat that has less than situation, and often appetite is low after the poultry morbidities, the drug effect utilization rate can be very low; Injection has better therapeutic effect, but big to the irritability of animal, wastes time and energy, because the resistance of animal makes the very inconvenience that operates; Rue oil. among the present invention has the curative effect of good curing respiratory system disease, but at present people mainly are confined on the former medicine its utilization, is main with drop pill on the market, and other dosage forms almost do not have.Particularly in the herding field, the utilization of Rue oil. is not starting also, and its medical value fails to embody in animal, and medicinal field is narrow, has directly influenced the utilization and extention of Rue oil..Therefore, to above-mentioned situation, thereby be necessary with the Rue oil. to be that main active and composite other treatment medicine are developed the treatment that a kind of novel form is used for respiratory illness of livestock and poultry, in order to serve animal husbandry.
Summary of the invention
The present invention is directed to the defective of the problems referred to above and prior art; Provide a kind of absorbance high; Bioavailability is good; A kind of oil-in-water type nano emulsion composition of respiratory system diseases such as fowl chronic respiratory tract disease, mycoplasma pneumoniae of swine and contagious pleuropneumonia is treated in strong being used to of stability, said composition safely, have no side effect and significant curative effect arranged.
The technical scheme that realizes the foregoing invention purpose is this nano emulsion composition, is made up of following raw materials by weight percentage:
Rue oil. 0.1%～8.0%
Oleum Viticis Negundo 0.1%～5.0%
Perilla oil 0.1%～3.0%
Oleum Bupleuri 0.1%～2.0%
Garlicin 0.01%～0.1%
Fumaric acid tiamulin 0.1%～4.0%
Surfactant 19.0%～31.0%
Surplus is a distilled water
Above-mentioned total component is 100%.
On surfactant selection, the present invention selects the nonionic surfactant of avirulence and good biocompatibility for use.Nonionic surfactant is more stable in solution, is not subject to the influence of strong electrolyte, inorganic salts, also is not subject to the influence of soda acid, and good with the compatibility of other surfactants, and haemolysis is less.In theory; The HLB value that the preparation of O/W type nanometer emulsion needs surfactant is between 8～18; Consider preparation technology's simplicity; Be the easy formation property of nano-emulsion and the stability of the nano-emulsion for preparing, the present invention selects the liquid nonionic surfactant of HLB between 10～15 for use.The preferred tween 80 that uses.
The present invention with Rue oil., Oleum Viticis Negundo, Oleum Bupleuri, perilla oil, garlicin and fumaric acid tiamulin as combination; Be because Rue oil. contains piperitone 40～50%, carene-4 20%, Mang geraniol 10%, Mang Ethylgeranate 10%, Mang geranial, limonene etc. are still arranged.Clinical practice proves, Rue oil. has significant cough-relieving, relievings asthma, relieve chronic tracheitis and SOA and have certain antibacterial action.Mainly contain dosage form such as Rue oil. drop pill on the market and be used for treating chronic tracheitis and asthma, curative effect is obvious, and the piperitone that its effect contains with it, carene-4 etc. have much relations; Oleum Viticis Negundo includes β-Flos Caryophylli alkene, can obviously promote IgG content in the serum, strengthens humoral immunization and macrophage phagocytic power, and the infection effect is remarkable; That Oleum Bupleuri has is analgesic, analgesia and antiinflammatory action, the fervescence that the poultry concurrent infection is caused, and inflammatory reaction such as myalgia have significant therapeutic effect, and can effectively improve clinical symptoms and shorten the course of disease; Perilla oil has the sending down the abnormal ascending QI expectorant, relievings asthma, and the effect of lung moistening is used for expectorant and stops up the QI rising in reverse order, and cough and asthma plays synergism with Rue oil., plays the effect of auxiliary treatment; Garlicin has stronger antibacterial and anti-inflammation functions; Thereby the oxygen atom in its molecule is bred growth and the breeding that the sulfydryl in the necessary cysteine molecule combines and suppressed antibacterial with bacterial growth; Multiple coccus, bacillus, fungus, virus etc. all there are inhibition and killing action; Can prevent and treat the infection of other pathogen that poultry merge during one's sickness, healthy poultry are also had health-care effect; Fumaric acid tiamulin has another name called Tiamulin; Gram positive bacteria (like golden Portugal bacterium, streptococcus), mycoplasma (chicken virus mycoplasma, mycoplasma hyopneumoniae), actinobacillus pleuropneumoniae and pig treponema etc. all there are stronger antibacterial action, are used for treatment chronic respiratory disease, swine enzootic pneumonia, contagious pleuropneumonia etc.Synergism is played in each medicine combination back of distinguishing the flavor of, and effect strengthens.
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 nano emulsion composition through the lasting clear of check outward appearance, is not found breakdown of emulsion situation such as muddiness or deposition behind storage under the room temperature nature change condition, explain that ageing stability is good.
2, heat storage stability
This nano emulsion composition is sub-packed in several vials, places 50 ℃ of calorstats to store 15d after the sealing, the every sampling at a distance from 5d observed.The result shows that this nano-emulsion heat storage back check outward appearance still keeps the outward appearance of clear, does not find breakdown of emulsion situation such as muddiness or layering, explains that heat storage stability is good.
3, anti-freeze-stable property
With this nano emulsion composition in refrigerator-10 ℃ preserve a week after.Return to room temperature.This nano-emulsion can be liquid by solid-state thawing, and outward appearance clear is still placed all continued and checked after the dilution check, does not find breakdown of emulsion situation such as muddiness or deposition, shows that freezing-resistance is good.
4, accelerated stability
This nano emulsion composition is placed test tube, sealing, under the rotating speed of 15000r/min centrifugal 20 minutes, outward appearance clear was not still found breakdown of emulsion situation such as muddiness or deposition after dilution is checked.
5, light stability experiment
This nano emulsion composition of part is loaded in the vial, and sealing places under the daylight, and light at room temperature is taken a sample respectively in 1d, 3d, 5d, 10d according to 10d.Keep clear through this nanoemulsions of dilution inspection show, breakdown of emulsion situation such as no muddiness or layering show that light stability is good.
A kind of oil-in-water type nano emulsion composition that is used for the treatment of livestock and poultry mycoplasma pneumonia of the present invention has the effect of respiratory system diseases such as treatment fowl chronic respiratory tract disease, mycoplasma pneumoniae of swine and contagious pleuropneumonia.
Usage and dosage: oral or drinking-water.This nanoemulsions of water dilution per ton, pig 5L; Fowl 10L.Freely drink logotype 4～5 days.
A kind of oil-in-water type nano emulsion composition that is used for livestock and poultry mycoplasma pneumonia treatment 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, be used to prevent and treat livestock and birds respiratory disease;
2) thermodynamic stability is high.This nano emulsion composition stores not phase-splitting, does not precipitate between-10 ℃ and 50 ℃, not muddy, the breakdown of emulsion situation do not occur, and stability improves;
3) absorbance is higher than the market general formulation.This nano emulsion composition emulsion droplet particle diameter can be better by intestinal absorption after oral between 1 ~ 100nm, and absorbance is higher than drop pill etc.;
4) after intestinal absorption, can avoid the first pass effect of liver, bioavailability of medicament is improved;
5) method technology is simple, is fit to large-scale production.
The specific embodiment
Below come the further beneficial effect of elaboration medicine according to the invention through drug safety test with the comparative efficacy test.
Test Example 1Nano emulsion composition medicine of the present invention (is example with embodiment 1) safety testing
The health-care eggs chickling at 60 one monthly ages is divided into blank group and 2 groups of this nano emulsion composition (is example with embodiment 2) groups, 30 every group at random.Every of this nano emulsion composition group is irritated this nanoemulsions of stomach 1.0ml, and every of blank group is irritated stomach equivalent normal saline, once a day, and one week of continuous irrigation stomach.Observe chicken crowd's active situation and health status during this time every day, and keep a record; Behind the last administration 6h, chicken is put to death and cuts open inspection, observe the pathological change of each internal organs, and keep a record.
The result shows: two groups of chicken crowd active situation and health status are all normal, cut open the also no abnormal pathological changes of inspection each internal organs of back, and zero difference between two groups shows that this nanoemulsions safety is good.
Test Example 2Nano emulsion composition of the present invention and the test of other preparation for treating chronic respiratory disease effect comparison
, the natural infection chicken chooses 60 of the sick chickling of approximate occurring degree from relieving internal heat mycoplasma morbidity chicken crowd; It is divided into three groups of blank group, doxycycline group and this nano emulsion composition groups at random; Alternative get healthy with age in days with 20 of kind chickling as negative control group; 4 groups of chicken crowds raise down in the same terms, but isolate each other.Negative control group and blank group chicken crowd drink the cleaning tap water every day, and the doxycycline group is pressed the metering of 100mg/L and freely drunk water, and this nano emulsion composition (is example with embodiment 1) group supplies it freely to drink by the metering dilution back of 10g/L water.Other similar medicines of forbidding were treated 3 days continuously during the medication, observed chicken crowd activity situation and record every day.
Curative effect judging standard:
Invalid: suffer from chicken and still show rhinorrhea, cough has the hello sound during breathing, lethargy, and two wings are sagging, are reluctant to take food and walk about, and serious before treating;
Effectively: suffer from the chicken respiratory symptom and alleviate to some extent before the treatment, the hello sound is faint during breathing, and diet recovers gradually, and spirit and activity make moderate progress;
Produce effects: suffer from the chicken respiratory transference cure, air communication is smooth during breathing, and the hello sound disappears, and diet, activity and spirit are basic to be recovered, and performance is active;
Cure: suffer from chicken diet situation and active situation and healthy chicken indifference, the symptom complete obiteration;
Table 1This nano emulsion composition and doxycycline treatment chronic respiratory disease effect comparison result of the test
Can be known by table 1: blank group cure rate is 0, and obvious effective rate is 0, and effective percentage is 5%, and inefficiency is 95%, always effectively is 5%; Doxycycline group cure rate is 35%, and obvious effective rate is 25%, and effective percentage is 15%, and inefficiency is 25%, and total effective rate is 75%; This nano emulsion composition group cure rate is 60%, and obvious effective rate is 25%, and effective percentage is 10%, and inefficiency is 5%, and total effective rate is 95%.
Can be found out by the result: a kind of nano emulsion composition treatment mycoplasma gallinarum infectious effect that is used for the treatment of livestock and poultry mycoplasma pneumonia of the present invention is better than doxycycline.
Below come further to set forth medicine according to the invention through specific embodiment composition and method for preparing.
Embodiment 1
Rue oil. 3.0g, Oleum Viticis Negundo 1.9g, perilla oil 0.8g, Oleum Bupleuri 1.2g, garlicin 0.1g, fumaric acid tiamulin 3.0g, tween 80 27.0g, distilled water 63.0g.
Above-mentioned each component is processed the nano emulsion composition that is used for the treatment of livestock and poultry mycoplasma pneumonia, comprises the following steps:
1) accurately take by weighing the quality of tween 80, Rue oil., Oleum Viticis Negundo, perilla oil, Oleum Bupleuri, garlicin, fumaric acid tiamulin, distilled water by filling a prescription, subsequent use;
2) with Rue oil., Oleum Viticis Negundo, perilla oil, Oleum Bupleuri, the garlicin mixing and stirring of said amount, as oil phase;
3) join the surfactant tween 80 of said amount in the middle of the oil phase and stir;
4) fumaric acid tiamulin of said amount is dissolved in the distilled water of said amount and with its aqueous solution as water; At room temperature stir oil phase and tween 80 mixture rapidly; Slowly drip water when stirring, this mixture system can occur by rare retrogradation, and is last again by thick thinning a series of variations; Be transparent liquid until system, promptly get this nano emulsion composition.
Embodiment 2
Rue oil. 8.0g, Oleum Viticis Negundo 1.0g, perilla oil 0.1g, Oleum Bupleuri 0.2g, garlicin 0.05g, fumaric acid tiamulin 2.5g, tween 80 28.0g, distilled water 61.05g.
Embodiment 3
Rue oil. 2.0g, Oleum Viticis Negundo 5.0g, perilla oil 0.2g, Oleum Bupleuri 0.1g, garlicin 0.05g, fumaric acid tiamulin 2.8g, tween 80 26.0g, distilled water 63.85g.
Embodiment 4
Rue oil. 4.3g, Oleum Viticis Negundo 2.9g, perilla oil 3.0g, Oleum Bupleuri 0.9g, garlicin 0.08g, fumaric acid tiamulin 3.5g, tween 80 22.8g, distilled water 62.52g.
Embodiment 5
Rue oil. 3.3g, Oleum Viticis Negundo 2.0g, perilla oil 0.1g, Oleum Bupleuri 2.0g, garlicin 0.1g, fumaric acid tiamulin 2.0g, tween 80 30.0g, distilled water 60.5g.
Embodiment 6
Rue oil. 4.5g, Oleum Viticis Negundo 1.0g, perilla oil 1.0g, Oleum Bupleuri 0.2g, garlicin 0.05g, fumaric acid tiamulin 1.0g, tween 80 25.0g, distilled water 67.25g.
Embodiment 7
Rue oil. 3.8g, Oleum Viticis Negundo 0.5g, perilla oil 0.5g, Oleum Bupleuri 0.5g, garlicin 0.06g, fumaric acid tiamulin 2.0g, tween 80 19.0g, distilled water 73.64g.
Embodiment 8
Rue oil. 4.0g, Oleum Viticis Negundo 1.0g, perilla oil 0.5g, Oleum Bupleuri 0.3g, garlicin 0.01g, fumaric acid tiamulin 4.0g, tween 80 23.0g, distilled water 67.19g.
Embodiment 9
Rue oil. 5.0g, Oleum Viticis Negundo 2.0g, perilla oil 0.5g, Oleum Bupleuri 0.2g, garlicin 0.1g, fumaric acid tiamulin 0.1g, tween 80 31.0g, distilled water 61.1g.
Embodiment 10
Rue oil. 0.1g, Oleum Viticis Negundo 1.5g, perilla oil 1.0g, Oleum Bupleuri 1.0g, garlicin 0.05g, fumaric acid tiamulin 3.0g, tween 80 29.0g, distilled water 64.35g.
Claims (3)
1. an oil-in-water type nano emulsion composition that is used for the treatment of livestock and poultry mycoplasma pneumonia is characterized in that, is made up of following raw materials by weight percentage:
Rue oil. 0.1%～8.0%, Oleum Viticis Negundo 0.1%～5.0%, perilla oil 0.1%～3.0%, Oleum Bupleuri 0.1%～2.0%, garlicin 0.01%～0.1%, fumaric acid tiamulin 0.1%～4.0%, surfactant 19.0%～31.0%, surplus are distilled water, and the mass percent sum of above-mentioned raw materials is 100%;
Described glass or plastic containers tween 80.
2. a kind of oil-in-water type nano emulsion composition that is used for the treatment of livestock and poultry mycoplasma pneumonia according to claim 1, it is characterized in that: the particle diameter of this nano-emulsion is between 1～100nm.
3. a kind of oil-in-water type nano emulsion composition method for preparing that is used for the treatment of livestock and poultry mycoplasma pneumonia according to claim 1 is characterized in that, may further comprise the steps:
Accurately take by weighing the quality of surfactant, Rue oil., Oleum Viticis Negundo, perilla oil, Oleum Bupleuri, garlicin, fumaric acid tiamulin, distilled water by filling a prescription, subsequent use;
With Rue oil., Oleum Viticis Negundo, perilla oil, Oleum Bupleuri, the garlicin mixing and stirring of said amount, as oil phase;
The surfactant of said amount is joined in the middle of the oil phase and stirs;
With the fumaric acid tiamulin of said amount be dissolved in the distilled water of said amount and with its aqueous solution as water; At room temperature stir oil phase and surfactant mixture rapidly; Slowly drip water when stirring; Be transparent liquid until system, promptly get the oil-in-water type nano emulsion composition that is used for the treatment of livestock and poultry mycoplasma pneumonia.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102895377A (en) * | 2012-11-09 | 2013-01-30 | 挑战（天津）动物药业有限公司 | Pharmaceutical composition for treating livestock respiratory diseases and method for preparing pharmaceutical composition for treating livestock respiratory diseases |
| CN103623313B (en) * | 2013-12-03 | 2015-10-21 | 金陵科技学院 | Traditional Chinese medicine composition for preventing and treating swine mycoplasmal pneumonia and preparation method and application thereof |
| CN105902639A (en) * | 2016-06-16 | 2016-08-31 | 福建傲农生物科技集团股份有限公司 | Pharmaceutical preparation for prevention and treatment of chronic respiratory diseases of livestock and poultry and preparation method thereof |
| CN106727351A (en) * | 2016-12-28 | 2017-05-31 | 重庆金邦动物药业有限公司 | Amoxicillin micro-capsule dry suspensoid agent and preparation method thereof |
-
2012
- 2012-03-07 CN CN2012100572660A patent/CN102600304A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102895377A (en) * | 2012-11-09 | 2013-01-30 | 挑战（天津）动物药业有限公司 | Pharmaceutical composition for treating livestock respiratory diseases and method for preparing pharmaceutical composition for treating livestock respiratory diseases |
| CN102895377B (en) * | 2012-11-09 | 2015-03-11 | 挑战（天津）动物药业有限公司 | Pharmaceutical composition for treating livestock respiratory diseases and method for preparing pharmaceutical composition for treating livestock respiratory diseases |
| CN103623313B (en) * | 2013-12-03 | 2015-10-21 | 金陵科技学院 | Traditional Chinese medicine composition for preventing and treating swine mycoplasmal pneumonia and preparation method and application thereof |
| CN105902639A (en) * | 2016-06-16 | 2016-08-31 | 福建傲农生物科技集团股份有限公司 | Pharmaceutical preparation for prevention and treatment of chronic respiratory diseases of livestock and poultry and preparation method thereof |
| CN106727351A (en) * | 2016-12-28 | 2017-05-31 | 重庆金邦动物药业有限公司 | Amoxicillin micro-capsule dry suspensoid agent and preparation method thereof |
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Application publication date: 20120725 |