CN102293764B - New application of p-hydroxycinnamic acid - Google Patents
New application of p-hydroxycinnamic acid Download PDFInfo
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Abstract
The invention discloses new application of p-hydroxycinnamic acid to preparation of medicines for preventing and treating viral disease or bacterial disease of livestock and poultry. The product can prevent and treat viral disease or bacterial disease of livestock and poultry and can improve production performance of livestock and poultry. In vivo and in vitro tests show that the p-hydroxycinnamic acid can prevent and treat diseases caused by mycoplasma gallisepticum, bovine colibacillosis and the like. The in vivo test shows that the p-hydroxycinnamic acid can prevent and treat poultry bursa fabricius viral disease, avian mycoplasmosis and bird flu H9 and H5 subtype virus infection.
Description
The application is to be on 02 08th, 2010 the applying date, and application number is 201010109913.9 divides an application.
Technical field
The present invention relates to the new purposes of p-Coumaric Acid, be specifically related to application, particularly livestock and poultry virus or the bacterial bursal disease, avian influenza, chronic respiratory tract disease of p-Coumaric Acid in preparation control livestock and poultry viral disease, bacterial disease medicine.
Background technology
In recent years, more and more be subject to consumers in general's common concern along with the safety problem of livestock products, the production of publicly harmless animal product has become the inexorable trend of animal husbandry development.Developed country is increasingly strict with management for the veterinary drug registration, and European Union announced once that antibiotic in 2006 was not re-used as the additive that promotes production and uses, and had forbidden many medicines for animals.A few class green additives such as enzyme preparation, probiotics, Chinese herbal medicine become veterinary drug manufacturing enterprise outline thereupon.Especially residual new veterinary drugs low, that toxic and side effects is little is taken the course of its own in numerous veterinary drug products, has wide market prospect.
Ministry of Agriculture's dispatch in 2005 provides against the broad-spectrum medicinal (moroxydine, amantadine, rimantadine, Acyclovir) that the mankind are used and is applied in the poultry medicine, prevent that the antiviral drugs drug resistance from transmitting to the mankind from poultry, but, some infectious disease of China still lacks effective vaccine and controls (as breathing breeding syndrome, porcine myocarditis, porcine nameless high-fever etc.), prevents these diseases therefore be badly in need of developing active drug.In addition, in Production of Livestock and Poultry, bird flu, mycoplasma, escherichia coli etc. are widely current, these bacterial diseases of current control mainly rely on antibiotic therapy, abuse, drug resistance appearance due to antibiotics, cause bacterial infectious disease prevention and treatment difficulty to strengthen, drug residue is also threatening human food's safety and healthy simultaneously.
P-Coumaric Acid has another name called P-coumaric acid, by hydroxy benzaldehyde and malonic acid effect and get.P-Coumaric Acid is now multiplex in spice or as the acidulant of beverage, also can be used as the antioxidant of oils and fats.In medical industry, it is the raw material of many pharmaceuticals, as synthetic antiadrenergic drug esmolol.In addition, p-Coumaric Acid is also made acidulant and medically as multivalent intercalating agent, is also chemical intermediate in medicine, as being used for the synthetic of new drug farrerol of eliminating the phlegm; As the satisfying fixed intermediate of production therapeutic drug of coronary heart disease, and for the manufacture of local anesthetic, antibacterial and hemorrhage etc.; It also has the effect of cervical cancer inhibiting.Agriculturally, for the production of plant growth promoter, long-acting fungicide and preserving fruit and vegetable utilizing antiseptic.Aspect chemical industry, p-Coumaric Acid is very important essence and flavoring agent, is mainly used in configuring the spice such as fragrant hot Fructus Pruni pseudocerasi, Fructus Pruni, Mel.Be used for preparation fancy soap and cosmetic essence in the daily use chemicals industry.Aspect cosmetics, p-Coumaric Acid all has inhibitory action to tryrosinase list phenolase and two phenolase activity, causes single phenolase vigor and diphenol enzyme activity to descend 50%, is used in the generation of cosmetics the insides check melanin.
In addition, p-Coumaric Acid or a kind of potent conductive material, Recent study is extensive in liquid crystal display industry.Graft reaction by hydroxyl polyimides and p-Coumaric Acid synthesized have heliosensitivity to the hydroxyl polyimides, and determined the structure of heliosensitivity to the hydroxyl polyimides by infrared, nuclear-magnetism.With the synthetic hydroxyl polyimides is used in liquid crystal display device as liquid crystal aligning layer, prove good heat stability.In recent years, the lot of domestic and international scientist also is devoted to p-Coumaric Acid research is expanded to microorganism and medical domain---the impact of cell differentiation and telomerase activation.
Have no at present the report that relevant p-Coumaric Acid medicine is used for anti-livestock and poultry viruses or bacteria resistance disease.
Summary of the invention
The object of the invention is to provide the new purposes of p-Coumaric Acid, i.e. application in preparation control livestock and poultry viral disease, bacterial disease medicine.
The inventor studies and finds that the Chinese medicine Fructus Mume extract has antibiotic, antiviral activity composition, and laboratory proofing also confirms to have good preventive values.By external and in vivo test, follow the trail of active site, use the materials such as silica gel, Sephadex LH-20 gel by modern chromatographic process, separate obtaining monomeric compound from Fructus Mume, utilize Modern spectroscopy technology etc. to parse monomer structure (Chinese: p-Coumaric Acid; English name: 4-hydroxylcinnamic acid).
The inventor has passed through a large amount of laboratorys and clinical verification, find that p-Coumaric Acid has antiviral activity and wide spectrum antibacterial activity, effectively prevent and treat avian escherichia coli, chicken virus mycoplasma etc., can partly substitute antibiotic therapy poultry intractable respiratory tract disease, thereby reduction sickness rate, effectively improve survival rate and the rate of body weight gain of poultry, improve the production capacity of poultry.
More particularly, p-Coumaric Acid has the effect that suppresses poultry bursal disease virus, bird flu H9 hypotype, can effectively kill the pathogenic bacterium that cause the animal morbidity simultaneously, such as: the antibacterials such as chicken colibacillosis, chicken virus mycoplasma.
The present invention estimates p-Coumaric Acid antiviral and antibiotic effect, finds that it can effectively suppress chicken colibacillosis and chicken virus mycoplasma.In vivo test shows: according to 25 mg/kgs of body weight, continuous oral is after 5 days, and p-Coumaric Acid is highly resistant to the attack of bursal disease virus, reduces mortality rate, also has the effect of control coli-infection simultaneously.
Based on this, the present invention proposes the application of p-Coumaric Acid in preparation prevention and treatment livestock and poultry viral disease or bacterial disease medicine.
Above-mentioned livestock and poultry viral disease includes but not limited to the virosis that bursal disease virus, low pathogenicity bird flu H9 hypotype, high pathogenic avian influenza H5 subtype virus cause.The virosis that for example bursal disease virus IBDV LX strain, bird flu virus H9N2 strain, H5N1 strain cause.
Above-mentioned bacterial disease includes but not limited to the bacterial disease that chicken colibacillosis, chicken virus mycoplasma cause.
The present invention further provides a kind of poultry medicine that contains the effective dose p-Coumaric Acid.Can add pharmaceutic adjuvant to be prepared into various dosage forms according to the conventional formulation method of this area, for example, can be powder, tablet, granule, oral liquid etc., is preferably oral liquid.The p-Coumaric Acid medicine is pressed 10-40 mg/kg of body weight, can pass through oral administration.
In addition, can also be with p-Coumaric Acid and other active ingredient administering drug combinations.
The present invention has following beneficial effect:
P-Coumaric Acid can be widely used in aviculture, pig industry, part substitutes antiviral drugs and antibiotics, make up the bad loss that causes of the present vaccine prevention effect of China, substitute drug resistance antibiotics control poultry bacterial disease, popular and the solution food antibiotics of control infectious disease is residual, the assurance food safety, improves the competitiveness that animal product exports.
The specific embodiment
Following examples further illustrate content of the present invention, but should not be construed as limitation of the present invention.Without departing from the spirit and substance of the case in the present invention, modification or replacement to the inventive method, step or condition are done all belong to scope of the present invention.
If do not specialize, the conventional means that in embodiment, technological means used is well known to those skilled in the art.
The percentage sign that relates in the present invention " % " if do not specify, refers to mass percent; But the percentage ratio of solution except as otherwise herein provided, refers to contain in solution 100ml the some grams of solute; Percentage ratio between liquid refers to the ratio of capacity in the time of 20 ℃.
P-Coumaric Acid far becomes Science and Technology Ltd. available from Wuhan, Hubei.
Embodiment 1
P-Coumaric Acid content of the present invention: p-Coumaric Acid 25mg/ml.Its preparation process is as follows:
Weigh by above-mentioned weight portion, after fully dissolving with 30% dehydrated alcohol, add 20% tween 20 and 50% water, mix homogeneously is distributed into bottle, gets oral liquid formulations.
Embodiment 2
P-Coumaric Acid content of the present invention: p-Coumaric Acid 20mg/ml.Its preparation process is as follows:
Weigh by above-mentioned weight portion, after fully dissolving with 30% dehydrated alcohol, add 20% tween 20 and 50% water, mix homogeneously is distributed into bottle, gets oral liquid formulations.
Embodiment 3
P-Coumaric Acid content of the present invention: p-Coumaric Acid 35mg/ml.Its preparation process is as follows:
Weigh by above-mentioned weight portion, after fully dissolving with 30% dehydrated alcohol, add 20% tween 20 and 50% water, mix homogeneously is distributed into bottle, gets oral liquid formulations.
Embodiment 4
P-Coumaric Acid content of the present invention: p-Coumaric Acid 40mg/ml.Its preparation process is as follows:
Weigh by above-mentioned weight portion, after fully dissolving with 30% dehydrated alcohol, add 20% tween 20 and 50% water, mix homogeneously is distributed into bottle, gets oral liquid formulations.
Embodiment 5
P-Coumaric Acid content of the present invention: p-Coumaric Acid 15mg/ml.Its preparation process is as follows:
Weigh by above-mentioned weight portion, after fully dissolving with 30% dehydrated alcohol, add 20% tween 20 and 50% water, mix homogeneously is distributed into bottle, gets oral liquid formulations.
As special instruction, the p-Coumaric Acid that following experimental example is mentioned are not arranged is the p-Coumaric Acid preparation of embodiment 1 gained.
Experimental example 1 p-Coumaric Acid is to cattle escherichia coli, the test of avian escherichia coli In Vitro Bacteriostasis
Use the sterile saline p-Coumaric Acid preparation that embodiment 1 is prepared to be mixed with the 25mg/ml medicinal liquid standby.
Minimal inhibitory concentration (MIC) is measured: determine that by the test tube coubling dilution compound recipe is to the minimal inhibitory concentration (MIC) of broiler escherichia coli separated strain.Get 10 sterilizing test tubes, be numbered 1#, 2#, 3#, 4#, 5#, 6#, 7#, 8#, antibacterial contrast and meat soup contrast.Respectively add sterilization meat soup 1ml in 10 test tubes.Add sterilization medicinal liquid 1ml in the 1# test tube, after mixing, get 1ml and put to the 2# test tube, doubling dilution, to the 8# test tube, discard 1ml successively, and control tube does not add medicinal liquid.Except the meat soup contrast, all the other each Guan Jun add escherichia coli 1ml.Test tube is put on 37 ℃ of constant-temperature tables cultivated 24h, the 2nd day observed result.For eliminating the impact of medicine itself, can not be connected on nutrient agar plate medium by completely specified test tube liquid rotating, cultivate 24h for 37 ℃.Observe next day and have or not bacterial growth in plate.Should test and repeat 3 times, observe its repeatability and stability, eliminate occasionality.
Table 1 p-Coumaric Acid preparation killing in vitro antibacterial minimal effective concentration
The cattle escherichia coli are one of the main pathogenic fungi that cause bacillary mastitis, and the p-Coumaric Acid preparation is 15mg/ml to the colibacillary minimal inhibitory concentration of cattle, and the prompting p-Coumaric Acid has potential using value to the bacillary mastitis for the treatment of cattle; And p-Coumaric Acid the minimum of avian escherichia coli is pressed down concentration is 0.8mg/ml, be research p-Coumaric Acid antibacterial activity, further verify with in vivo test.
The therapeutic test of experimental example 2. p-Coumaric Acids to chicken colibacillosis
The 21 blue brown chickens in age in days sea are divided into 6 groups at random, be respectively the high, medium and low dosage group of p-Coumaric Acid group, advantage (20% composite sulfamonomethoxine soluble powder of sodium, Sichuan Bayer animal health company limited is produced, lot number 2008102409) positive controls, negative control group, the blank group.(median lethal dose(LD 50) is 4 * 10 to lumbar injection escherichia coli clinical separation strain
8CFU), 0.5ml/, administration in 12 hours after counteracting toxic substances, oral administration gavage shown according to the form below 2.Successive administration 7 days, minute twice administration of upper and lower noon, drug withdrawal is observed after 3 days and is cutd open inspection.
Table 2 test grouping and administration situation
| Grouping | Quantity | Dosage | Administration number of times |
| High dose group (35mg/ml) | 10 | The 35mg/kg body weight | 2 times/days |
| Middle dosage group (25mg/ml) | 10 | The 25mg/kg body weight | 2 times/days |
| Low dose group (15mg/ml) | 10 | The 15mg/kg body weight | 2 times/days |
| Positive controls favourable | 10 | The 15mg/kg body weight | 2 times/days |
| Negative control group | 10 | - | 1 times/day |
| The normal healthy controls group | 10 | - | 1 times/day |
Observation index:
Mortality rate: all at duration of test, escherichia coli disease symptoms and dead appears, and cuing open inspection rear gasbag, liver, heart has the typical cytopathic feature, and pathological material of disease can be isolated colibacillary, is judged as to infect deadly, calculates mortality rate.
The relative weight gain rate: the body weight of every chicken during according to on-test and end, calculate the average weight gain of weightening finish and every group of chicken, and take the weightening finish of normal healthy controls group as 100%, respectively organize weightening finish and obtain by comparison respectively organizing the relative weight gain rate.
Cut open inspection survival chicken after experiment finishes, observe the situations such as pericarditis, perihepatitis, and get liver, the aseptic rear separation and Culture antibacterial of drawing materials, statistics liver escherichia coli recall rate situation.
Experimental result is as follows: table 3.
The impact of table 3 on meat chicken production performance
Annotate: the relative weight gain rate: the body weight of every chicken during according to on-test and end, calculate the average weight gain of weightening finish and every group of chicken, and increase weight as 100% take the blank group, each is organized weightening finish and obtains by comparison respectively organizing the relative weight gain rate.
A-BBe not all significant difference (P＜0.05) with letter sign in string;
A-CBe not all difference extremely significantly (P＜0.01) with letter sign in string.
Aspect survival rate, the high, medium and low dosage group of p-Coumaric Acid is respectively 70.0%, 80.0% and 60.0%, and matched group favourable reaches 80%, and statistical analysis finds that in cinnamic acid, dosage group, high dose and matched group difference favourable are not remarkable.
In the relative weight gain rate, p-Coumaric Acid is high, in and low dose group be respectively 88.8%, 95.9%, 66.7%, opposite matched group favourable is 88.3%, through significance analysis, middle dosage group and matched group significant difference favourable (P＜0.05).
Experimental example 3 p-Coumaric Acid prevention infectious bursal diseases and the test of medication amount effect relationship
Select the sea blue brown chickling of 21 ages in days, with the p-Coumaric Acid group (35 mg/kgs of body weight) of embodiment 3,1,5 gained, p-Coumaric Acid group (25 mg/kgs of body weight), p-Coumaric Acid group (15 mg/kgs of body weight), high immunity yolk antibody (available from Luoyang Pulaike Biological Engineering Co., Ltd., lot number 080324) matched group, viral dilution liquid group (positive controls), blank group (negative control group), every group 8, totally 48 chickens, the grouping situation is as shown in table 2.Take IBDV LX strain as counteracting toxic substances strain, 100ID
50/ 0.2ml is by eye dripping, collunarium approach.Except the blank group, other respectively organizes equal counteracting toxic substances, every chicken eye dripping 0.2ml, and administration is counteracting toxic substances after three days.Medication group successive administration 7 days, every day is administration at twice, high immunity yolk antibody matched group: 0.5ml/ chicken muscle injection, continuous two days; Give observation post administration and cutd open inspection in 2 days.The mental status of duration of test viewing test group and matched group, feed intake, diarrhoea situation, the dead quantity of chicken etc.Cut open check weighing point and observe the pathological changes situation of fabricius bursa, whether whether enlargement or atrophy, hemorrhage, surface have the gel-shaped exudate.Observe chest muscle and whether lower limb myopathy varying index is hemorrhage, extent of hemorrhage, measure the pathological changes index, result is as shown in following table 4-table 8.
Grouping and the processing of table 4 prophylactic tria chicken
Body weight change situation during table 5 p-Coumaric Acid prevention fabricius bursa infects
From body weight change, three groups of the relative weight gain rates of p-Coumaric Acid present regular the variation, and high, medium and low dosage is respectively 56.651%, 56.65% and 47.78%, and high, middle dosage group is compared with low dose group, significant difference is with infection matched group difference and remarkable.
Table 6 p-Coumaric Acid prevention fabricius bursa result of the test
The survival rate that infects matched group, high immunity yolk antibody group is 50.5%, 100%.Each dosage group survival rate of p-Coumaric Acid is respectively 81.8%, 62.5% and 42.86%, is certain regularity and changes.
Each organ disease integration situation of table 7
Fabricius bursa pathological changes integration: fabricius bursa is hemorrhage, ooze out the ratio that adds up to total points and this group experimental animal number; Breast lower limb myopathy becomes integration: the hemorrhage total total points of breast leg muscle is organized the ratio of experimental animal number with this;
The nephropathy integration: pathological changes adds up to total points and this to organize the ratio of experimental animal number; Pathological changes adds up to total points and this to organize the ratio of experimental animal number; Pathological changes integration slip: (infecting matched group pathological changes integration-test group pathological changes integration)/infection matched group pathological changes integration
Annotate: the bursal disease varying index is determined as follows: severe haemorrhage 4 minutes; Moderate 3 minutes; Slight 1 minute; Chest muscle and lower limb myopathy varying index: 3 minutes/side of severe haemorrhage, the hemorrhage 2 minutes/side of moderate, 1 minute/side of hyporrhea
From cuing open the inspection situation, in p-Coumaric Acid, the pathological changes integration slip of dosage group is up to 90%, the high and low dose group is 70%, the equal significance of pathological changes slip of three dosage groups can judge thus that higher than high immunity yolk antibody group 40% p-Coumaric Acid has preventive effect preferably for infectious bursal disease.
The Immune Organs Index of table 8 prevention experiment is measured
By upper table relative immunity organ index as can be known: each dosage group fabricius bursa index of p-Coumaric Acid is all lower than infecting matched group, and index and spleen index is all higher than the high immunity yolk antibody group, and this shows that medicine has positive effect to the raising of chicken cell immunity and immunity system function.
In sum, p-Coumaric Acid has for a prevention poultry infectious bursal disease effect that improves rate of body weight gain, reduces sickness rate and improve immunity of organisms.
Experimental example 4 p-Coumaric Acid treatment infectious bursal diseases and the test of medication amount effect relationship
Select the sea blue brown chickling of 21 ages in days, p-Coumaric Acid group (35 mg/kgs of body weight), p-Coumaric Acid group (25 mg/kgs of body weight), p-Coumaric Acid group (15 mg/kgs of body weight), astragalus polysaccharides (available from the auspicious high animal pharmaceutical estate company limited lot number 09100701 in Hebei) matched group (250 mg/kgs of body weight), viral dilution liquid group (positive controls), blank group (negative control group) with embodiment 3,1,5 gained, every group 8, totally 48 chickens, the grouping situation is as shown in table 9.With the strain of IBDV LX strain counteracting toxic substances, 100ID
50/ 0.2ml is by eye dripping, collunarium approach.Except the blank group, other respectively organizes equal counteracting toxic substances, every chicken eye dripping, collunarium 0.2ml, administration after counteracting toxic substances.Medication group successive administration 5 days, every day is administration at twice, gives observation post administration and cuts open inspection in 2 days.The mental status of duration of test viewing test group and matched group, feed intake, diarrhoea situation, the dead quantity of chicken etc.Cut open check weighing point and observe the pathological changes situation of fabricius bursa, whether whether enlargement or atrophy, hemorrhage, surface have the gel-shaped exudate.Observe chest muscle and whether lower limb myopathy varying index is hemorrhage, extent of hemorrhage, measure the pathological changes index, result is as shown in the table.
Grouping and the processing of table 9 therapeutic test chicken
Body weight change situation during table 10 p-Coumaric Acid treatment fabricius bursa infects
From body weight change, the weightening finish of three groups of p-Coumaric Acids presents regular the variation, high dose group, in, the low dosage rate of body weight gain is respectively 78.4%, 72.0% and 71.2%.The astragalus polysaccharides matched group is 80.6%.80 (table 10).
Table 11 p-Coumaric Acid treatment fabricius bursa result of the test
The survival rate that infects matched group, astragalus polysaccharides group is 40.0% and 70.0%.Each dosage group of p-Coumaric Acid is respectively 90.0%, 80.0% and 60.0%, be certain regularity and change, compare with the astragalus polysaccharides matched group, high dose group significant difference (P＜0.05), middle dosage group and low dose group difference be remarkable (table 11) not.
Each organ disease integration situation of table 12
Annotate: fabricius bursa pathological changes integration: fabricius bursa is hemorrhage, ooze out the ratio that adds up to total points and this group experimental animal number; Breast lower limb myopathy becomes integration: the hemorrhage total total points of breast leg muscle is organized the ratio of experimental animal number with this;
Pathological changes integration slip: (infecting matched group pathological changes integration-test group pathological changes integration)/infection matched group pathological changes integration.
Annotate: the bursal disease varying index is determined as follows: severe haemorrhage 4 minutes; Moderate 3 minutes; Slight 1 minute; Chest muscle and lower limb myopathy varying index: 3 minutes/side of severe haemorrhage, the hemorrhage 2 minutes/side of moderate, 1 minute/side of hyporrhea.
From cuing open the inspection situation, p-Coumaric Acid is high, the pathological changes integration slip of middle dosage group is up to 87.5%, all higher than astragalus polysaccharides group 50%, and significant difference (P＜0.05).Can judge thus that p-Coumaric Acid has for infectious bursal disease and protect preferably effect.
Table 13 Immune Organs Index
A-BBe not all significant difference (P＜0.05) with letter sign in string;
A-CBe not all difference extremely significantly (P＜0.01) with letter sign in string.
By upper table relative immunity organ index as can be known: each dosage group fabricius bursa index of p-Coumaric Acid is all lower than infecting matched group, and index and spleen index is also lower than infecting matched group and astragalus polysaccharides matched group (table 13), and this shows that medicine has positive effect to the raising of chicken cell immunity and immunity system function.
In sum, p-Coumaric Acid has for a treatment poultry infectious bursal disease effect that improves rate of body weight gain, reduces sickness rate and improve immunity of organisms.
The experimental example 5 sick tests of p-Coumaric Acid treatment chicken virus mycoplasma
1 experimental technique
1 aa broiler chicken is used for this test, raises counteracting toxic substances chicken virus mycoplasma HS strain during 7 age in days under normally raising condition.(measuring culture contains bacteria concentration and is about 10 to use 24h to reach the logarithmic growth peak period in can liquid medium within
8CCU/ml) 3 generation HS strain cultures, through eye dripping, collunarium and the trachea injection inoculation AA type broiler in 7 age in days health, 0.5ml/ only, after the chicken group approximately has the half morbidity, begin dispensing after 16d, each organizes chicken respectively by administration shown in table 6 (embodiment 1 gained compound citric acid powder), divide the morning, twice administration in afternoon, 5d, continue to observe 30d after drug withdrawal continuously, in experimentation, the clinical manifestation of chicken and morbidity, death condition respectively organized in record at any time; The chicken that dies of illness is cutd open inspection, observe its pathological change, get the tissues such as nose, tracheal secretion, lung and air bag and carry out the mycoplasma separation and Culture, carry out simultaneously the serum plate agglutination test to determine the cause of death; To not dead chicken blood sampling, separation of serum detects anti-chicken virus mycoplasma antibody with plate agglutination test.
2 index of assessment of curative effects
(1) infection rate: calculate medication and not medication number of clinical symptoms occurs and account for experimental chicken quantity.
(2) average weight gain according to test just and respectively organize the body weight of chicken, the average weight gain of every group of test chicken of calculating during off-test.
When (3) air bag damaged the slip off-test, each group was randomly drawed 5 of chickens, cutd open inspection and observed the major organs pathological changes such as air bag, lung, liver, the heart, and the degree of injury of air bag is carried out rank scores.
Press H.W.Yoder the air bag pathology damage is divided 5 grades.
0 grade: air bag is normal, and is thin and transparent, remembers 0 minute.
1 grade: air bag only has the grey area or the yellow that slightly thicken to ooze out speckle, remembers 2 minutes.
2 grades: the part air bag is easily seen Lycoperdon polymorphum Vitt to yellow and is oozed out, and foam sometimes occurs, and air bag thickens, and remembers 4 minutes.
3 grades: most of air bag thickens, and is covered with the cheesy exudate of a large amount of yellow-whites, remembers 6 minutes.
4 grades: almost whole air bag is covered with the cheesy exudate of yellow-white, and air bag seriously thickens, and remembers 8 minutes.
Average pathology damage score=all the chicken air bag injury tolerance summation/tested chicken numbers of chicken air bag.
Damage according to air bag the result of scoring and calculate air bag damage minimizing percentage rate.
Air bag damage minimizing percentage rate=(infecting every chicken air bag damage average mark of every chicken air bag damage average mark-test group of matched group)/infect every chicken air bag of matched group to damage average mark.
Table 14 therapeutic test grouping and processing
3 result of the tests
Aspect sickness rate, p-Coumaric Acid is high, middle dosage, low dose group sickness rate are respectively 10%, 10%, 20%, and tylosin group sickness rate is 40%.Aspect survival rate, three groups of p-Coumaric Acids are respectively 100%, 100% and 90%.The body weight change of the high, medium and low dosage group of p-Coumaric Acid administration postoperative infection broiler sees Table 15.The relative weight gain rate is respectively 84.5%, 75.6% and 77.8%, and wherein the high dose group significance is higher than the tylosin matched group, and utmost point significance is higher than infecting matched group.This shows that p-Coumaric Acid can increase the body weight of broiler, and is favourable to growth of meat chicken.
The impact of table 15 p-Coumaric Acid on broiler weight
The impact of table 16 p-Coumaric Acid on the damage of broiler air bag
Annotate: air bag damage minute=(torso bag damage minute+damage of abdominal cavity air bag minute)/cut open inspection chicken quantity; Air bag damage slip=(infecting matched group-test group air bag damage integration)/infect the matched group air bag to damage long-pending.
A-BBe not all significant difference (P＜0.05) with letter sign in string;
A-CBe not all difference extremely significantly (P＜0.01) with letter sign in string.
The demonstration of table 16 result, three dosage group air bags damage slips of p-Coumaric Acid are respectively 78.27%, 88.22% and 91.62%, and the tylosin matched group is 74.35%.The middle and high dosage group of p-Coumaric Acid significance is lower than the tylosin matched group.
The observation of curative effect of experimental example 5 p-Coumaric Acid treatment bird flu H9 subtype viral infections
One, laboratory animal and experiment grouping situation:
1.1 laboratory animal: clinical 30 age in days morbidity broiler, disease time has reached 12 days.The main manifestations snore, drop tears, cough, lassitude, be off one's feed, have the phenomena of mortality to occur, through cut open inspection, this chicken group of serodiagnosis is the respiratory tract disease that is caused by bird flu H9 Subtypes.
1.2 the tested medicine described p-Coumaric Acid oral liquid that is embodiment 4, jumpbogroup contrasts for medicine with astragalus polysaccharides (Hebei Anguo Rui Gao pharmaceutcal corporation, Ltd produces, lot number 20080803).The drinking-water administration is adopted in test, morbidity chicken group, uses continuously 5 days, and grouping and administrated method are as shown in table 17 below.
Table 17 experiment grouping and dosage
Two, test method and observation index
Medicine drinking-water is used in conjunction 5 days.Observe every day animal subject spirit, search for food, drinking-water, feces, breathing situation and death condition, and record.Observed again after medication is complete 10 days, and do following curative effect index evaluation:
Calculate mortality rate, the relative weight gain rate (body weight of every chicken according to on-test and when finishing calculate the average weight gain of weightening finish and every group of chicken, and take the weightening finish of not medication matched group as 100%, each group weightening finish obtains respectively organizing the relative weight gain rate by comparison).
Three, result of the test
Viewing test group chicken group, p-Coumaric Acid chicken group spirit is good than jumpbogroup, but the symptoms such as still existence is shed tears, dyspnea, cuing open seizure test medicine group broiler after off-test finds: compare with the sick chicken of jumpbogroup matched group, the sick chicken tracheorrhagia of p-Coumaric Acid sx↓, but still have more yellow mucus, the lungs edges has slightly and oozes, the slight swelling of kidney; And jumpbogroup cuts open the sick chicken of inspection and finds that tracheorrhagia is serious, has more yellow mucus, and part one forms yellow dried network sample material tamper, lungs except the edge has slightly ooze, hemorrhage serious (accounting for 4/5 area), kidney swelling is obvious.
The impact of table 18 p-Coumaric Acid on survival rate, weightening finish
Annotate:
A-BBe not all significant difference (P＜0.05) with letter sign in string;
The relative weight gain rate=experimental group weightening finish/not medication matched group weightening finish * 100%.
Each group weightening finish of test and survival rate situation are shown in table 18: p-Coumaric Acid shows dose-effect relationship on rate of body weight gain, high dose group the relative weight gain rate reaches 165%, and survival rate is 99.53%; Middle dosage group rate of body weight gain and survival rate are respectively 162.5% and 99.3%; Low dose group rate of body weight gain and survival rate are respectively 142.5% and 98.66%, are significantly higher than astragalus polysaccharides matched group (135.0% and 94.66%).Aspect survival rate, high dose group, middle dosage group significance are higher than not medication matched group (P＜0.05), and be not remarkable with astragalus polysaccharides matched group difference.Aspect the relative weight gain, high, middle dosage group significance higher than astragalus polysaccharides matched group (P＜0.05).
In summary, p-Coumaric Acid can help to reduce mortality rate on the respiratory tract disease that the bird flu H9 hypotype for the treatment of the clinical generation of poultry causes, improves survival rate, increases growth of meat chicken, and the performance good therapeutic effect has good using value.
The observation of curative effect of experimental example 6 p-Coumaric Acid treatment mice avian influenzas
One, laboratory animal and experiment grouping situation:
1.1 laboratory animal: 18-22 gram SPF level BALB/C mice, male and female half and half are raised in the negative pressure isolator of 3 grades of laboratorys of bio-safety, and feedstuff and drinking-water are through autoclaving.
1.2 counteracting toxic substances strain: bird flu HB-bp Strain (A/Chicken/Hebei/102/2005) causes mortality (LD50) through the mice half and is determined as 10
-4.33/ 0.1mL.Counteracting toxic substances 0.1mL/, collunarium.
1.3 tested medicine: be the described p-Coumaric Acid oral liquid of embodiment 4, be divided into three concentration (100mg/kg body weight, 50mg/kg body weight and 25mg/kg body weight), matched group medicine amantadine, 15mg/kg body weight (A Hohnson Matthey Company, the U.S., Lot10118375, analytical pure are 99%) contrast as medicine.After counteracting toxic substances, after 12 hours, test mice adopts the gavage oral administration, is using 5 days continuously, and grouping and administrated method are as shown in table 19 below.
Table 19 experiment grouping and dosage
Two, test method and observation index
After counteracting toxic substances, gavage is used in conjunction 5 days, and observe mice spirit every day, search for food, drinking-water, feces, breathing situation and death condition, and record.Observed again after medication is complete 5 days, and do following curative effect index evaluation:
Calculate mortality rate, the relative weight gain rate (every Mus body weight according to on-test and when finishing is calculated weightening finish and every group of average weight gain).
Lungs index (lungs weight/body weight) and lungs index suppression ratio (infecting matched group-test group lungs index/infection matched group lungs index x 100).
Pulmonary hemorrhage area: Pulmonary hemorrhage area index=bilateral Pulmonary hemorrhage area projection/lungs area x100; The hemorrhage area of Pulmonary hemorrhage suppression ratio=infection matched group-hemorrhage area x 100 of test group Pulmonary hemorrhage area/infection matched group.
Three, result of the test
The impact of 1 the relative weight gain rate and survival rate:
The results are shown in Table 20 and 21.After the test group drug oral, the relative weight gain rate is respectively 95.04%, 91.18% and 77.03%, and infecting matched group is 45.84%, through the statistical analysis significant difference.Survival rate is respectively 87.5%, 87.5% and 75%, and amantadine group and infection matched group are respectively 37.5% and 37.5%, and through statistical analysis, testing drug is high, middle dosage group is compared difference extremely significantly (P＜0.01) with the amantadine matched group.
After table 20 oral drugs on the impact of Mouse Weight
Annotate:
A-B, B-CBe not all significant difference (P＜0.05) with letter sign in string;
A-CBe not all significant difference (P＜0.01) (lower same) with letter sign in string;
The relative weight gain rate=experimental group weightening finish/normal healthy controls group weightening finish * 100%.
Table 21 mouse death rate, survival rate
2 impacts on mice relevant diseases index:
The results are shown in Table 22 and 23.High, medium and low three the dosage group lungs index suppression ratio of testing drug are respectively 49.0%, 31.52% and 10.41%, the amantadine matched group is 41.39%, statistical analysis shows that high dose group, middle dosage group and amantadine matched group difference are not remarkable, but low dose group significant difference (P＜0.05).From the Pulmonary hemorrhage area index, the hemorrhage suppression ratio of testing drug is respectively 67.38%, 53.84% and 35.38%, and the amantadine matched group is 62.31%, and the statistical testing results is identical with lungs index suppression ratio.
The lungs index variation of table 22 mice
The Pulmonary hemorrhage situation of table 23 mice
Above result shows p-Coumaric Acid in the test for the treatment of bird flu infecting mouse, and by the 100mg/kg body weight, the 50mg/kg body weight is oral can significantly reduce the mortality rate that the artificial challenge causes, effect is better than amantadine amine matched group; Reducing on pathological changes, its effect and amantadine matched group difference are not remarkable, and the prompting testing drug has good using value in the infection that the treatment bird flu causes.
Claims (3)
1. the application of p-Coumaric Acid in the medicine of the disease of preparation control infected chicken virus mycoplasma HS strain.
2. application according to claim 1, is characterized in that, this medicine contains the p-Coumaric Acid of effective dose.
3. application according to claim 2, is characterized in that, this medicine is powder, tablet, granule or oral liquid.
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