CN101530475A - Application of pink plumepoppy herb extract in veterinary drugs of economic animals - Google Patents
Application of pink plumepoppy herb extract in veterinary drugs of economic animals Download PDFInfo
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- CN101530475A CN101530475A CN200910043145A CN200910043145A CN101530475A CN 101530475 A CN101530475 A CN 101530475A CN 200910043145 A CN200910043145 A CN 200910043145A CN 200910043145 A CN200910043145 A CN 200910043145A CN 101530475 A CN101530475 A CN 101530475A
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Abstract
The invention relates to an application of pink plumepoppy herb extract in veterinary drugs of economic animals; the pink plumepoppy herb extract is used for preparing medical feed additives of the veterinary drugs which are used for enhancing the growth of the economic animals and increasing conversion rate of the feed or veterinary drugs which has better inhibiting action and disinfecting action to common pathogenic bacteria in livestock and poultry, such as listeria monocytogenes, haemophilus and pasteurella.
Description
Technical field:
The present invention relates to the extract that obtains from the plant Herba Macleayae Cordatae (Macleaya cordata (Willd) R.Br.) that contains benzylisoquinoline alkaloid (Benzylisoquinoline Alkaloid) and promoting economic animal growth and feedstuff medicated premix of improving food conversion ratio and the application aspect the veterinary drug.Mainly contain the benzylisoquinoline total alkaloids in the extract, wherein comprise Sanguinarine, chelerythrine, protopine, allocryptopine, 13-methyl-13,14-dihydro-[1,3, dihydro allocryptopine etc.
Background technology:
For a long time, owing to use growth promotion health-care agents such as antibiotic, chemical synthetic drug, hormone widely in animal feed and the veterinary drug, this class additive has also brought human a lot of harm when promoting animal husbandry development.The drawback of antibiotic abuse is more and more outstanding.Mainly show: the immunity degradation of autogenous infection and superinfection, microorganisms Drug resistance, body, residual toxic and side effects and environmental pollution.Under these circumstances, countries in the world have all been formulated law, the rule and standard relevant with the feedstuff medicated premix one after another, the use of standard and supervision medicated feed additive, thereby the interests of maintenance country and consumer.Each member state of European Union carries out the strictest feedstuff drug use system.European Union announced up-to-date " feed additive criterion " in 2003, under the pressure of the pressure of consumer and medical science aspect, and this criterion regulation, the medicine except coccidiosis inhibitor and infusorian inhibitor was all stopped using on January 1st, 2006.Now, the mankind urgently wish back to nature, recover one's original simplicity, and comply with this world trends, around " healthy animal, safety food, healthy human " this theme, and the countries in the world antibiotic secure replacement product that begin one's study one after another.Natural plant medicines structure uniqueness, be difficult for producing drug resistance, in environment, can degrade voluntarily, be unlikely to medium-term and long-term residual or by the food chain enrichment at agricultural product, livestock products, do not cause irreversible breaking to environment, to the relative low toxicity of people and animals, meet the requirement of green ecological animal husbandry to medicine, be the important development direction of following veterinary drug.There are extremely abundant plant and natural product resource in China, from the natural product resource, seek new antibiotic substitute matter, determine its active skeleton, excavate lead compound, screen its more effective chemical compound, have extremely vast potential for future development and crucial meaning.
Herba Macleayae Cordatae (Macleaya cordata (Willd.) R.Br.), having another name called horn grass, horn bar, Paulownia bar, suddenly reining in back is the perennial tall and big draft of Papaveraceae Macleaya, the herbal document of putting down in writing Herba Macleayae Cordatae the earliest is a supplement to the Herbal.Now unified called after Herba Macleayae Cordatae.Herba Macleayae Cordatae extract, mainly be distributed in Papaveraceae, Rutaceae, in the natural plants such as Berberidaceae, mainly contain Sanguinarine (Sanguinarine) in the total alkaloids that falls back, chelerythrine (Chelerythrine), bocconine (Bocconine), the peaceful alkali of Herba Macleayae Cordatae (Bocconoline), methoxyl group chelerythrine (Chelilutine), 13-methyl-13,14-dihydro-[1,3 (Dihydrosanguinarine), dihydrochelerythrine benzo phenanthridines type alkaloid and protopines (Protopine) such as (Dihydrochelerythrine), α-allocryptopine (α-Allocryptopine), β-allocryptopine (former tropine type alkaloid and Norsanguinarine such as β-Allocryptopine), Oxysanguinarine, Homochelidonine, Coptisine, Berberine, Chelidonine, protozoa alkali such as Chelirubine.Modern pharmacological research shows that Herba Macleayae Cordatae has significantly antibiotic, parasite killing, improves liver function, improves effects such as immunity and antitumor.
In the application facet of Herba Macleayae Cordatae, the Macleaya cordata injection of including in Ministry of Agriculture's veterinary drug quality standard be by Herba Macleayae Cordatae fruit through extracting, separate the sterile water solution of the alkaloid sulfate of making, the function that it has anti-inflammation cures mainly Hakuri, the yellow scours of piglet; Yu Jiansheng (2007) with in infruit of Herba Macleayae Cordatae and the root through the active ingredient total alkaloids that extracts make injection, oral liquid is obtained better effects in order to treatment piglet pujos blancos, fowl cholera disease; Yu Jiansheng etc. cooperate Herba Macleayae Cordatae and make compound Macleaya cordata injection patent applied for (patent No. ZL 200510020409.0) with Herba Andrographis, it has wide spectrum clearing heat, releasing toxin, removing swelling, anti-bacteria and anti-virus anti-inflammatory effect, is mainly used in the treatment poultry and suffers from influenza, diarrhoea dysentery, piglet pujos blancos and yellow scours etc.The application that comprehensive literature can draw Herba Macleayae Cordatae extract now mainly is the veterinary drug with treatment livestock and poultry animal digestive tract disease, and administering mode is many based on injection.The Herba Macleayae Cordatae extract of mentioning of the present invention, be that total alkaloids more than 60% is added on as the veterinary drug raw material and carries out daily feeding in the feedstuff, in order to the growth that promotes economic animal with improve food conversion ratio, relevant report is not seen in this application as veterinary drug and medicated feed additive as yet.
In this year, along with livestock and poultry breeding industry develops rapidly and the raising of intensification level, cultivation density is increasing, has caused the incidence rate of some diseases more and more higher.Pathogenic microorganism is very serious to the hazardness of livestock and poultry breeding industry, often causes the disease of digestive tract, respiratory tract, makes young stock poult growth retardation, and adult poultry are fattened difficulty.Cause serious economy loss to livestock and poultry breeding industry.Select high-efficiency low-toxicity, medicament easy to use to prevent and treat the problem that has become people generally to be concerned about.
Summary of the invention:
The inventor extracts macleaya cordata total alkaloid and it is carried out bioactivity research finds to have antibacterial widely from the Herba Macleayae Cordatae plant, promote economic animal growth and improving food conversion ratio effect, specifically tests and sees below.
The Herba Macleayae Cordatae extract that the present invention mentioned is used for preparing medicated feed additive that promotes economic animal growth veterinary drug or the veterinary drug that poultry encountered pathogenic bacteria pasteurellosis bacillus, Listeria monocytogenes and haemophilus is had good inhibitory effect and killing action.
The present invention is by Herba Macleayae Cordatae extract being used to be prepared into veterinary drug or medicated feed additive.Mainly containing effective constituent in the Herba Macleayae Cordatae extract is that active skull cap components benzylisoquinoline alkaloid class can be used for suppressing and killing intravital pathogenic microorganism, and the promotion economic animal grows and improves food conversion ratio; Or as the raw material for preparing veterinary drug.
Described Herba Macleayae Cordatae extract derives from bloodroot Herba Macleayae Cordatae plant, and its sophisticated fruit pod or leaf or both mixtures are prepared from through extraction.Because of Herba Macleayae Cordatae extract of the present invention comprises Sanguinarine, chelerythrine, protopine, allocryptopine, 13-methyl-13,14-dihydro-[1,3, dihydro allocryptopine etc.
The Herba Macleayae Cordatae extract that the present invention mentioned is extraction separation, the refining high-purity Herba Macleayae Cordatae extract component that obtains from the Herba Macleayae Cordatae plant; Adopt acid extraction, the aqueous alkali post precipitation, with the post precipitation alcohol extraction, concentrate the back with concentrated acid sink salt prepare total alkaloids more than 60%.Its Herba Macleayae Cordatae extract content is to detect by the HPLC method, calculates the content of the former alkali of total alkaloids in the Herba Macleayae Cordatae extract with the total content of Sanguinarine and chelerythrine.
Herba Macleayae Cordatae extract mainly contains benzylisoquinoline alkaloid, and can exist with the biological former alkali of benzylisoquinoline, its form of hydrochlorate, disulfate or dihydric phosphate.
The present invention is inhibition and the pathogenic microbe killing that Herba Macleayae Cordatae extract is made as effective ingredient, promotes economic animal growth and the effect of improving food conversion ratio that good result is arranged.The application of Herba Macleayae Cordatae extract is to comprise independent use, perhaps uses jointly with other antibacterials.When being used, also has the effect of good resistance parasite with other antibiotic veterinary drugs.The administration concentration of Herba Macleayae Cordatae extract in veterinary drug or medicated feed additive is preferably 0.1-30ppm.Count comparatively preferably 0.1-5ppm as the concentration that medicated feed additive adds in pig, the chicken feedstuff with total alkaloids.
Add concentration in pig, the chicken feedstuff in most preferably 1-5ppm of total alkaloids as medicated feed additive.
Veterinary drug of the present invention can pass through form administrations such as mixed feeding, drinking-water.Herba Macleayae Cordatae extract is added various dosage form-pre-mixing agents that the diluent corresponding auxiliary material can be made into or water preparation etc., be applied to suppress and pathogenic microbe killing, promote aspects such as economic animal pig, chicken grow, improve food conversion ratio to have good market prospect.
The specific embodiment
Following examples are intended to illustrate the present invention rather than limitation of the invention further.
The preparation method of embodiment 1 Herba Macleayae Cordatae extract
Get infruit of Herba Macleayae Cordatae, 0.5% aqueous sulfuric acid with 20 times of amounts extracts, and arrives 8-10 with adjusting PH with base then, behind the precipitation separation, reuse 90% ethanol extraction, behind the partial concentration extracting liquid filtering, add concentrated sulphuric acid and separate out a large amount of salmon pink precipitate, obtain Herba Macleayae Cordatae extract after the drying, measure total biological content through HPLC and be about 66.4% (with the content total of former Sanguinarine and chelerythrine, as follows), wherein Sanguinarine is about 46.4%, and chelerythrine is about 20%.
The preparation of embodiment 2 Herba Macleayae Cordatae extract pre-mixing agents
The Herba Macleayae Cordatae extract that embodiment 1 method makes takes by weighing 100g,, use cracker for medicine to pulverize, cross 120 mesh sieves, standby; Take by weighing medical starch 3900g again.Use small-sized mixer fully to mix 15 minutes Herba Macleayae Cordatae extract and medical starch, check the coefficient of variation＜0.5, obtain Herba Macleayae Cordatae extract pre-mixing agent 4000 grams.
Embodiment 3 Herba Macleayae Cordatae extract are to poultry encountered pathogenic bacteria body outer suppressioning test
Select Herba Macleayae Cordatae extract for use, and to measure its content be research experiment, and the solution that embodiment 1 is made the Herba Macleayae Cordatae extract preparation carries out extracorporeal bacteria inhibitor test to common animal pathogens of poultry such as haemophilus, Listeria monocytogenes, pasteurellosis bacillus, streptococcus respectively.By sterile working's rules, under aseptic condition, topple over the culture medium flat plate of corresponding strain correspondence, the corresponding bacterial classification inoculation thing of coating above, treat that flat board solidifies after, paste and add the drug susceptability test paper sheet, with aseptic nipper scraps of paper peace is hardened and closes closely.Do contrast with the filter paper that is soaked with chlortetracycline simultaneously.Every duplicate samples is done 3 parts, results averaged.Be inverted for 37 ℃ and cultivate, and observe fungistatic effect, measure the diameter of inhibition zone, judge sensitivity in 24h.
Criterion: inhibition zone diameter has been judged as bacteriostasis greater than 7mm person, and inhibition zone diameter is less than or equal to 7mm does not have bacteriostasis, and the big more explanation fungistatic effect of bacteriostatic diameter is good more.
The result detects and shows: the concentration of Herba Macleayae Cordatae extract and chlortetracycline is under the 100ug/ml condition, haemophilus, Listeria monocytogenes, and the bacteriostatic diameter of pasteurellosis bacillus and 4 kinds of poultry encountered pathogenic bacterias of streptococcus all greater than 7mm, demonstrate good bacteriostasis table (1).
Table 1 Herba Macleayae Cordatae extract is to the influence (unit: mm) of bacteriostatic diameter
Adopt tube dilution method, compare, measure the minimum inhibitory concentration (MIC) of the medicinal liquid that bacteriostatic activity is arranged with chlortetracycline.Herba Macleayae Cordatae extract is a test group, get 13 of sterile test tube for every group, be arranged in a row, remove the 1st pipe and add the bacterium liquid of 1.8mlMH with 1000 times of meat soup dilutions, all the other every pipes add MH meat soup 1ml, add the solution stock solution 0.2ml mixing of preparing by example 1 gained Herba Macleayae Cordatae extract at the 1st pipe, draw 1ml to the 2 pipes then, draw 1ml to the 3 pipes behind the mixing again, so continuously doubling dilution to the 12 pipes, and absorption 1ml discards from the 12nd pipe, and the 13rd pipe is not for containing the growth control of medicine.Cultivating 24h for 37 ℃, is minimal inhibitory concentration (MIC) with the least concentration of no bacterial growth.
The testing result of minimal inhibitory concentration shows: Herba Macleayae Cordatae extract all has a good fungistatic effect to haemophilus, Listeria monocytogenes, pasteurellosis bacillus, 4 kinds of poultry encountered pathogenic bacterias of streptococcus bacterial strain, and Gram-positive and gram negative bacteria are all had good fungistatic effect.As seen Herba Macleayae Cordatae extract has the broad-spectrum bacteriostasis.Though result of the test shows the minimum fungistatic effect concentration of Herba Macleayae Cordatae extract and is higher than chlortetracycline group (table 2), antibiotic as an alternative medicine, its source is natural, fast, residual low, advantage, the good market prospect such as side effect is little of degraded.
Table 2 Herba Macleayae Cordatae extract is to minimal inhibitory concentration MIC (unit: ug/ml)
Embodiment 4 Herba Macleayae Cordatae extract are to the influence test of ablactational baby pig growth performance
EXPERIMENTAL DESIGN: single factor design is adopted in this test.Choose 28 ± 2 age in days body weight close (8.3 ± 0.26kg) wean are long white * 120 of healthy piglets of big York two-way cross.Fed 3 days with basal diet earlier before on-test, be divided into 12 hurdles by first starting weight, male and female half and half principle then, be divided into 3 processing, each handles 4 hurdles, 10 pigs in every hurdle.Handle one: the blank group; Handle two: the chlortetracycline that adds 100mg/kg; Handle three: the Herba Macleayae Cordatae extract pre-mixing agent product that adds embodiment 2 preparations of 45mg/kg.This test is carried out on new five Yongan branch company of rich limited company pig farms in the Hunan.
Feeding and management: all test piglets are raised in closed animal house, and the child care hurdle is high bed metal slatted floor ferrum cage, and the nipple-shape water fountain is freely drunk water.Other management more solitos such as sterilization, immunity are carried out.Manually add material, feed in 7:00,11:00,15:00 and 19:00 every day, guaranteeing there is not free choice feeding under the dyspeptic prerequisite, severe diarrhoea or disease treatment in time or superseded occurs.
Record index: average daily gain (ADG), average daily ingestion amount (ADFI), feed conversion rate (FCR).
The total head of diarrhea rate=diarrhoea piglet head/piglet * 100%
Table 3 Herba Macleayae Cordatae extract is to the influence of piglet growth performance
Annotate: the complete person inequality of colleague's letter represents significant difference (P＜0.05) in the mark.Down together.
As shown in table 3, the average daily ingestion amount of 3 processed group and average daily gain are followed successively by from high to low to be won
Return extract group, positive controls (chlortetracycline), the blank group.Compare with the blank group, add Herba Macleayae Cordatae extract in the daily ration and improved average feed intake 12.3%; Average daily gain 16.9%; Feedstuff-meat ratio 4.32% (p＜0.05) that descended.The result shows that adding Herba Macleayae Cordatae extract in the daily ration has improved feed intake and the daily gain of piglet significantly, and the reduction of feedstuff-meat ratio has effectively improved the growth in piglets performance.The effect of comparing with the matched group of antibiotic chlortetracycline is suitable.
Table 4 Herba Macleayae Cordatae extract is to the influence of piglet diarrhea situation
As shown in table 4, positive controls, Herba Macleayae Cordatae extract are compared the remarkable diarrhea rate (P＜0.05) that reduced with matched group.This test is presented in the piglet diet to be added Herba Macleayae Cordatae extract and has the growth of promotion and the effect of prevention diarrheal, has suitable effect with chlortetracycline.
Embodiment 5 Herba Macleayae Cordatae extract are tested the meat INFLUENCE OF YUCCA EXTRACT
EXPERIMENTAL DESIGN: single factor design is adopted in this test.Choose long white * 60 of healthy piglets of big York two-way cross.Fed 3 days with basal diet earlier before on-test, be divided into 6 hurdles by first starting weight, male and female half and half principle then, be divided into 2 processing, each handles 3 hurdles, 10 pigs in every hurdle.Handle one: the blank group; Handle two: the Herba Macleayae Cordatae extract pre-mixing agent product that adds embodiment 1 preparation of 5ppm.
Table 5 Herba Macleayae Cordatae extract is to the influence of barren sow diarrhoea situation
As in the table 5 as can be known, experiment shows that for comparing with the blank group, the average feed intake of Herba Macleayae Cordatae extract group has improved 2.2%, daily gain has improved 9.3%, and ((p＜0.05) significant difference, feedstuff-meat ratio have reduced by 6.6% (p＜0.05) significant difference.As seen the Herba Macleayae Cordatae extract that re-adds 5ppm at daily ration improves growth performance indexs such as barren sow daily gain and efficiencies of feed utilization good effect.
Embodiment 6 Herba Macleayae Cordatae extract are tested the growth of meat chicken Effect on Performance
EXPERIMENTAL DESIGN: the single factor experiment design is adopted in this test, selects 450 the 1 yellow chickens of age in days for use.For examination chicken well-grown, healthy anosis.The body weight basically identical.To try chicken and be divided into 3 groups at random, every group of 6 repetitions, each repeats 25 chickens.Experimental period is 49 days.Experiment is divided into 3 groups: group 1 is matched group (not adding antibiotic and Herba Macleayae Cordatae extract); Group 2 is added 30mg/kg chlortetracycline; Group 3 is added the Herba Macleayae Cordatae pre-mixing agent of 100mg/kg embodiment 2 preparations.
Feeding and management: the test hen house is open, and gravity-flow ventilation, illumination are 14L:10D.Write down temperature, humidity in the hen house every day.The examination chicken is adopted high bed to put down and supports, and measures quantity-unlimiting feeding; Freely drink water, scale of feeding is by recommending nutritional requirement to decide in conjunction with actual feed intake.Carry out hygienic cleaning and sterilization according to a conventional method.Experimental period, keep crib, tank sanitation and hygiene.
Record index: average daily gain (ADG), average daily ingestion amount (ADFI), feed conversion rate (FCR).
Table 6 Herba Macleayae Cordatae extract is to growth of meat chicken Effect on Performance result
Result as shown in table 6 shows: the average daily ingestion amount of 3 processed group and average daily gain are followed successively by Herba Macleayae Cordatae extract group, positive controls (chlortetracycline), blank group from high to low.Compare with the blank group, add Herba Macleayae Cordatae extract in the daily ration and improved average feed intake 0.3%; Average daily gain 8.12%; Feedstuff-meat ratio has descended 9.52%.Add Herba Macleayae Cordatae extract and effectively reduce the broiler death toll simultaneously in daily ration, can improve the growth performance of yellow chicken significantly, adding Herba Macleayae Cordatae extract in daily ration has the effect suitable with chlortetracycline.
Embodiment 7 Herba Macleayae Cordatae extract are to the control test of haemophilus parasuis disease
Hyperpyrexia disease takes place in certain experiment 12 2 monthly ages of pig farm piglet, and sick pig performance has fervescence (more than 40 ℃), and spirit is depressed, and appetite descends, dyspnea, and disorderly thick by hair, skin rubefaction even blue is become thin, dyspnea, arthroncus is walked lamely etc.All can see gram-negative tiny bacillus after dyed, ne ar is various, and the person is in the majority with bacillus exilis, and long and crooked thread thalline is arranged.Be the dense club shape that dyes in the two poles of the earth individually, be accredited as haemophilus parasuis.Ill pig daily to drink the concentration that Herba Macleayae Cordatae extract is mixed be the water preparation of 30ppm, logotype 6 days.In treatment, pig house and surrounding are carried out thorough disinfection spray, once a day, logotype 7d.Swinery gradually recovers one's health after 2 weeks.
Claims (7)
1, the application of Herba Macleayae Cordatae extract in the economic animal veterinary drug is characterized in that: Herba Macleayae Cordatae extract is used for preparing the medicated feed additive of the veterinary drug that promotes the economic animal growth and improve food conversion ratio or poultry encountered pathogenic bacteria Listeria monocytogenes, haemophilus and pasteurellosis bacillus is had the veterinary drug of good inhibitory effect and killing action.
2, the application of Herba Macleayae Cordatae extract according to claim 1 in the economic animal veterinary drug is characterized in that: described Herba Macleayae Cordatae extract origin comes from the bloodroot Herba Macleayae Cordatae, extracts to be prepared from from its sophisticated fruit pod or leaf or both mixture.
3, the application of Herba Macleayae Cordatae extract according to claim 1 and 2 in the economic animal veterinary drug, it is characterized in that: mainly contain benzylisoquinoline alkaloid in the Herba Macleayae Cordatae extract, any form with the former alkali of benzylisoquinoline alkaloid or its hydrochlorate, disulfate or dihydric phosphate in extract exists.
4, Herba Macleayae Cordatae extract according to claim 1 is in the application of economic animal veterinary drug, it is characterized in that: count 0.1-5ppm as the concentration that medicated feed additive adds in pig, the chicken feedstuff with total alkaloids, count 0.1-30ppm with total alkaloids as the concentration that veterinary drug adds in pig, the chicken feedstuff.
5, Herba Macleayae Cordatae extract according to claim 1 is characterized in that in the application of economic animal veterinary drug: count 1-5ppm as the concentration that medicated feed additive adds in pig, the chicken feedstuff with total alkaloids.
According to of the application of the described Herba Macleayae Cordatae extract of claim 1, it is characterized in that 6, described medicated feed additive or veterinary drug are mixed with feedstuff and fed oral mode administration at economic animal feedstuff herbal medicine.
7, Herba Macleayae Cordatae extract according to claim 1 is characterized in that in the application of economic animal veterinary drug: described medicated feed additive or veterinary drug are the occupation modes with pre-mixing agent or water preparation.
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