CN105146151A - Antibacterial peptide immunomodulatory feed additive for pigs - Google Patents

Antibacterial peptide immunomodulatory feed additive for pigs Download PDF

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CN105146151A
CN105146151A CN201510523587.9A CN201510523587A CN105146151A CN 105146151 A CN105146151 A CN 105146151A CN 201510523587 A CN201510523587 A CN 201510523587A CN 105146151 A CN105146151 A CN 105146151A
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pidotimod
pig
feed additive
pigs
immunomodulatory
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CN105146151B (en
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李卫芬
付爱坤
傅罗琴
陈洪亮
姜礼辉
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Zhejiang University ZJU
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Zhejiang University ZJU
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Abstract

The present invention discloses an antibacterial peptide immunomodulatory feed additive for pigs. The feed additive consists of the following components in parts by weight 1-5 parts of bacillus amyloliquefaciens SC06 at a concentration of 10^9 cfug, 1 part of pidotimod, 3 parts of zeolite powder, and 1-5 parts of corn starch. The antibacterial peptide immunomodulatory feed additive for pigs can overcome many problems including pig body immunosuppression, low disease resistance, slow growth, etc. in the current breeding process, and the antibacterial peptide immunomodulatory feed additive for pigs has characteristics of being easy in preparation, easy to use, significant in effects, etc., and thus is very good in promotion and use values.

Description

Pig bacterium peptide immunological regulation feed addictive
Technical field
The invention provides preparation and the application thereof of boar bacterium peptide immunological regulation feed addictive.
Background technology
Ubiquity immunosupress phenomenon in pig breeding process at present, this is caused by many factors, comprises pathogenic bacterial infection (as blue-ear disease, smoothing filter operator, pseudoabies, swine fever, parvovirus, swine flu, the virus such as parvovirus and disease of breathing, Haemophilus parasuis, contagious pleuropneumonia, salmonellosis, the parasitic infection of bacterium and the toxoplasmosis etc. such as eperythrozoonosis) and non-pathogenic factors, in non-infectious factor, there is toxin poisoning (mycotoxin: as aflatoxin, the red enzyme ketenes of corn, T-2 toxin, FT, ochratoxin etc.), the unreasonable use of antibiotic and medicine is (as chloramphenicol, furazolidone, streptomysin, neomycin, gentamicin, kanamycins, chaff cortin, tetracycline, terramycin, metacortandracin, cortisone, androgen, testosterone, sulfa drugs etc.), nutritional deficiency, epidemic disease epidemic disease consumption is (over much dosage vaccinate, inoculation times is too much, and vaccine inoculation kind is too much) excessively, various stress factor is (excessively cold, overheated, turn group and mix group, crowded, childbirth, wean, castration, reload, long-distance transport, noise, hurriedly drive) and inherent cause (congenital immune deficiency, chromosome abnormality, congenital thymic aplasia disease, congenital Development of The Spleen is not congruent) etc.The congenital property of above immunosuppressive agent meeting coup injury pig and adaptive immune system; The biologically active of Immunosuppression cell, reduce the ability of immunocyte present antigen, weaken the immune response function of immunocyte, cause body to occur immunological paralysis and immune tolerance, and can Lymphocyte Apoptosis etc. be caused; Cause vaccine immunization failure, lack specific immunity; Cause body's immunity low, specificity and non-specific antibody are all in extremely low level, and premunition declines, and brings out multiple cause of disease mixed infection and scabies secondary infection, finally form cad pig or the death of the not clear cause of disease.Therefore, the immunosupress how controlling pig has become Large-scale pig farm urgent need to solve the problem.Therefore market is starved of determined curative effect, pig easy to use Immune-enhancing effect product.
The dipeptides that Pidotimod (pidotimod) is made up of pyroglutamic acid and Thiazolidinecarboxylacid acid two amino acid.Researched and developed by Italian Poli chemical company, listing in 1993, is a kind of immunomodulator, can promotes nonspecific immune reaction, can promote specific immune response again.By finding the research of mouse, Pidotimod immunity moderation is mainly through following 6 approach: 1. appropriate Pidotimod can make lymphocytic competence for added value and active raising; 2. the expression of spleen histiocytokine TNF-α and IL6 is promoted, strengthening organism immune response; 3. during immunologic hypofunction, Long-Time Service Pidotimod can make the helper T lymphocyte (CD of reduction 4 +) and suppressor T lymphocyte (CD 8 +) ratio raise and recover normal; 4. NK cell is activated; 5. promote macrophage activity, the phagocytic activity of macrophage increases; 6. the chemotaxis of neutrophil leucocyte is improved rapidly.
In clinical practice, although Pidotimod does not have direct sterilization and antivirus action, but zoopery and clinical research all show, it has obvious antibacterium and viral infection resisting function, this is because Pidotimod by promoting nonspecific immune reaction and the specific immune response of body, can make the significant antibacterium of physical exertion and virus infections effect.In the respiratory tract infection of children's recurrent exerbation, in the treatment of urinary system infection contamination, Pidotimod and antibiotic with the use of, can significantly reduce antibiotic consumption, improve immunity of organisms, delay state of an illness outbreak and mitigation symptoms.In Eaton agent pneumonia, in the treatment of allergic rhinitis, asthma, virus infections and tumor patient or hypoimmunity crowd, the immunologic function of patient can be significantly improved.
The safety research of Pidotimod is found, Pidotimod has good security and tolerance, give all not occur toxic reaction every day 40 times ~ 50 times of maximal therapeutic dose in animal, Pidotimod does not show any impact causing genetic mutation, also reproductive system is not affected, without teratogenesis and forward and backward toxicity of giving a birth.From listing in 1993 so far, there is not yet the report of serious adverse reaction.
Pidotimod is applied to prevention mankind's various bacteria and virus infections as a kind of immunopotentiating agent, but its application in animal productiong have not been reported.
Summary of the invention
The technical problem to be solved in the present invention is to provide preparation and the application thereof of boar bacterium peptide immunological regulation feed addictive.
In order to solve the problems of the technologies described above, the invention provides boar bacterium peptide immunological regulation feed addictive, being made up of the component of following weight portion: bacillus amyloliquefaciens SC06 (10 9cfu/g) 1-5 part, Pidotimod 1 part, zeolite powder 3 parts, cornstarch 5-1 part.
Remarks illustrate:
Bacillus amyloliquefaciens SC06 has and clearly informs in the patent of invention of having authorized " bacillus amyloliquefaciens and uses thereof " (ZL2012103829633).It is preserved in China typical culture collection center, preserving number: CCTCCNo:M2012280.
The pig of the present invention preparation method of bacterium peptide immunological regulation feed addictive is: be simply uniformly mixed by mentioned component.
Pig of the present invention bacterium peptide immunological regulation feed addictive, can overcome the pig body immunosupress in current pig breeding process, premunition low, grow the problems such as slow, this bacterium peptide immunological regulation feed addictive has the features such as easy to prepare, easy to use, Be very effective, thus, have good value for applications.
The pig of the present invention storage conditions of bacterium peptide immunological regulation feed addictive is: room temperature, and the term of validity is 2 years.
During pig of the present invention use actual in bacterium peptide immunological regulation feed addictive, the ratio according to account for pig feed gross weight 0.05% ~ 0.1% adds in pig feed, can feeding in a conventional manner after Homogeneous phase mixing.
Early-stage Study according to inventor finds: Pidotimod is except promoting T cell propagation, antibody generation, improve anti-infective outside, the animal Primary bone marrow macrophage M2 type differentiation that IL-4 also can be promoted to induce and the cell migration of M2 type macrophage and injury repair function, show significant anti-inflammatory properties, and bacillus amyloliquefaciens SC06 (preserving number: CCTCCNo:M2012280) can directly break up by inducing bone marrow macrophage M1 type, show stronger proinflammatory function and Phagocytosis ability; In order in conjunction with the advantage respective in immunological regulation of both Pidotimod and bacillus amyloliquefaciens SC06, spy has invented pig of the present invention bacterium peptide immunological regulation feed addictive.
Detailed description of the invention
Method used in following embodiment is conventional method if no special instructions.
Embodiment 1, the pig preparation of bacterium peptide immunological regulation feed addictive
Take bacillus amyloliquefaciens SC06 (10 9cfu/g) 20 kilograms, bacterium powder, 10 kilograms, Pidotimod pulvis (purity more than 99%), zeolite powder 30 kilograms, cornstarch 40 kilograms; Be packed as 1 kilogram of packaging after abundant mixing, can use.
Application test
1 test material
The outer ternary newborn piglet of DLY, by Zhejiang, joyful feed limited company provides.
Bacillus amyloliquefaciens additive: take bacillus amyloliquefaciens SC06 (10 9cfu/g) 30 kilograms, bacterium powder, zeolite powder 30 kilograms, cornstarch 40 kilograms; Use after abundant mixing.
Pidotimod additive: take 30 kilograms, Pidotimod pulvis (purity more than 99%), zeolite powder 30 kilograms, cornstarch 40 kilograms; Use after abundant mixing.
2 feeding experiments and daily management method
This test adopts single-factor Randomized Designs, and the early-weaned piglets of health is divided into 4 groups, often organizes 4 repetitions.Each repetition 10 weanling pigs, each group basal diet is identical.Test from 21 age in days wean, 28 days by a definite date.Concrete grouping situation is as follows:
Control group (Control): basal diet of feeding;
Test 1 (T1): the basal diet of interpolation 0.1% (% by weight) bacillus amyloliquefaciens additive of feeding;
Test 2 (T2): the basal diet of interpolation 0.1% (% by weight) Pidotimod additive of feeding;
Test 3 (T3): the basal diet of interpolation 0.1% (% by weight) pig bacterium peptide immunological regulation feed addictive (embodiment 1) of feeding.
3 sample collections
Feeding experiment terminates that rear four test group are each at random respectively gets 2 (totally 8) piglets and prepare to wait to kill, and will wait to kill piglet and cut open and kill front 12h and stop eating, early morning is vena cava anterior collection serum on an empty stomach.
Piglet opens abdominal cavity after putting to death, and gathers small intestine and Mucosal samples.Jejunum is used for HE dyeing and transmission electron microscope observing.
4 result of the tests
4.1 affect performance to piglet growth
Feeding experiment result shows, add 0.1% bacillus amyloliquefaciens, 0.1% Pidotimod additive and 0.1% pig bacterium peptide immunological regulation feed addictive in feed can be significantly increased the average daily gain of piglet, wherein 0.1% pig is the highest by the daily gain of bacterium peptide immunological regulation feed addictive, and three kinds of additives do not make significant difference to feed-weight ratio; Specifically as shown in table 1.
Table 1 is on the impact of piglet growth
With a line, different alphabetical person is significant difference (P<0.05)
4.2 impacts that intestine of young pigs gene involved in immunity is expressed
As shown in table 2, compared with the control, add 0.1% bacillus amyloliquefaciens in daily ration and significantly can promote proinflammatory factor IL-6 in piglet ileum, the gene expression of IL-8 and anti-inflammatory factors IL-10, add the expression that 0.1% Pidotimod additive significantly can reduce proinflammatory factor IL-6 and IL-1 α, improve the gene expression of anti-inflammatory factors TGF-β and IL-10 simultaneously, add the gene expression that 0.1% pig bacterium peptide immunological regulation feed addictive promotes proinflammatory factor IL-6 and anti-inflammatory factors TGF-β and IL-10, proinflammatory degree reduces anti-inflammatory properties raising compared with probio, compared with Pidotimod, proinflammatory degree increases, such pig bacterium peptide immunological regulation feed addictive combines the advantage of both bacillus amyloliquefaciens and Pidotimod, there is better two-way immunoloregulation function, can not excessive inflammation be there is when anti-microbial pathogen infects and injure self, ensure that enteron aisle is more healthy.
Table 2 is on the impact of piglet ileal mucous membrane gene expression
4.3 impacts on piglet serum cytokines
As shown in table 3, compared with the control, in daily ration, add the content that 0.1% bacillus amyloliquefaciens significantly reduces proinflammatory factor TNF-α, IFN-γ, IL-6 and anti-inflammatory factors IL-10 in serum simultaneously; Add the content that 0.1% Pidotimod additive reduce further proinflammatory factor TNF-α in serum, IFN-γ IL-6, but significantly improve IL-4 and IL-10 content; Add the content that 0.1% pig bacterium peptide immunological regulation feed addictive reduces proinflammatory factor TNF-α, IFN-γ in serum, IL-6 and IL-10 content equally, but its content is between probio and Pidotimod group, show that piglet is in anti-inflammatory and the pro-inflammatory states of appropriateness, the good immunologic balance state of tool, body is in more healthy state.
Table 3 is on the impact of piglet Cytokine of Serum content
Conclusion
Pig of the present invention bacterium peptide immunological regulation feed addictive significantly can promote piglet growth, this to its improvement enteron aisle and body health, there is appropriate anti-inflammatory and proinflammatory reaction simultaneously, immunologic balance state is relevant preferably.Therefore, pig bacterium peptide immunological regulation feed addictive can directly apply to pig industry.
These results suggest that, pig of the present invention is immunological regulation and growth promoting function biologic product effective, easy to use with bacterium peptide immunological regulation feed addictive.
Embodiment 2, the pig preparation of bacterium peptide immunological regulation feed addictive
Take bacillus amyloliquefaciens SC06 (10 9cfu/g) 40 kilograms, bacterium powder, 10 kilograms, Pidotimod pulvis (purity more than 99%), zeolite powder 30 kilograms, cornstarch 20 kilograms; Be packed as 1 kilogram of packaging after abundant mixing, can use.
Embodiment 3, the pig preparation of bacterium peptide immunological regulation feed addictive
Take bacillus amyloliquefaciens SC06 (10 9cfu/g) 10 kilograms, bacterium powder, 10 kilograms, Pidotimod pulvis (purity more than 99%), zeolite powder 30 kilograms, cornstarch 50 kilograms; Be packed as 1 kilogram of packaging after abundant mixing, can use.
Following experimental group is set:
Test 4 (T4): the basal diet of interpolation 0.06% pig bacterium peptide immunological regulation feed addictive (embodiment 2) of feeding.
Test 5 (T5): the basal diet of interpolation 0.15% pig bacterium peptide immunological regulation feed addictive (embodiment 3) of feeding.
That is, the same T3 of consumption of above-mentioned T4, T5 active ingredient.
All the other detect as above-mentioned experiment.Acquired results is as described in following table 4 ~ table 6.
From growth test, the weight average that increases day by day of test 4 and test 5 is significantly higher than control group, but lower than test 3.
Table 4 is on the impact of piglet growth
Table 5 is on the impact of piglet ileal mucous membrane gene expression
From ileum gene expression, test 4 pro-inflammation genes IL-6 and IL-8 higher than control group and test 5 and test 3, and press down scorching gene IL-10 higher than control group but lower than test 5 and test 3, and it is minimum in three test group to test 5 pro-inflammation genes, anti-inflammation gene is the highest in three test group; And the gene expression testing 3 is between test 4 and test 5, the best proinflammatory and anti inflammatory immunity of tool balances.
Table 6 is on the impact of piglet Cytokine of Serum content
From piglet Cytokine of Serum containing taking temperature, test 3 proinflammatory cytokine IFN-γ and IL-6 and anti-inflammatory cytokines IL-4 and IL-10 also between test 4 and test 5, the proinflammatory and anti inflammatory immunity balance that therefore tool is best.
Finally, it is also to be noted that what enumerate above is only several specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be had.All distortion that those of ordinary skill in the art can directly derive from content disclosed by the invention or associate, all should think protection scope of the present invention.

Claims (2)

1. pig bacterium peptide immunological regulation feed addictive, is characterized in that being made up of the component of following weight portion: concentration is 10 9bacillus amyloliquefaciens SC061-5 part of cfu/g, Pidotimod 1 part, zeolite powder 3 parts, cornstarch 5-1 part.
2. pig according to claim 1 bacterium peptide immunological regulation feed addictive, is characterized in that being made up of the component of following weight portion: concentration is 10 9bacillus amyloliquefaciens SC062 part of cfu/g, Pidotimod 1 part, zeolite powder 3 parts, cornstarch 4 parts.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004016098A1 (en) * 2002-08-14 2004-02-26 Novozymes A/S Feed composition and method of feeding animals
CN103045498A (en) * 2012-10-10 2013-04-17 浙江大学 Bacillus amyloliquefaciens and application thereof
CN103182067A (en) * 2011-12-30 2013-07-03 齐鲁动物保健品有限公司 Application of pidotimod as immune enhancer on livestock and poultry
CN103981129A (en) * 2014-05-06 2014-08-13 武汉科前动物生物制品有限责任公司 Composite microbial preparation, and preparation method and application thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004016098A1 (en) * 2002-08-14 2004-02-26 Novozymes A/S Feed composition and method of feeding animals
CN103182067A (en) * 2011-12-30 2013-07-03 齐鲁动物保健品有限公司 Application of pidotimod as immune enhancer on livestock and poultry
CN103045498A (en) * 2012-10-10 2013-04-17 浙江大学 Bacillus amyloliquefaciens and application thereof
CN103981129A (en) * 2014-05-06 2014-08-13 武汉科前动物生物制品有限责任公司 Composite microbial preparation, and preparation method and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
郝生宏 等: "益生菌对宿主免疫功能的调节作用", 《饲料研究》 *

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