• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention relates to a composition for preventing or treating infections contracted by hatchlings of farmed mammals, said composition comprising a mixture of bacterial strains, said composition being applied to the perineum and / or the udder or breasts. .
    公开号:FR3073140A1
    申请号:FR1760496
    申请日:2017-11-08
    公开日:2019-05-10
    发明作者:Michel Layus；Alexandre Brame
    申请人:Nolivade SARL；
    IPC主号:
    专利说明:

    Composition for improving the health of farm animals
    The invention relates to a composition for improving the health of animals, in particular farmed mammals.
    Mammals are born with a sterile digestive tract. The appearance of the intestinal flora therefore depends essentially on the environment and the physiological characteristics of each species. Under these conditions, it is the colostrum ingested during the first days of life that will in principle protect the newborn against digestive infections. This protection is only possible if the maternal colostrum is itself qualitatively and quantitatively adapted and appropriate.
    Breast immune protection takes as its starting point an intestinal immune process which inevitably impacts the establishment of this immunity. This results in the possible appearance of neonatal infections in young mammals from the 24th or 48th hour of life, due to insufficient protection and this until the 21st day, date of appearance of local immunity.
    The animal feed industry is increasingly seen as having a role to play in ensuring the responsible use of food antimicrobials in animal production. Policymakers ask feed producers, farmers, veterinarians and regulators to work together to determine best animal husbandry and hygiene practices and viable alternatives to reduce the use of antibiotics in farm animals and improve animal welfare.
    To meet the new requirements of modern agriculture, and taking into account the biological constraints of mammals, it is necessary to develop a method of protecting the breeding environment and the intestinal flora of newborns.
    The prior art provides applications on the udders of females for the purpose of treating mastitis, for example application RU2612009. However, these methods are intended to treat the udders of females, but are not intended to improve the health of newborns.
    Other methods known in the art aim to treat the rearing environment of newborn babies in order to promote their growth and well-being.
    Despite these attempts, the need to propose an improvement in conditions favorable to the good development of newborns remains.
    The invention aims to remedy this lack.
    An object of the invention is to provide a method for preventing health risks and improving the performance of mammalian farming, as well as a microbial composition.
    Also, the invention relates to a composition comprising or consisting essentially of a mixture:
    at. at least one strain of bacteria of the genus Bacillus, in particular a strain of
    Bacillus subtilis, and
    b. at least one strain of lactic acid bacteria, for its use in the context of the prevention or treatment of infections contracted by a newborn of farmed mammals at the time of birth, in particular digestive or respiratory infections, said composition being applied, on the perineum and / or on the udder (s) of the female going to give or having given birth to said newborn of farmed mammals, the application being carried out before and / or after parturition.
    The invention is based on the surprising observation made by the inventors that the combined use of at least one strain of lactic acid bacteria and at least one strain of Bacillus, when they are applied, before or after parturition, on the perineum and / or the udder (s) of females make it possible to protect, from an early age (from birth), newborns against infections harmful to their development, and thus promote and improve their growth.
    The composition as used in the invention has the advantage of having an action internal to the animal and to its external environment, making it possible to create a barrier flora from an early age.
    In the invention, by "udders and / or perineum" means that the application is made either on the perineum alone, or on one or more udders alone, or by combining applications on the perineum and at least on an udder , or even all the udders.
    Advantageously, in the invention, an application to the perineum can cover either an application to the perineum alone, or an intravaginal application, or an application both to the perineum and intravaginal.
    Advantageously, in the invention, an application to the udder (s) corresponds to an external application carried out on the udders of female mammals, but may also correspond to an intra mammary application of said udders of said female mammals.
    Intra-mammary applications are carried out by means, for example, of syringes introduced into the teat duct of the udders of said mammalian females. Those skilled in the art know the most suitable techniques for carrying out such intra-mammary applications.
    In the invention it is important that it is the female who gives birth to the newborn to be treated who receives the application of the above-mentioned composition. Indeed, the interest is that the new one as soon as it is expelled from the womb of the female is in contact with the treated perineum, and / or that its first feedings are made on a treated udder.
    By "at least one strain of bacteria of the genus Bacillus" is meant that one strain, or two strains, or three or more strains of Bacillus can be used in the context of the invention. Similarly, by "at least one strain of lactic acid bacteria" it is meant that one strain, or two strains, or three or more strains, can be used in the composition defined above.
    By strain of bacteria is meant in the invention all of the individuals (bacteria) resulting from successive subcultures of a bacterial colony.
    In other words, a strain is a part of a bacterial species different from other bacteria of the same species by a minor but identifiable difference. A strain is also defined as a population of bacteria that descends from a single organism or from the pure isolate culture. Strains of the same species can differ slightly from the other in many ways.
    The application to the perineum and / or the udder (s) is carried out under conditions where all or almost all of the parts are covered by the composition according to the invention. Indeed, it is not necessarily necessary that the treated part is completely covered, the main thing is that the amount of composition is sufficient for the newborn to be in contact with enough bacteria to protect it from infection.
    The application of the composition according to the invention being carried out before and / or after parturition, this means that
    - the composition is applied to the perineum, before, after or before and after parturition,
    - The composition is applied to the udder (s), before, after or before and after parturition, or
    - The composition is applied to the perineum and the udder (s), before, after or before and after parturition.
    The udder and / or perineum applications can be performed simultaneously, separately or spread over time.
    Advantageously, the invention relates to the composition for the above-mentioned use, in which the bacterial composition comprises:
    - at least one of the following three Bacillus subtilis strains: NOL01, NOL02, NOL03, said strains being deposited at the CNCM under the respective numbers: CNCM I - 4606, CNCM I-5043 and CNCM I - 4607, and
    - at least the strain of lactic bacteria: Lactococcus lactis spp lactis 1 strain NOL11, said strain being deposited at the CNCM under the number CNCM I -4609.
    The invention relates to the use of at least one strain chosen from the NOL01, NOL02 and NOL03 strains and at least the NOL11 strain. Also, the invention covers the following 7 combinations:
    - NOL01 and NOL11,
    - NOL02 and NOL11,
    - NOL03 and NOL11,
    - NOL01, NOL02andNOL11,
    - NOL01, NOL03andNOL11,
    - NOL02, NOL03 and NOL11, and
    - NOL01, NOL02, NOL03 and NOL11.
    All these strains were deposited in the national collection of microorganisms (CNCM) at the Pasteur Institute in Paris, according to the Budapest treaty.
    More advantageously, the invention relates to the composition for its use mentioned above, said composition comprising from 10 4 to 10 11 bacterial colonies of Bacillus and from 10 4 to 10 11 bacterial colonies of lactic bacteria, the bacterial colonies being per ml or g of composition .
    In other words, in this advantageous embodiment, if the composition according to the invention is in liquid form, said composition will comprise from 10 4 to 10 11 bacterial colonies of Bacillus per ml of composition and from 10 4 to 10 11 colonies lactic acid bacteria per ml of composition.
    If, on the other hand, the composition is in nonaqueous or even dehydrated form, said composition will comprise from 10 4 to 10 11 bacterial colonies of Bacillus per g of composition and from 10 4 to 10 11 bacterial colonies of lactic bacteria per g of composition.
    In the invention, from 10 4 to 10 11 bacterial colonies means: approximately 10 4 , approximately 5. 10 4 , approximately 10 5 , approximately 5.10 5 , approximately 10 6 , approximately 5.10 e , approximately 10 7 , approximately 5.10 7 , approximately 10 8 , approximately 5.10 8 , approximately 10 9 , approximately 5.10 9 , approximately 10 10 , approximately 5.10 10 or approximately 10 11 bacterial colonies.
    A particular application for the female mammal is 10 5 to 10 11 bacterial colonies per female, for each of the applications. That is to say that each bacterium will be present from 10 5 to 10 11 bacterial colonies per female for the perineum application, and from 10 5 to 10 11 bacterial colonies per female for the udder application.
    A person skilled in the art easily knows how to determine this number of bacteria, in particular by counting either manually (using a Malassez slide) or by using an automatic cell counter, or by dilution and then seeding on agar and counting of colonies.
    Even more advantageously, the invention relates to the use as defined above, where said at least one strain of Bacillus is in sporulated form and / or in vegetative form.
    Lactic acid bacteria are always in vegetative form. Also the composition according to the invention comprises at least one strain of Bacillus in sporulated form and at least one strain of lactic acid bacteria in vegetative form, or comprises at least one strain of Bacillus in vegetative form and at least one strain of lactic bacteria in form vegetative.
    Advantageously, the invention relates to a composition for its use as defined above, said composition being applied, on the perineum and / or on the udder (s) of the female going to give or having given birth to said newborn baby. farmed mammals, the application being carried out before and / or after parturition, said female being in an environment previously treated with said composition.
    In the invention, it is advantageous that before application to the udder (s) and / or the perineum of the females, the rearing environment of the said females is treated with the composition according to the invention before the said females are introduced. in said environment.
    Application in the environment makes it possible to control and / or orient the bacterial flora of the environment of the females by reducing the pathogenic pressure. It can be done by nebulization or spraying of livestock buildings, incorporation into the litter ... We observe less contamination of animals because there are fewer pathogenic foci. Such an application plays on living or surviving pathogens in the environment. The methods of spreading in the environment are spraying, nebulizing, covering the surfaces with foams or even dusting the composition powder according to the invention.
    Advantageously, the invention relates to the composition for the above-mentioned use, said composition consisting essentially of
    - the following three Bacillus subtilis strains: NOL01, NOL02, NOL03, said strains being deposited at the CNCM under the respective numbers: CNCM I - 4606, CNCM I-5043 and CNCM I - 4607, and
    - the lactic acid bacteria strain: Lactococcus lactis spp lactis 1 strain NOL11, said strain being deposited at the CNCM under the number CNCM I - 4609.
    It is particularly advantageous that the composition comprises the three strains of Bacillus subtilis bacteria mentioned above, in vegetative or sporulated form, and the lactic acid strain mentioned above, in vegetative form.
    Even more advantageously, the invention relates to the aforementioned composition for its aforementioned application, wherein said infections are intestinal infections in particular neonatal diarrhea, enteritis, salmonellosis, respiratory infections and in particular rhinitis, pasteurellosis, bordetellosis , skin infections and in particular ulcers, epidermitis, necrosis, and infections in the musculoskeletal system, especially infectious lameness.
    Indeed, the flora that constitutes the composition according to the invention, as illustrated in the examples below, will be ingested by the newborns and will make it possible to control and / or orient the flora present in the digestive systems and / or respiratory by reducing the existing or incoming pathogenic pressure (the digestive and respiratory systems being possible entry pathways for pathogens responsible for pathologies linked to other systems of the body). Another effect will be the stimulation of the animals' natural defenses. The flora also directly affects the digestive health of animals and limits the entry of other pathogens, which is advantageous as long as the newborn has not acquired its final immunity.
    Advantageously, the invention relates to the abovementioned use, where said composition is applied to the perineum and / or the udder (s) by spraying, spreading, dusting or soaking.
    Those skilled in the art, depending on the mode of application used, will be able to choose the most suitable material, and in particular will prefer a liquid composition for spraying or soaking and will favor a dehydrated composition for application by dusting.
    A method is also provided for preventing or treating infections contracted by a newborn of farmed mammals at the time of birth, in particular digestive infections, the method comprising a step of application to the perineum and / or to the udder (s) of the female going to give or having given birth to said newborn of farmed mammals, the application being carried out before and / or after parturition, of an effective dose of a composition comprising, or consisting of essentially in a mixture:
    at. at least one strain of bacteria of the genus Bacillus, in particular a strain of Bacillus subtilis, and
    b. at least one strain of lactic acid bacteria.
    In particular, there is provided a method as defined above, wherein said composition comprises
    - at least one of the following three Bacillus subtilis strains: NOL01, NOL02, NOL03, said strains being deposited at the CNCM under the respective numbers: CNCM I - 4606, CNCM I-5043 and CNCM I - 4607, and
    - at least the lactic acid bacteria strain: Lactococcus lactis spp lactis 1 strain NOL11, said strain being deposited at the CNCM under the number CNCM I - 4609, and in particular where said composition comprises
    - the following three Bacillus subtilis strains: NOL01, NOL02, NOL03, said strains being deposited at the CNCM under the respective numbers: CNCM I - 4606, CNCM I-5043 and CNCM I - 4607, and
    - the lactic acid bacteria strain: Lactococcus lactis spp lactis 1 strain NOL11, said strain being deposited at the CNCM under the number CNCM I - 4609.
    In the method described above, the amounts of bacteria mentioned above are applicable.
    The invention further relates to a kit for preventing digestive, respiratory or other infections of newborns of farmed mammals essentially comprising:
    - at least one composition as defined above, and
    - At least one means of applying said composition to the perineum and / or the udder or udders of the female having given or going to give birth to said newborn of farmed mammals.
    The kit according to the invention can consist of a predefined mixture of bacteria as defined above, or of several separate bottles or sachets comprising one or more bacterial strains according to the invention.
    The application means contained in the above-mentioned kit can be brushes for spreading application, cartridges to be used for spraying, a sprayer, a soaking tool or any other means allowing an application as defined above, in particular the spraying, spreading, dusting or soaking.
    The invention will be better understood and illustrated on reading the following examples and figures:
    BRIEF DESCRIPTION OF THE FIGURES
    Figure 1 is a graph showing the probability of occurrence of diarrhea in piglets in a pen, as a function of time (in days) after birth (t = 0), on batches 1 to 3 (curves A to C ) treated with an antibiotic, and lot 4, treated only with the composition according to the invention (curve D).
    Figure 2 is a graph showing the probability of mortality (excluding mortality eliminated "small") in piglets in a box, as a function of time (in days) after birth (t = 0), on lots 1 to 3 (curves A to C) treated with an antibiotic, and lot 4, treated only with the composition according to the invention (curve D).
    EXAMPLES
    Example 1
    The objective of this trial is to reduce the use of antibiotics in farms. This desire is accompanied by a strong investment in the development of all alternative solutions: vaccination, livestock management, biosecurity and substitution products ... Acting on the bacterial ecosystems that interact with animals is therefore a promising and the use of barrier flora is part of this approach.
    This trial shows the results obtained from a breeder already using barrier flora in peri-calving and who wished to re-evaluate his protocol (a new formulation of the barrier flora as well as a reduced application rate).
    Material and methods
    The breeding followed is a breeding of 700 sows breeder fattener in breeding selection (5 bands of 120 sows). The test was carried out on 2 strips within which 3 batches of 40 sows were made while respecting a homogeneous distribution of the rows of litter. The application protocol includes spraying the composition according to the invention into the environment, on the udders and perineum of sows as well as probiotic administration to sows via the soup machine.
    Table 1 summarizes the spraying protocols applied. All of the sows received a dose of probiotics from D-3 to D1 compared to parturition.
    Table 1: Flora spraying protocols
    Lot 1 - witness Lot 2 - witness Lot 3- witness Lot 4 test Application rate Former Former New light New light Formula Ancient News News News Bandaged 1 + 2 1 1 + 2 2 Antibiotic on piglets Yes Yes Yes no J-3 Environment Environment Environment Environment J-2 J-1 Udders and perineum Udders and perineum Udders and perineum Udders and perineum D0: Farrowing J1 Udders and perineum Udders and perineum Udders and perineum Udders and perineum J4 Udders and perineum Udders and perineum
    For lots 1 to 3, the farmer injected the piglets with antibiotics at the time of care, so these are control lots; he agreed to suspend this administration on part of the piglets corresponding to lot 4, so this is the test lot. Indeed, the antibiotic has an effect on the composition according to the invention and therefore cancels its potential effect. Lots 1 to 3 therefore represent the positive control lots (treated with antibiotics) and lot 4, the trial lot, represents an application on the udders and perineum.
    A daily recording is then carried out on the following criteria:
    - Faeces rating: 0 Normal, 1 Soft (degraded), 2 Dung, 3 Liquids,
    - Piglet cleanliness: 0 soiled <20%, 1 soiled between 20 and 50%, 2 soiled more than 50%
    - mortality and causes
    - treatments and reasons.
    Statistical analyzes were performed using R software (open source reference software; R Development Core Team (2008). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria). The model used is the logistics model.
    Results
    1) Diarrhea of piglets
    First, just after birth, the emergence of diarrhea in at least one piglet per case is assessed. The results are shown in Figure 1.
    Statistical modeling shows that the risk of the appearance of diarrhea in the newborn, in a box, is therefore significantly reduced in piglets having been in the presence of composition according to the invention applied to the perineum and the udders of their mother, compared to the same piglets treated with an antibiotic.
    The risk here is reduced by 50%.
    It should be noted that under lot 4, the farmer carried out 30% fewer drug treatments to care for the animals.
    2) Mortality of piglets
    Different causes of mortality have been identified: eliminated “small” (around 7% of piglets), mortality from digestive causes (around 2%), crushing mortality (around 2%) and other causes (around 4%).
    For the analysis of the results, the inventors did not retain the "eliminated small" cause, considering that it was not impacted by the application of the composition according to the invention in perished birth. The modeling represents the risk of mortality from all other causes at the scale of a box (Figure 2).
    The evolution of the risk of mortality in lot 4 is significantly different from the other 3 lots (p-value = 0.067).
    Discussion
    This study shows an equivalence of results between the two formulations and rates of application of barrier flora.
    Significant positive differences were highlighted with the protocol without injecting antibiotics into piglets on the onset of diarrhea and overall mortality. This improvement is linked to the lack of potential inhibition of the antibiotic on the flora.
    Conclusion
    The observations made on the batch without antibiotic clearly show the effectiveness on the health of the piglets (less diarrhea and mortality) of the composition according to the invention when the piglet is in contact immediately at birth with the composition according to the invention .
    权利要求:
    Claims (10)
    [1" id="c-fr-0001]
    claims
    1. Composition comprising or consisting essentially of a mixture:
    at. at least one strain of bacteria of the genus Bacillus, in particular a strain of Bacillus subtilis, and
    b. at least one strain of lactic acid bacteria, for its use in the context of the prevention or treatment of infections contracted by a newborn of farmed mammals at the time of birth, in particular digestive or respiratory infections, said composition being in a form suitable to be applied, on the perineum and / or on the udder (s) of the female going to give or having given birth to said newborn of farmed mammals,
    [2" id="c-fr-0002]
    2. Composition for its use according to claim 1, said composition being in a form suitable for application before and / or after parturition.
    [3" id="c-fr-0003]
    3. Composition for its use according to claim 1 or 2, in which the bacterial composition comprises:
    - at least one of the following three Bacillus subtilis strains: NOL01, NOL02, NOL03, said strains being deposited at the CNCM under the respective numbers: CNCM I - 4606, CNCM I-5043 and CNCM I - 4607, and
    - at least the strain of lactic bacteria: Lactococcus lactis spp lactis 1 strain NOL11, said strain being deposited at the CNCM under the number CNCM I - 4609.
    [4" id="c-fr-0004]
    4. Composition for its use according to any one of claims 1 to 3, said composition comprising from 10 4 to 10 11 bacterial colonies of Bacillus and from 10 4 to 10 11 bacterial colonies of lactic acid bacteria, the bacterial colonies being per ml or g of composition.
    [5" id="c-fr-0005]
    5. Composition for its use according to any one of claims 1 to 4, wherein said at least one strain of Bacillus is in sporulated form and / or in vegetative form.
    [6" id="c-fr-0006]
    6. Composition for its use according to any one of claims 1 to 5, said composition being in a form adapted to be applied, on the perineum and / or on the udder (s) of the female going to give or having given birth to said new - born of farmed mammals.
    [7" id="c-fr-0007]
    7. Composition for its use according to any one of Claims 1 to 6, said composition consisting essentially of
    - the following three Bacillus subtilis strains: NOL01, NOL02, NOL03, said strains being deposited at the CNCM under the respective numbers: CNCM I - 4606, CNCM I-5043 and CNCM I - 4607, and
    - the lactic acid bacteria strain: Lactococcus lactis spp lactis 1 strain NOL11, said strain being deposited at the CNCM under the number CNCM I - 4609.
    [8" id="c-fr-0008]
    8. Composition for its use according to any one of claims 1 to 7, wherein said infections are intestinal infections in particular neonatal diarrhea, enteritis, salmonellosis, respiratory infections and in particular rhinitis, pasteurellosis, bordetellosis, skin infections and in particular ulcers, epidermitis, necrosis, and infections in the musculoskeletal system, especially infectious lameness
    [9" id="c-fr-0009]
    9. A composition for use according to any one of claims 1 to 8, wherein said composition is in a form suitable to be applied to the perineum and / or the udder (s) by spraying, spreading, dusting or soaking.
    [10" id="c-fr-0010]
    10. Kit for the prevention of digestive, respiratory or other infections, of newborn mammals mainly comprising:
    - at least one composition according to any one of claims 1 to 9, and
    - At least one means of applying said composition to the perineum and / or the udder (s) of the female having given birth or going to give birth to said newborn of farmed mammals.
    类似技术:
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    同族专利:
    公开号 | 公开日
    WO2019092136A1|2019-05-16|
    US20200353019A1|2020-11-12|
    FR3073140B1|2021-04-30|
    EP3675886A1|2020-07-08|
    US11213554B2|2022-01-04|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    WO2013178947A1|2012-05-30|2013-12-05|Nolivade|Bacterial composition for the treatment of colibacillosis on farms, in particular poultry farms, and also drinking water containing such a bacterial composition|
    WO2014151837A1|2013-03-15|2014-09-25|Bayer Cropscience Lp|A bacillus subtilis strain for use in maintaining or improving the paw health of poultry|
    RU2546880C2|2013-06-03|2015-04-10|Федеральное государственное бюджетное учреждение науки Институт проблем экологии и эволюции им. А.Н. Северцова Академии Наук|Method of probiotic feed preparation for farm animals|
    RU2612009C1|2016-05-24|2017-03-01|Федеральное государственное бюджетное образовательное Учреждение высшего образования "Воронежский государственный аграрный университет имени императора Петра 1" |Method of treatment of subclinical mastitis in cows|
    FR3073140B1|2017-11-08|2021-04-30|Nolivade|COMPOSITION TO IMPROVE THE HEALTH OF LIVESTOCK|FR3073140B1|2017-11-08|2021-04-30|Nolivade|COMPOSITION TO IMPROVE THE HEALTH OF LIVESTOCK|
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    FR3110344A1|2020-05-20|2021-11-26|Nolivade|Decontamination process|
    法律状态:
    2019-05-10| PLSC| Publication of the preliminary search report|Effective date: 20190510 |
    2019-11-29| PLFP| Fee payment|Year of fee payment: 3 |
    2020-11-27| PLFP| Fee payment|Year of fee payment: 4 |
    2021-11-29| PLFP| Fee payment|Year of fee payment: 5 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1760496A|FR3073140B1|2017-11-08|2017-11-08|COMPOSITION TO IMPROVE THE HEALTH OF LIVESTOCK|
    FR1760496|2017-11-08|FR1760496A| FR3073140B1|2017-11-08|2017-11-08|COMPOSITION TO IMPROVE THE HEALTH OF LIVESTOCK|
    EP18807885.1A| EP3675886A1|2017-11-08|2018-11-08|Composition for improving the health of livestock|
    PCT/EP2018/080670| WO2019092136A1|2017-11-08|2018-11-08|Composition for improving the health of livestock|
    US16/762,278| US11213554B2|2017-11-08|2018-11-08|Composition for improving the health of livestock|
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