WO2017010856A1 - Composition pour un traitement de la mammite subclinique des vaches - Google Patents

Composition pour un traitement de la mammite subclinique des vaches Download PDF

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Publication number
WO2017010856A1
WO2017010856A1 PCT/LV2015/000005 LV2015000005W WO2017010856A1 WO 2017010856 A1 WO2017010856 A1 WO 2017010856A1 LV 2015000005 W LV2015000005 W LV 2015000005W WO 2017010856 A1 WO2017010856 A1 WO 2017010856A1
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Prior art keywords
composition
milk
cows
glycopeptides
treatment
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PCT/LV2015/000005
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English (en)
Inventor
Jevgeņijs JERMOLAJEVS
Lilija PEŠKOVA
Gundega GULBE
Vaira SAULĪTE
Simona DONIŅA
Anda VALDOVSKA
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Rīgas Stradiņa Universitāte
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Publication of WO2017010856A1 publication Critical patent/WO2017010856A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01017—Lysozyme (3.2.1.17)

Definitions

  • the invention relates to veterinary medicine and biotechnology, especially with new, natural composition development for the treatment of subclinical mastitis in cows.
  • Mastitis is inflammation of the mammary gland parenchyma.
  • the subclinical mastitis is not observed visible pathological udder changes (no clinically detectable), but milk is microscopically changed or containing bacteria and other inflammatory products, therefore undergoing a major leukocytes and amount of pro-inflammatory cytokine release [1 ].
  • An important indicator of subclinical mastitis is changes in number of somatic cell in milk. Regulation (EC) No.
  • subclinical mastitis in the herd determines at least 75% of the animals [3] and its formation is promoted by several factors -the keeping of animals, nutrition, animal immune system status and udder tissue microorganisms induced an inflammatory reaction.
  • the literature is referred to Streptococcus agalactiae, Staphylococcus aureus and other gram-positive coccus, especially Streptococcus dysgalactiae, Streptococcus uberis, enterococcus, coagulase negative staphylococcus, including S. hyicus, S. epidermidis, S. xylosus and S. intermedius [3] ⁇
  • Mastitis in cows is a serious livestock farming problem, because of this disease depends on the quality of milk products and harmlessness.
  • the acute forms of mastitis in cows can be determined according to the following external features: udder is swollen, hot and painful. The animal's body temperature increase, in milk appears of proteins clots. However, 90-95% of cases mastitis conducted subclinical (of chronic) form, which is characterized by signs of allergy - mammary gland inflammation takes place invisibly, milk visually looks a normal. For the determination of subclinical mastitis, udder quarter of milk to realize of somatic cell count calculation and to realize of microflora analysis. Mastitis treatment directed to elimination of infection and increase of immunity.
  • synthetic antibacterial and chemotherapeutic preparations therapy use acceptable only in exceptional cases, because synthetic antibacterial agents containing milk cases is not harmless to human health.
  • a synthetic antibacterial and chemotherapeutic preparation, which remains in milk, can create irregularities of milk products manufacturing technology. The special caution should be observed using medical products, designed into tire teat canal (intracisternal), because it can cause for people allergic reaction and worsen the course of the disease.
  • an antimicrobial substance anavidine [8], pine needle extract [9], guanidine [10] in the development of an antimicrobial polymer film, which is applied on the cow udder teats, is known.
  • the film prevents penetration of microflora into the teat canal and contributes to softening the skin of the teat ends.
  • phytotherapeutic preparations should be lasting, it can affect the organoleptic properties of milk.
  • the objective of the invention is:
  • composition consisting of the lactic acid, lysozyme, glycopeptides and natural saline solution. Furthermore, the composition contains the lactic acid, lysozyme, glycopeptides and 0.15M NaCl solution with the following component - mass ratio factors (mg):
  • composition contains glycopeptides derived from Lactobacillus spp.
  • Lactic acid is a oxypropan acid, chemical formula C3 ⁇ 4CH (OH)COOH or C 3 H 6 0 3 . It is formed in the process of sugar lactic acid fermentation in sour milk, wine and beer fermentation process. In human and animal body the lactic acid is formed by decay of glucose - main source of body carbohydrates, thereby providing energy for a number of chemical reactions in a body. In food industry the lactic acid is used as a preservative, food additive E270 [11].
  • Lysozyme belongs to the hydrolases enzymatic class that destroys the bacterial cell walls (murein) with the help of peptidoglycan hydrolysis. Lysozyme is derived from hen's egg albumen. The enzyme is present both in human and animal organisms: in mucous membrane of the gastrointestinal tract, lachrymal fluid, saliva. Lysozyme exhibits antibacterial properties [12]. Lysozyme is used in a form of suppositorium for the preparation of antifungal agents intended for children [13], in the preparation of eye drop composition for eye infection treatment [14].
  • Glycopeptides Glycopeptides.
  • Known synthetic glycopeptides vancomycin, teicoplanin, glyburide
  • application of synthetic glycopeptides can cause increase of histamine level in blood and various allergic reactions.
  • natural glycopeptides which do not cause side- effects, they are derived from lactic acid bacteria, mostly from Lactobacillus spp [15].
  • Natural glycopeptides exhibit also antibacterial properties as to septic infections caused by microbes and viruses [16].
  • Natural glycopeptides exhibit antiviral and immunomodulatory properties, which are used in the production of biological food additives containing colostrum [17].
  • component dosage was, respectively, lower than 200 mg (lactic acid), 100 mg (lysozyme) and 2 mg (glycopeptides), a desired antimicrobial effect was not achieved.
  • the antimicrobial activity of solution of the 1 st example composition is tested by applying the pit -patterned diffusion method [18, 19].
  • Bacterial culture is prepared in peptone salt solution in concentration 1.5x10 s CFU/ml (0.5 McFarland).
  • 0.1 ml of bacterial culture is put into sterile 100 mm Petri Dish and poured over with 20 ml Miiller Hinton Agar.
  • a pit is developed in agar (6 mm 0) and is filled with 60 ⁇ of tested first composition solution.
  • the dishes are prepared in triplicates, incubated for 24 hours at 37 °C followed by measuring zone diameters of bacterial growth inhibition (or antagonistic activities). Results of in vitro are shown in Table 1.
  • composition content as per 10 ml of natural saline solution consisting of 500 mg lactic acid, 300 mg lysozyme and 10 mg glycopeptides.
  • the tested composition which consists of 500 mg lactic acid, 300 mg lysozyme and 10 mg glycopeptides, in vitro manifests 18-20 mm - scale inhibition against all tested bacterial cultures ⁇ S. saprophyticus, S. haemolyticus. S. aureus. E. coli, S. liquefaciens and C.freundii), which means that this composition exhibits active antagonistic properties against causative agents of mastitis.
  • Example 2 Components of the solution in Example 2 were as follows: 200 mg lactic acid, 100 mg lysozyme and 2 mg glycopeptides, and which was prepared similarly as that referred to in example 1. The results in vitro of antimicrobial activity are shown in Table 2. Table 2
  • composition content as per 10 ml of natural saline solution consisting of 200 mg lactic acid, 100 mg lysozyme and 2 mg glycopeptides.
  • the tested composition which consists of 200 mg lactic acid, 100 mg lysozyme and 2 mg glycopeptides, in vitro manifests 8-14 mm - scale inhibition against all tested bacterial cultures, which means that this composition exhibits active antagonistic properties against causative agents of mastitis, but they are lower than in the first example, where the components were in a larger concentration.
  • the solution haemolytic activity and sterility were tested on blood agar, which contained 50 g ⁇ 1 bovine blood.
  • the tested solution is applied strip-wise on blood agar, allowed to incubate for 24 hours at 37 °C and by determining haemolysis - ⁇ -haemolysis (clear and transparent around the colonies), a- haemolysis (greenish zone around the colonies) or ⁇ - haemolysis (non-haemolytic) [1,17]. None of the tested solutions exhibited haemolysis on blood agar ( ⁇ - haemolysis), and they were sterile.
  • cows were selected with the increased somatic cell count in milk in the anamnesis.
  • the cows were divided into 2 groups, i.e., per 5 cows in each group.
  • 10 ml of sterile 0.9% NaCl solution had been administered to 5 cows of the control group (20 quarters) intramammary in each quarter - 1 time a day after milking, 3 times once every 48 hours.
  • 10 ml of sterile, new composition infusion intended for treatment of subclinical mastitis had been administered to 5 cows of the experimental group (20 quarters) - 1 time a day after milking, 3 times once every 48 hours.
  • the composition content 10 ml natural saline solution, 500 mg lactic acid, 300 mg lysozyme and 10 mg glycopeptides.
  • the composition was prepared according to the technique described in the 1 st example.
  • the total bacterial count, somatic cell count in milk and milk quality indices were determined in the beginning of the experiment (1 st day), 3 days, 5 days, 7 days and 14 days after the first administration of the preparation.
  • the total bacterial count in the affected by mastitis udder quarters (Refer to Table 3) (SCC on the 1 st day 2000 thousand/ml and higher) after the composition administration significantly reduced, i.e., from 3167 thousand/ml on the 1 st day to 55 thousand/ml on the 3 rd day and to 7 thousand/ml on the 14 th day.
  • SCC somatic cell count
  • Somatic cell count is the key indicator that allows judging the quality of milk produced by the secretion of the mammary gland [2].
  • the somatic cell count drastic gain is frequently observed, which evidences a positive immunogenic response of an animal body. Usually over a few days SCC drops.
  • SCC initially was up to 2000 000 cells/ lml
  • SCC in experiment increased and on the 14 th day it was 3.1-4.2 times higher than on the 1 st day.
  • Fat content Initially average milk fat content in the experimental group was 1.83 % and in the control group - 1.88 %. On the 3 rd day after testing of the preparation in the experimental group the fat content increased by 0.65 %, but in the control group it increased by 0.11 %. In cows of the experimental group on the 7 th day milk fat content was 1.86 %, but in the control group - 2.12 %. Conclusion: Application of the composition does not cause significant changes in milk fat content.
  • Lactose content Initially average milk lactose content in the experimental group was 4.57 % and in the control group - 4.16 %. On the 3 rd day after testing of the preparation in the experimental group lactose content reduced by 0.65 %, but in the control group it reduced by 0.12 %. In the experimental group on the 7 th day milk lactose content was 4.14 %, but in the control group - 4.19 %. Conclusion: Application of the composition does not cause significant changes in milk lactose content.
  • Pathogenic microorganism count in the experimental group was determined on 20 quarters of subclinical mastitis udder (5 cows) and on healthy udder 20 quarters of the control group (5 cows).
  • composition does not cause any significant changes in milk quality, i.e., milk fat, protein and lactose content.
  • the solution composition is designed for treatment of subclinical mastitis in cows, put up in an injector - 10.0 ml.
  • the composition is intended for administration into udder of lactating cows for treatment of subclinical mastitis caused by microorganisms of Staphylococcus spp., Streptococcus spp., Enterobacteriaceae family.
  • Administration is intended after milking (in the morning or evening) - 3 times once every 48 hours.
  • the content of one injector (10.0 ml) is administered into each udder quarter affected by mastitis after swiping the teat end with disinfectant. Withdrawal period: for meat and by-products - zero days, for milk - zero hours.
  • the clots can develop in milk, however, it does not cause changes to the total milk consistency.
  • Pat. RU 2537143, CI, 2014, A61 36/48; A61K31/41.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pregnancy & Childbirth (AREA)
  • Reproductive Health (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Endocrinology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Inorganic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention se rapporte à la médecine vétérinaire et à la biotechnologie, en particulier avec le développement d'une nouvelle composition naturelle pour le traitement de la mammite subclinique chez les vaches. L'invention a pour objet de créer les compositions efficaces pour le traitement de la mammite subclinique chez les vaches, qui peut fournir une qualité et une sécurité de produit laitier, qui n'est pas nécessaire pour la fabrication d'agents antibactériens de synthèse. L'objectif est atteint par développement d'une nouvelle composition, qui contient de l'acide lactique, le lysozyme, des glycopeptides et une solution physiologique de NaCl 0,15 M.
PCT/LV2015/000005 2015-07-14 2015-08-19 Composition pour un traitement de la mammite subclinique des vaches WO2017010856A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
LVP-15-67A LV15071B (lv) 2015-07-14 2015-07-14 Kompozīcija subklīniska mastīta ārstēšanai govīm
LVP-15-67 2015-07-14

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WO2017010856A1 true WO2017010856A1 (fr) 2017-01-19

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110376366A (zh) * 2019-07-19 2019-10-25 吉林大学 一种烟酸通过gpr109a受体应用于治疗奶牛乳腺炎的实验方法
CN110607324A (zh) * 2019-10-25 2019-12-24 扬州大学 奶牛溶菌酶基因乳腺特异性表达重组质粒及其构建方法和应用
RU2745236C1 (ru) * 2020-04-03 2021-03-22 Федеральное государственное бюджетное образовательное учреждение высшего образования "Кубанский государственный аграрный университет имени И.Т. Трубилина" Способ лечения и профилактики субклинического мастита у коров

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LV10054A (lv) * 1988-05-26 1994-05-10 Nika Health Products Ltd Pretvirusu antibakterials savienojums un lietosanas metode
RU2304167C2 (ru) * 2005-09-15 2007-08-10 Общество с ограниченной ответственностью "МЕДБИОФАРМ-БИОТЕХ" Способ получения гликопептидов и гликопептидный продукт, полученный этим способом, для использования в медицине
RU2319508C2 (ru) * 2003-07-31 2008-03-20 ФАРМАЦИЯ ЭНД АПДЖОН КОМПАНИ ЭлЭлСи Диспергируемый препарат противовоспалительного агента
KZ23357A4 (en) * 2010-06-14 2010-12-15 Orazbekovich Tagayev Orinbay Method on premilking dug washing

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LV10054A (lv) * 1988-05-26 1994-05-10 Nika Health Products Ltd Pretvirusu antibakterials savienojums un lietosanas metode
RU2319508C2 (ru) * 2003-07-31 2008-03-20 ФАРМАЦИЯ ЭНД АПДЖОН КОМПАНИ ЭлЭлСи Диспергируемый препарат противовоспалительного агента
RU2304167C2 (ru) * 2005-09-15 2007-08-10 Общество с ограниченной ответственностью "МЕДБИОФАРМ-БИОТЕХ" Способ получения гликопептидов и гликопептидный продукт, полученный этим способом, для использования в медицине
KZ23357A4 (en) * 2010-06-14 2010-12-15 Orazbekovich Tagayev Orinbay Method on premilking dug washing

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110376366A (zh) * 2019-07-19 2019-10-25 吉林大学 一种烟酸通过gpr109a受体应用于治疗奶牛乳腺炎的实验方法
CN110607324A (zh) * 2019-10-25 2019-12-24 扬州大学 奶牛溶菌酶基因乳腺特异性表达重组质粒及其构建方法和应用
RU2745236C1 (ru) * 2020-04-03 2021-03-22 Федеральное государственное бюджетное образовательное учреждение высшего образования "Кубанский государственный аграрный университет имени И.Т. Трубилина" Способ лечения и профилактики субклинического мастита у коров

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LV15071A (lv) 2015-11-20

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