Deprecated: The each() function is deprecated. This message will be suppressed on further calls in /home/zhenxiangba/zhenxiangba.com/public_html/phproxy-improved-master/index.php on line 456
GB2158353A - Veterinary preparations - Google Patents
[go: Go Back, main page]

GB2158353A - Veterinary preparations - Google Patents

Veterinary preparations Download PDF

Info

Publication number
GB2158353A
GB2158353A GB08510673A GB8510673A GB2158353A GB 2158353 A GB2158353 A GB 2158353A GB 08510673 A GB08510673 A GB 08510673A GB 8510673 A GB8510673 A GB 8510673A GB 2158353 A GB2158353 A GB 2158353A
Authority
GB
United Kingdom
Prior art keywords
composition
acid
antiprotozoal
antibacterial
treatment
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
GB08510673A
Other versions
GB8510673D0 (en
Inventor
Dr Ferenc Simon
Dr Atilla Romvary
Dr Janos Varga
Dr Peter Laczay
Dr Laszlo Fodor
Edit Bruckner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
HAJDUSAGI AGRARIPARI EGYESULES
Original Assignee
HAJDUSAGI AGRARIPARI EGYESULES
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by HAJDUSAGI AGRARIPARI EGYESULES filed Critical HAJDUSAGI AGRARIPARI EGYESULES
Publication of GB8510673D0 publication Critical patent/GB8510673D0/en
Publication of GB2158353A publication Critical patent/GB2158353A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/265Esters, e.g. nitroglycerine, selenocyanates of carbonic, thiocarbonic, or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

Synergistic antibacterial-antiprotozoal drug compositions useful for the treatment of respiratory, gastrointestinal and urogenital infections of domestic animals comprises tiamulin hydrogen fumarate and microbiologically active organic acids, preferably oxolinic acid and nalidixic acid or a pharmaceutically acceptable water-soluble derivate thereof in a weight ratio of 1:5 to 5:1. The active components are admixed or diluted with a carrier used in veterinary therapy and formulated for oral or parenteral use.

Description

SPECIFICATION New drug compositions and process for their preparation The invention relates to new antibacterial and antiprotozoal drug compositions and a process for preparing same.
Oxolinic acid (5-ethyl-5, 8-dihydro-8-oxo-1, 3-dioxolo/4,5g/quinoline-7-carboxylic acid) and nalidixic acid (l-ethyl-l, 4-dihydro-7-methyl-4-oxo-1, 8-naphthyridine-3-carboxylic acid) are well known compounds in human medicine as well as in veterinary therapy. In the field of human medicine they are mainly used as urinary tract antiseptics. In veterinary therapy they are applied to fight infections caused by Gram-negative bacteria.
There are known combinations of oxolinic acid or nalidixic acid with antibiotics and other organic acids, too. Simultaneous application of oxolinic or nalidixic acid with trimethoprim was reported by Bartolini et al. [Bartolini et al., Drug. Exp. Clin. Res. 6, 311-316 (1980)].
Tiamulin (14-desoxy- 14-[(2-diethylamino-ethyl)-mercapto-acetoxy]-mutilin hydrogen fu ma rate) is a relatively new antibiotic in veterinary therapy. It is mainly used in the treatment of disorders of the repiratory and gastrointestinal tract of swine. It successfully cures swine dysentery and pneumonia caused by Mycoplasma [Burch et al., Vet. Rec. 10, 236-237 (1983)].
Tiamulin's effect on Gram-positive bacteria (Staphylococcus, Streptococcus), Mycoplasma and Treponema is described in British patent specification No. 2,027,590.
The range of tiamulin's activity against Gram-negative bacteria is relatively narrow according to microbiological test results (Forster, J. and Pickles, G., IPVS Congress, Zagreb, June 13-15, 1978).
It is the object of the present invention to produce drug combinations of known antibiotics which, beside considerable reduction of expenses, will exhibit the individual effect of two or more components in a synergistic way.
Now it has been found that when tiamulin hydrogen fumarate is applied together with antibacterial and antiprotozoal organic acids, preferably oxolinic acid and/or nalidixic acid, beside the curing characteristics of the individual compounds differing in range of activity (e.g.
in vitro inhibitory effect on Shreptococci and E. coli) distinct synergism can be observed against certain strains.
Based on these facts the invention relates to new drug compositions of synergistic effect useful for the treatment of respiratory, gastrointestinal and urogenital infections of domestic animals, comprising the antibiotic tiamulin hydrogen fumarate and antibacterial-antiprotozoal organic acids, preferably oxolinic acid or nalidixic acid, or a pharmaceutically acceptable watersoluble derivative thereof in a weight ratio of 1:5 to 5:1, admixed with inert, pharmaceutically acceptable solid or liquid carriers.
The invention relates also to a process for preparing a new synergistic antibacterialantiprotozoal composition useful for the treatment of respiratory, gastrointestinal and urogenital infections of domestic animals, which comprises admixing tiamulin hydrogen fumarate with an antibacterial-antiprotozoal organic acid, preferably oxolinic or nalidixic acid, or a pharmaceutically acceptable water-soluble salt thereof in a weight ratio of 5:1 to 1:5, and with inert, non toxic carriers used in veterinary therapy.
Microbiological tests were carried out to investigate the in vitro inhibitory effect of the active compounds against different strains of bacteria and to state their synergism. For better understanding, the same field isolates of pathogens were used as test organisms. Minimal inhibiting concentrations (MIC) and minimal bactericide concentrations (MBC) of tiamulin and oxolinic or nalidixic acid were determined. The results are shown in Tables I and II. The MIC and MBC values were measured in yg/ml units.
Table I Intensification of the Antibacterial Activity of the 1:1 Ratio by Weight Combination of Tiamulin and Oxolinic Acid Test Organism Tiamulin Oxolinic Acid Combination Grade of MIC MBC MIC MBC MIC MBC Intensification Staphylococcus aureus 25 100 25 50 5 25 4 - 10x ------------------------------------------------------------------------------------------------------------ Listeria monocytogenes 50 100 100 100 5 25 8 - 40x ------------------------------------------------------------------------------------------------------------- Salmonells typhi-murium 200 200 1 10 1 1 2 - 400x -------------------------------------------------------------------------------------------------------------- Klebsiella pneumonise 200 200 5 10 5 5 2 - 80x Table II Intensification of the Antibacterial Activity of the 1::1 Ratio by Weight Combination of Tiamulin and Nalidixic Acid Test Organism Tiamulin Nalidixic Acid Combination Grade of Inten MIC MBC MIC MBC MIC MBC sification Staphylococcus aureus 25 100 5 200 5 5 4 - 80x ------------------------------------------------------------------------------------------------------------ Listeria monocytogenes 50 100 200 200 50 100 8 - 8x ------------------------------------------------------------------------------------------------------------- Salmonells typhi-murium 200 200 10 10 10 10 2 - 40x -------------------------------------------------------------------------------------------------------------- Klebsiella pneumonise 200 200 50 50 50 50 2 - Bx The in vitro tests prove the synergistic effect of the combination against certain strains of bacteria.The intensification of the effect is clearly shown against Staphylococcus aureus, Listeria monocytogenes, Klebsiella pneumoniae and Salmonella typhi-murium. The grade of intensification is 2 to 8 times in the average, but it can reach even the 400 times level.
Because of their synergistic properties, the preparations of the invention may be applied in lower and more economic doses. As a result of the broadened range of spectrum, the combinations can be successfully used in the therapy of respiratory and other diseases owing to mycoplasma and secondary bacterial complications.
Further advantage of the combinations according to the invention is the reduced possibility of development of toxic side-effects and the shortening of the necessary withdrawal period to prevent drug residues in edible tissues. These advantages originate from the reduced doses of the active components in the combinations.
The preparations of the invention can be produced according to known technics, that is the active ingredients are mixed with or dissolved in carriers used in veterinary therapy.
The formulation of the preparate is chosen according to the given case. It may be applied orally, mixed to the feed or in drinking water, mainly in large scale units, or parenterally for individual or mass treatment.
The parenteral application may be intra-muscular, intrauterin or intracysternal. The preparation for parental use is spread on a carrier, preferably lactose, in 1:1 to 1:50 ratio by weight, and then it is dissolved in a suitable solvent, preferably water, dimethyl formamid or vegetable oil, in a 1:1 to 1:25 ratio by weight.
Favourable effects can be reached with the synergistic drug compositions of the invention in case of enteritis due to Salmonella, Klebsiella and E. coli strains; -metritis caused by Proteus, E. coli, Streptococcus, Staphylococcus strains; -mastitis caused by Streptococcus, Staphylococcus, E. coli, Klebsiella and Mycoplasma strains of cattle, calves and dogs; iseases of the digestive and respiratory organs of swine (e.g. E. coli diarrhoea, swine dysentery, pneumonia caused by Mycoplasma); ---diseases of the digestive and respiratory organs of rabbits and poultry (E. coli infections, etc.).
The proposed oral dose of the water-soluble preparation containing 60.0% by weight of active ingredient is -in case of enteritis 400 mg/animal/day for calves 350 mg/liter for piglets -in case of enteritis and urinary infections 200-400 mg/animal/day for dogs.
When the feed is medicated with a premix containing 60.0% of active ingredient, the recommanded dose for a continuous five-day treatment is -in case of infections of the digestive and respiratory organs and swine dysentery 200-400 mg/kg feed for swine -in case of infections of the digestive and respiratory organs 150-250 mg/kg feed for rabbits and 300-400 mg/kg feed for poultry.
For intrauterinal use a daily dose of 5.0g of the mixture containing 60% of active ingredients in capsules is proposed.
The use of the preparations of the invention is not limited against the pathogens or to the treatment of species listed above or in the following examples.
Example 1 1.5 g of tiamulin hydrogen fumarate, 1.5 g of oxolinic acid and 2.0 g of lactose are admixed and filled into an intrauterine capsule. 24 cows were treated intrauterinally with these capsules immediately after calving for 3 consecutive days. Involution quickened, metritis and retention of placenta did not develop. Bacterial infections were prevented by the treatment.
Example 2 0.6 g of tiamulin hydrogen fumarate, 3.0 g of nalidixic acid and 1.4 9 of lactose are admixed. The preparation is suspended in 100 ml of water.
50 piglets of 5 litters were treated orally with 1.0 ml of the suspension. Clinical symptoms disappeared in all of the animals after the first treatment. New cases or relapse did not occur.
Example 3 10.0 g of tiamulin hydrogen fumarate and 2.0 g of oxolinic acid are suspended in 1 00.0 ml of oil for injection.
10 ml of this suspension was infused intracysternally via the teat canal of 5 mastitic cows.
The symptoms of acute inflammations (swollen and warm udder, macroscopic change of the milk secreted etc.) considerably abated after the first treatment. Bacteriological tests carried out a week after the third treatment gave fully negative results.

Claims (9)

1. A synergistic antibacterial-antiprotozoal drug composition useful for the treatment of diseases of respiratory, gastrointestinal and urogenital infections of domestic animals, comprising tiamulin hydrogen fumarate and antibacterial-antiprotozoal organic acids or a pharmaceutically acceptable water-soluble derivative thereof in a weight ratio of 1:5 to 5:1 admixed with inert, non-toxic solid or liquid carriers used in veterinary therapy.
2. A composition as claimed in claim 1, in which the organic acid is oxolinic acid or nalidixic acid.
3. A composition as claimed in claim 1 for oral administration, comprising the active ingredients in a dose of 5-1 5 mg/kg body weight.
4.. A composition as claimed in claim 1, wherein the carrier is lactose.
5. A composition as claimed in claim 4 for intrauterinal application, comprising the active ingredients in a ratio of 60% by weight of the mixture filled in capsule in a daily dose of 5.0 g/animal.
6. A composition as claimed in claim 1, wherein the carrier is purified and sterile vegetable oil acceptable in veterinary therapy.
7. A composition as claimed in claim 6 for intracysternal application, comprising the active ingredients in a quantity of 0.2 to 2.0 g/quarter of udder.
8. A process for preparing a new synergistic antibacterial-antiprotozoal composition useful for the treatment of respiratory, gastrointestinal and urogenital infection of domestic animals, which comprises admixing tiamulin hydrogen fumarate with an antibacterial-antiprotozoal organic acid or a pharmaceutically acceptable water-soluble salt thereof in a weight ratio of 5:1 to 1:5, and with inert, non toxic carriers used in veterinary therapy.
9. A process as claimed in claim 8, wherein oxolinic or nalixidic acid is used as organic acid.
GB08510673A 1984-04-28 1985-04-26 Veterinary preparations Withdrawn GB2158353A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
HU841681A HU192982B (en) 1984-04-28 1984-04-28 Process for producing synergetic pharmaceutical compositions containing thiamulin and antibacterial and antiprotozoal organic acids

Publications (2)

Publication Number Publication Date
GB8510673D0 GB8510673D0 (en) 1985-06-05
GB2158353A true GB2158353A (en) 1985-11-13

Family

ID=10955659

Family Applications (1)

Application Number Title Priority Date Filing Date
GB08510673A Withdrawn GB2158353A (en) 1984-04-28 1985-04-26 Veterinary preparations

Country Status (11)

Country Link
AT (1) AT388669B (en)
BE (1) BE902250A (en)
CH (1) CH666407A5 (en)
DE (1) DE3515185A1 (en)
ES (1) ES8607333A1 (en)
GB (1) GB2158353A (en)
HU (1) HU192982B (en)
IT (1) IT1200461B (en)
LU (1) LU85870A1 (en)
NL (1) NL8501061A (en)
SE (1) SE8502038L (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4041563A1 (en) * 1990-12-22 1992-06-25 Sanol Arznei Schwarz Gmbh METHOD FOR PRODUCING ACTIVE MICROPARTICLES FROM HYDROLYTICALLY DEGRADABLE POLYMERS

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2027590A (en) * 1978-08-14 1980-02-27 Squibb & Sons Inc Parenteral compositions containing tiamulin
GB2035800A (en) * 1978-10-20 1980-06-25 Ausonia Farma Srl Pharmaceutical compositions containing anantibiotic and a beta ketoacid

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1208279A (en) * 1967-05-12 1970-10-14 Ici Ltd Veterinary compositions containing 4-hydroxy-1,8-naphthyridine derivatives
GB2072012B (en) * 1980-03-14 1984-07-25 Squibb & Sons Inc Veterinary compositions containing pleuromutilin derivatives

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2027590A (en) * 1978-08-14 1980-02-27 Squibb & Sons Inc Parenteral compositions containing tiamulin
GB2035800A (en) * 1978-10-20 1980-06-25 Ausonia Farma Srl Pharmaceutical compositions containing anantibiotic and a beta ketoacid

Also Published As

Publication number Publication date
CH666407A5 (en) 1988-07-29
NL8501061A (en) 1985-11-18
GB8510673D0 (en) 1985-06-05
SE8502038L (en) 1985-10-29
AT388669B (en) 1989-08-10
ATA122985A (en) 1989-01-15
BE902250A (en) 1985-10-22
ES542610A0 (en) 1986-05-16
LU85870A1 (en) 1986-11-05
ES8607333A1 (en) 1986-05-16
HUT37347A (en) 1985-12-28
IT8520515A0 (en) 1985-04-26
HU192982B (en) 1987-08-28
SE8502038D0 (en) 1985-04-26
IT1200461B (en) 1989-01-18
DE3515185A1 (en) 1985-11-07

Similar Documents

Publication Publication Date Title
KR100919725B1 (en) Composition for treatment and prophylaxis of diseases and infections of poultry
HU203667B (en) Process for producing synergetic zootechnical compositions containing three components
CN101530475A (en) Application of macleaya cordata extract in veterinary drugs for economic animals
US4650790A (en) Drug combinations having synergistic effect
WO2007117102A1 (en) Complex antibiotic composition for bovine mastitis
KR100438209B1 (en) Complex antimicrobial composition based on carvacrol, thymol, and citral
JP2002507123A (en) Method for improving the effectiveness of probiotics, preparation of nutritional additives and animal feed containing same
GB2158353A (en) Veterinary preparations
AU652443B2 (en) Treatment of mastitis
EP0597167B1 (en) Veterinary preparation containing an antibiotic mixture of gentamicin and lincomycin as an additive to drinking water or animal feed and its use in pig breeding
AU606330B2 (en) Sulphonamide /diaminopyrimidine compositions for the treatment of microbial infections
US4404189A (en) Synergistic antimicrobial compositions
KR950009945B1 (en) "veterinary preparation containing an antibiotic mixture of gentamicin and lincomycin as an additive to drinking water or animal feed and its use in pig breeding
HU207445B (en) Method for producing preparation and fodder mixture of synergetical effect suitable for medicinal treatment of bacterial sicknesses of domestic animals
JPH11116474A (en) Antibacterial combination
HU190963B (en) Process for production of synergyc medical preparatives containing organic acids with oxitetracylin and antimicrobatic influence
FR2563432A1 (en) New antibacterial and antiprotozoal pharmaceutical compositions comprising tiamulin acid fumarate and process for preparing them
US3546207A (en) Neomycin citrate
HU201668B (en) Method for producing veterinary preparation and fodder premixture of synergetic effect serving for making more economical breeding of animals
CA1211643A (en) Synergic growth-promoting feed supplement composition for farm animals
RU1826904C (en) Method for prophylaxis and treatment of bartonellosis at calves
HU191399B (en) Process for the production of new compound medicine of synergic effect
JPH0291026A (en) Method for preventing and treating liver tumor of animal and animal feed composition
JPH06128163A (en) Agent for preventing or treating fish streptococcosis with mixed ingredients
HU226731B1 (en) Synergetic veterinay composition containing a combination of fluoroquinolone and colistin for the inhibition of fluoroquinolone-resistance

Legal Events

Date Code Title Description
WAP Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1)