WO1992016209A1 - Granules and veterinary compositions comprising a water-soluble complex of flumequine - Google Patents

Granules and veterinary compositions comprising a water-soluble complex of flumequine Download PDF

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Publication number
WO1992016209A1
WO1992016209A1 PCT/HU1992/000013 HU9200013W WO9216209A1 WO 1992016209 A1 WO1992016209 A1 WO 1992016209A1 HU 9200013 W HU9200013 W HU 9200013W WO 9216209 A1 WO9216209 A1 WO 9216209A1
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WO
WIPO (PCT)
Prior art keywords
flumequine
weight
granules
water
granulation
Prior art date
Application number
PCT/HU1992/000013
Other languages
French (fr)
Inventor
István Hutás
Andrea HASZMANN-MÁRTON
Zoltán BENDE
Ferenc PRIBÉK
László NAGY
Original Assignee
Reanal Finomvegyszergyár
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
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Publication of WO1992016209A1 publication Critical patent/WO1992016209A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin

Definitions

  • the invention relates to granules comprising a water- soluble complex of flumequine, as .veil as to a process for the pre par it ion of such granules.
  • the invention also relates to veterinary compositions produced from the granules according to the invention.
  • flumequine (6,7-dihydro-9-fluoro-5-methyl-1-oxo-1H,5H-benzo-quinolysine-2-carboxylic acid) is an effective antimicrobial agent, highly active against various microorganisms, such as Aeromonas, Escherichia coli, Proteus, Klebsiella, Salmonella and Ihiterobacter species
  • Flumequine is, however, only spairingly soluble in water, which renders difficult to convert it into pharmaceutical and veterinary compositions and also restricts its therapeutic use. According to French patent No. 2,453,647 these, difficulties are overcome. by converting flumequine into pharmaceutical compositions in admixture with sodium carbonate; thus the resulting compositions comprise flumequine as its water-soluble sodium salt. According to the cited reference a water-soluble powder mixture comprising
  • flumequine 3-10.5 % by weight of flumequine can be prepared by admixing flumequine with sodium carbonate and lactose. Over these powders additional pharmaceutical compositions, such as tablets, injectable aqueous suspensions and ointments, are also mentioned in the cited reference; these composi tions are prepared by methods conventionally applied in pharmacotechnology.
  • these complexes are much more suitable for injection or oral administration than the known alkaline flumequine salts, and can be combined unrestrictedly with alkalisensitive substance s .
  • the granulation technique applied according to the invention ensures, on one hand, the homogeneity of the admixed components, and, on the other hand, provides the flumequine complex as a product easy to handle and particularly suitable for processing into a veterinary composition.
  • the invention relates to granules comprising a water-soluble complex of flumequine formed with polyvinyl pyrrolidone, an amino acid monomer or polymer containing basic group (s) or urea.
  • flumequine is admixed with 5-55 % by weight, calculated for the weight of flumequine, of polyvinyl pyrrolidone or an amino acid monomer or polymer containing basic group (s) or with 20-100 % by weight, calculated xor the weight ox flumequine, of urea, and optionally with a known pharmacotechnological granulation aid, and the mixture is subjected to wet granulation.
  • flumequine is present as its complex formed with the complexing agent applied, i.e. with polyvinyl pyrrolidone, an amino acid monomer or polymer containing basic grou ⁇ (s) or urea.
  • the complexing agent applied i.e. with polyvinyl pyrrolidone, an amino acid monomer or polymer containing basic grou ⁇ (s) or urea.
  • Amino acid monomers or polymers containing basic grou ⁇ (s), utilized as complexing agents are amino
  • acids which contain over the -NH 2 group characteristic of such compounds at least one further nitrogen-containing basic group, such as one additional amino group, too.
  • these amino acids are lysine and arginine.
  • an amino acid polymer containing basic group(s) refers to oligomsrs and polymers formed from these amino acids by peptide bonds.
  • the mass to be granulated may also contain one or more known pharmacotecnnologieal granulation aid.
  • These granulation aids may be substances for inhibiting adhesion and substances for improving distribution.
  • the substances for inhibiting adhesion are silicon dioxides with high specific surface area (such as Aerosil) and magnesium stcarate.
  • As substances for improving distribution pharmaceutically acceptable water-soluble neutral pcrticulatc solids can be applied, characteristic representatives of which are sugars (such as lactose and glucose) and polysaccharides (such as various starch types).
  • sugars such as lactose and glucose
  • polysaccharides such as various starch types
  • a granulation aid particularly if polyvinyl pyrrolidone or a basic amino acid polymer is applied as complexing agent. If a granulation aid is also present in the mass to be granulated, its amount may be e.g. 1-100% by weight, calculated for the weight of flumequine.
  • Granules are prepared according to the invention by any of the wet granulation methods well known in pharmacotcchnology.
  • Pharmaceutically acceptable inorganic or organic liquids such as water or an alcohol, can be utilised as granulating liquids.
  • the total amount or a part of the complexing agent and/or of the granulation aid is admixed to the mass to be granulated as a solution formed with the granulating liquid.
  • the mass to be granulated may have typically e.g. one of the following compositions:
  • the granules according to the invention may be applied directly for veterinary purposes, e.g. they can be dissolved in the drinking water of animals. If
  • the granules according to the invention can be converted into veterinary compositions, such as powder mixtures, tablets, capsules, injectuble compositions etc., by conventional phermacotechnological opera tions, utilizing conventional veterinary carriers, diluents and/or other auxiliary agents (such as surfactants).
  • veterinary compositions can be applied to advantage e.g. for individual treatment or for the treatment of a smaller population.
  • the invention also relates to such veterinary compositions as well as to their preparation.
  • the veterinary compositionc according to the invention may also comprise adjuvants.
  • Preferred representatives of adjuvants are bactoriolytic enzymes which facilitate flumequine to reach its point of attack, i.e. to reach the infecting microorganism.
  • the known veterinary compositions comprising flumequine as its alkaline salt cannot be combined with such enzymes which arc characteristic representatives of alkali-sensitive substances.
  • adjuvant e.g. lysosimc or an acid addition salt thereof can be applied.
  • the veterinary compositions according to the invention may comprise an adjuvant generally in an amount ox 0.5-10 % by weight, preferably 1-3% by weight, calculated for the weight of the composition.
  • flumequine can not only be converted into a water-soluble form
  • Granules are prepared from the following components
  • the half of polyvinyl pyrrolidine is added to the pre -homogenized mixture of the further components as a 20 % by weight ethanol solution.
  • the granules are prepared by fluidisation technique.
  • the granules prepared according to Example 1 are homogenized in a drum with 129.35 kg of lactose. A powder mixture suitable for veterinary purposes is obtained.
  • Granules are prepared as described in Example 1 from the following components:
  • Example 2 One proceeds as described in Example 1 with the difference that water is used as granulating liquid and the granules are prepared from the following components: flumequine 10.0 kg
  • Example 2 One proceeds as described in Example 1 with the difference that an aqueous gel of potato starch is used as granulating liquid and the granules are prepared from the following components:
  • Group II 5 days' treatment with a composition according to French patent Ho. 2,453,647 comprising flumequine as its sodium salt, at a therapeutic level of 12 mg/kg
  • Group III 5 days treatment with a composition according to Example 2 at a therapeutic level of 10 mg/kg

Abstract

The invention relates to granules comprising a water-soluble complex of flumequine formed with polyvinyl pyrrolidone, an amino acid monomer or polymer containing basic group(s) or urea. These granules are prepared according to the invention by admixing flumequine with one of the above complexing agents and optionally with a granulation aid and subjecting the mixture to wet granulation. The invention also relates to veterinary compositions prepared from the above granules.

Description

GRANULES AND VETERINARY COMPOSITIONS COMPRISING A WATER- SOLUBLE COMPLEX OF FLUMEQUINE
The invention relates to granules comprising a water- soluble complex of flumequine, as .veil as to a process for the pre par it ion of such granules. The invention also relates to veterinary compositions produced from the granules according to the invention.
As known, flumequine (6,7-dihydro-9-fluoro-5-methyl-1-oxo-1H,5H-benzo-quinolysine-2-carboxylic acid) is an effective antimicrobial agent, highly active against various microorganisms, such as Aeromonas, Escherichia coli, Proteus, Klebsiella, Salmonella and Ihiterobacter species
(DOJ HO. 2,264,163).
Flumequine is, however, only spairingly soluble in water, which renders difficult to convert it into pharmaceutical and veterinary compositions and also restricts its therapeutic use. According to French patent No. 2,453,647 these, difficulties are overcome. by converting flumequine into pharmaceutical compositions in admixture with sodium carbonate; thus the resulting compositions comprise flumequine as its water-soluble sodium salt. According to the cited reference a water-soluble powder mixture comprising
3-10.5 % by weight of flumequine can be prepared by admixing flumequine with sodium carbonate and lactose. Over these powders additional pharmaceutical compositions, such as tablets, injectable aqueous suspensions and ointments, are also mentioned in the cited reference; these composi tions are prepared by methods conventionally applied in pharmacotechnology.
We have found that these known compositions do not meet all the requirements of pharmaceutical and veterinary use. The 3θlid and semisolid compositions, such as powder mixtures and ointments, are liable to segregation, which impairs the security of dosing. Considerable disadvantages arise from the alkaline nature of the compositions. This alkalinity renders the compositions les3 stable, and restricts both their fields of use and their compatibility with other active agents. Thus e.g. alkaline compositions are less suitable for injection purposes, may cause repellency when mixed into drinking water, and cannot be combined with proteins, enzymes and other alkali-sensitive substances. Our investigations have shown that these disadvantages cannot be overcome by utilizing other salts of flumequine, either.
How we have found that the disadvantages outlined above can be eliminated completely when flumequine is admixed with polyvinyl pyrrolidine, an amino acid monomer or polymer comprising basic group (s) or urea and optionally with a known pharmacoteehnological granulation aid, and the resulting mixture is granulated in wet state. Under such conditions flumequine forms a complex with the polyvinyl pyrrolidine, amino acid monomer or polymer or urea present. The resulting complex is highly water-soluble and forms a neutral aqueous solution. Owing to their neutrality, these complexes are much more suitable for injection or oral administration than the known alkaline flumequine salts, and can be combined unrestrictedly with alkalisensitive substance s . The granulation technique applied according to the invention ensures, on one hand, the homogeneity of the admixed components, and, on the other hand, provides the flumequine complex as a product easy to handle and particularly suitable for processing into a veterinary composition.
Thus the invention relates to granules comprising a water-soluble complex of flumequine formed with polyvinyl pyrrolidone, an amino acid monomer or polymer containing basic group (s) or urea.
These granules are prepared according to the invention as follows: flumequine is admixed with 5-55 % by weight, calculated for the weight of flumequine, of polyvinyl pyrrolidone or an amino acid monomer or polymer containing basic group (s) or with 20-100 % by weight, calculated xor the weight ox flumequine, of urea, and optionally with a known pharmacotechnological granulation aid, and the mixture is subjected to wet granulation.
In these granules flumequine is present as its complex formed with the complexing agent applied, i.e. with polyvinyl pyrrolidone, an amino acid monomer or polymer containing basic grouρ(s) or urea. These complexes are new compounds, When the mixture to be granulated contains the complexing agent in excess related to the stoichiomctrically required value, this excess serves as a carrier.
Amino acid monomers or polymers containing basic grouρ(s), utilized as complexing agents, are amino
acids which contain over the -NH2 group characteristic of such compounds at least one further nitrogen-containing basic group, such as one additional amino group, too. Examples of these amino acids are lysine and arginine.
The term "an amino acid polymer containing basic group(s)" refers to oligomsrs and polymers formed from these amino acids by peptide bonds.
The mass to be granulated may also contain one or more known pharmacotecnnologieal granulation aid. These granulation aids may be substances for inhibiting adhesion and substances for improving distribution. Examples of the substances for inhibiting adhesion are silicon dioxides with high specific surface area (such as Aerosil) and magnesium stcarate. As substances for improving distribution pharmaceutically acceptable water-soluble neutral pcrticulatc solids can be applied, characteristic representatives of which are sugars (such as lactose and glucose) and polysaccharides (such as various starch types). In the presence of granulation aids the mass to be granulated is more easy to homogenise, granulation can bo performed more simply, and granules with more even particle size are formed. It is preferred to use a granulation aid particularly if polyvinyl pyrrolidone or a basic amino acid polymer is applied as complexing agent. If a granulation aid is also present in the mass to be granulated, its amount may be e.g. 1-100% by weight, calculated for the weight of flumequine.
Granules are prepared according to the invention by any of the wet granulation methods well known in pharmacotcchnology. Pharmaceutically acceptable inorganic or organic liquids, such as water or an alcohol, can be utilised as granulating liquids. According to a preferred method the total amount or a part of the complexing agent and/or of the granulation aid is admixed to the mass to be granulated as a solution formed with the granulating liquid.
The mass to be granulated may have typically e.g. one of the following compositions:
a) 10 - 20 parts by weight of flumequine
0.1 - 1 part by weight of Aerosil
0.5 - 2 parts by weight of polyvinyl pyrrolidone b) 10 - 20 parts by weight of flumequine
0.1 - 1 part by weight of Aerosil
2 - 4 parts by weight of lactose
0.5 - 2 parts by weight of polyvinyl pyrrolidone c) 10 - 20 parts by weight of flumequine
0.5 - 5 parts by weight of lysine
d) 10 - 20 parts by weight oi flumequine
3 - 20 parts by weight of urea
e) 10 - 20 parts by weight of flumequine
0.1 - 2 parts by weight of starch
0.5 - 5 parts by 'weight of polylysine
The granules according to the invention may be applied directly for veterinary purposes, e.g. they can be dissolved in the drinking water of animals. If
desired, however, the granules according to the invention can be converted into veterinary compositions, such as powder mixtures, tablets, capsules, injectuble compositions etc., by conventional phermacotechnological opera tions, utilizing conventional veterinary carriers, diluents and/or other auxiliary agents (such as surfactants). Such veterinary compositions can be applied to advantage e.g. for individual treatment or for the treatment of a smaller population. The invention also relates to such veterinary compositions as well as to their preparation.
The veterinary compositionc according to the invention may also comprise adjuvants. Preferred representatives of adjuvants are bactoriolytic enzymes which facilitate flumequine to reach its point of attack, i.e. to reach the infecting microorganism. The known veterinary compositions comprising flumequine as its alkaline salt cannot be combined with such enzymes which arc characteristic representatives of alkali-sensitive substances. As adjuvant e.g. lysosimc or an acid addition salt thereof can be applied. The veterinary compositions according to the invention may comprise an adjuvant generally in an amount ox 0.5-10 % by weight, preferably 1-3% by weight, calculated for the weight of the composition.
It has been found, unexpectedly, that the granules and veterinary compositions according to the invention, which comprise flumequine as its water-soluble
complex, exert more favourable therapeutical effects
than the respective known compositions which comprise flumequine as its salt administered on the same therapeutic level. Thus according to the invention flumequine can not only be converted into a water-soluble form
which is easy to handle and can be applied to advantage in pharmacotechnological operations, but the biological value of the active agent can be improved, too.
The invention is elucidated in detail by the aid of the following non-limiting Examples.
Example 1
Granules are prepared from the following components
Flumequine 15.15 kg
Aerosil 200 0.50 kg
Polyvinyl pyrrolidone 1.00 kg
Lactose 2.50 kg
The half of polyvinyl pyrrolidine is added to the pre -homogenized mixture of the further components as a 20 % by weight ethanol solution. The granules are prepared by fluidisation technique.
Example 2
The granules prepared according to Example 1 are homogenized in a drum with 129.35 kg of lactose. A powder mixture suitable for veterinary purposes is obtained.
Example 3
Granules are prepared as described in Example 1 from the following components:
Plumequine 10.00 kg
Aerosil 200 0.20 kg
Polyvinyl pyrrolidone 1.00 kg
Lactose 2.00 kg
Example 4
One proceeds as described in Example 1 with the difference that water is used as granulating liquid and the granules are prepared from the following components: flumequine 10.0 kg
Urea 7.0 kg
Example 5
One proceeds as described in Example 1 with the difference that an aqueous gel of potato starch is used as granulating liquid and the granules are prepared from the following components:
Plumequine 10.0 kg
Lysine 2.0 kg
Potato starch 0.3 kg
Example 6
Comparative biological tests were performed on 120 4 weeks old Tetra-3 broiler cocks. The animals were infected artificially with Salmonella typhimurium. When the symptoms of infection became observable the animals were divided into three equal groups, and the individual groups were kept separately in cages of 20 animals/m2. The individual groups were treated as follows:
Group I: untreated control
Group II: 5 days' treatment with a composition according to French patent Ho. 2,453,647 comprising flumequine as its sodium salt, at a therapeutic level of 12 mg/kg
Group III : 5 days treatment with a composition according to Example 2 at a therapeutic level of 10 mg/kg
The results were evaluated at the end of the 5th day. The following results were obtained: Group I Group II Group III
Mortality in 5 clays 25 % 12.5 % 5 %
Diarrhoeal day s related to Group I 5 % 3 %

Claims

What we claim is :
1. Granules comprising a water-soluble complex of flumequine formed with polyviny l pyrrolidone , an amino acid monomer or polymer containing basic group (s ) or urea .
2. Granules as claimed in claim 1, in which the water-soluble complex of flumequine is formed with polyvinyl pyrrolidone.
3. A process for the preparation of granules according to claim 1, in which flumequine is admixed with
5-55 % by weight, calculated for the weight of flumequine, of polyvinyl pyrrolidone or an amino acid monomer or polymer containing basic group(s) or with 20-100 % by weight, calculated for the weight of flumequine, of urea, ana optionally with a known pharmacotechnological granuletion aid, and the mixture is subjected to wet granulation.
4. A process as claimed in claim 3, in which granulation is performed in the presence of 1-100 % by weight, calculated for the weight of flumequine, of a conventional pharmacotechnological granulation aid.
5. A process as claimed in claim 4, in which granulation is performed in the presence of 7-50% by
weight, calculated for the weight of flumequine, of polyvinyl pyrrolidone.
6. A process as claimed in any of claims 3 to 5, in which a silicon dioxide with high specific surface area and/or a sugar is applied as granulation aid.
7. A veterinary composition which comprises granules comprising a water-soluble complex of flumequine formed with polyvinyl pyrrolidone, an amino acid monomer or polymer containing basic group (s) or urea, together with a conventional veterinary diluent or carrier and optionally with an adjuvant.
8. A veterinary composition as claimed in claim 7, which comprises granules comprising a water-soluble complex of flumequine formed with polyvinyl pyrrolidone
9. A veterinary composition as claimed in claim 7 or 3, which comprises lysosime or an acid addition salt thereof as adjuvant in an amount of 0.5-10 % by weight calculated for the weight of the composition.
10. A process for the preparation of a veterinary composition as claimed in claim 7, in which the granules prepared as claimed in claim 3 are converted into a veterinary composition by a known pharmacotechnological operation in combination with a conventional veterinary diluent or carrier and optionally with an adjuvant.
11. A process as claimed in claim 10, in which granules prepared as claimed in claim 5 are applied.
12. A process as claimed in claim 10 or 11, in which lysosime or on acid addition salt thereof is
applied as adjuvant in an amount of 0.5-10 % by weight calculated for the weight of the composition.
PCT/HU1992/000013 1991-03-14 1992-03-13 Granules and veterinary compositions comprising a water-soluble complex of flumequine WO1992016209A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU841/91 1991-03-14
HU84191A HU206975B (en) 1991-03-14 1991-03-14 Process for producing granulation and veterinary composition comprising water-soluble flumequine complex

Publications (1)

Publication Number Publication Date
WO1992016209A1 true WO1992016209A1 (en) 1992-10-01

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HU (1) HU206975B (en)
WO (1) WO1992016209A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997009036A2 (en) * 1995-09-01 1997-03-13 Euro-Celtique S.A. Improved pharmaceutical ion exchange resin composition

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2049420A (en) * 1979-04-10 1980-12-31 Riker Laboratories Inc Veterinary medicament based on benxoquinolizine carboxylic acids and their derivatives
EP0100168A2 (en) * 1982-07-06 1984-02-08 Alan George Rogerson Processes for preparing tablets by a modified 'wet-granulation' technique
WO1987003509A1 (en) * 1985-12-10 1987-06-18 Cerwen Erik Audunn Method for the assembly of polar-nonpolar-polar proteolipid membranes
EP0261426A1 (en) * 1986-08-28 1988-03-30 The Du Pont Merck Pharmaceutical Company Freeze-dried pharmaceutical compositions of phenylquinoline carboxylic acids
US4900775A (en) * 1988-02-29 1990-02-13 Gaf Chemicals Corporation Solubilization of complexes of water-insoluble organic compounds by aqueous solutions of polyvinylpyrrolidone

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2049420A (en) * 1979-04-10 1980-12-31 Riker Laboratories Inc Veterinary medicament based on benxoquinolizine carboxylic acids and their derivatives
EP0100168A2 (en) * 1982-07-06 1984-02-08 Alan George Rogerson Processes for preparing tablets by a modified 'wet-granulation' technique
WO1987003509A1 (en) * 1985-12-10 1987-06-18 Cerwen Erik Audunn Method for the assembly of polar-nonpolar-polar proteolipid membranes
EP0261426A1 (en) * 1986-08-28 1988-03-30 The Du Pont Merck Pharmaceutical Company Freeze-dried pharmaceutical compositions of phenylquinoline carboxylic acids
US4900775A (en) * 1988-02-29 1990-02-13 Gaf Chemicals Corporation Solubilization of complexes of water-insoluble organic compounds by aqueous solutions of polyvinylpyrrolidone

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PATENT ABSTRACTS OF JAPAN, unexamined applications, Field C, Volume 4, Number 190, 26 December 1980 (26.12.80), The Patent Office Japanese Government, page 90 C 37; & JP,A,55 129 220 (YAMANOUCHI SEIYAKU K.K.). *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997009036A2 (en) * 1995-09-01 1997-03-13 Euro-Celtique S.A. Improved pharmaceutical ion exchange resin composition
WO1997009036A3 (en) * 1995-09-01 1997-04-24 Euro Celtique Sa Improved pharmaceutical ion exchange resin composition
US6077532A (en) * 1995-09-01 2000-06-20 Euro-Celtique, S.A. Pharmaceutical ion exchange resin composition

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HU206975B (en) 1993-03-01
HU910841D0 (en) 1991-09-30
EP0575439A1 (en) 1993-12-29

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