Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-06-17
2000-02-22
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514456, 514460, 514617, 514622, 548252, 548253, 548254, 549401, 549404, 549407, 549414, 564161, A61K 3135, A61K 3141, C07D25704, C07D40504
Patent
active
060280921
DESCRIPTION:
BRIEF SUMMARY
This invention relates to novel formulations of compounds having pharmacological activity, to compositions containing them and to their use in the treatment of certain disorders.
N-[4-Oxo-2-(1H-tetrazol-5-yl)-4H-1-benzopyran-8-yl]-4-(4-phenylbutoxy)benza mide, that is to say, the compound of the following structure: ##STR1## is known in the art as a compound which is useful as a leukotriene antagonist. In particular, the compound is disclosed in EPA 173 516 as being useful for the treatment of asthma. However this type of compound is relatively insoluble in many solvents commonly used in pharmaceutical formulations. This is clearly a disadvantage, since solubility can affect the bioavailability of any drug. There is therefore a need for novel formulations which overcome the above problems. It has been found that specific salts of the above compound are surprisingly soluble in certain organic solvents.
The present invention therefore provides, in a first aspect, a compound of formula (I): ##STR2## in the form of a salt characterised in that the salt is the sodium, potassium, ammonium calcium, Tris, triethanolamine, ethylenediamine or N-methyl glucamine salt.
Preferred inorganic salts include the sodium and ammonium salts.
These salts of the compound of formula (I) can be used in therapy, particularly for the treatment of asthma. Thus the invention also provides a salt as described herein, for use as a therapeutic substance, in particular for the treatment or prophylaxis of asthma.
Salts of the invention can be formulated in standard pharmaceutical compositions. The present invention therefore provides a pharmaceutical composition, which comprises a salt as described herein and a pharmaceutically acceptable carrier or mixture of carriers.
The salts of the invention show enhanced solubility in aqueous media when compared to the free acid. Therefore the carrier can be an aqueous based carrier. Advantageously, the salts of the invention can be formulated with one or more organic solvents, particularly solvents containing one or more hydroxy groups such as alcohol and glycol solvents. Preferred solvents include polyethylene glycols such as PEG 200 and PEG 400 as well as lower alcohols, in particular ethanol and n-propanol. Mixtures of two or more solvents can be used, including mixtures of alcohols or glycols in water. Particularly preferred compositions which exhibit excellent bioavailability are those containing the ammonium salt in PEG 400.
In a particular embodiment of the invention the salts of the invention can be formulated with polyethylene glycols at elevated temperature and the mixture then cooled and used to fill gelatin capsules.
Alternatively salts may be prepared in situ at the formulation stage from the parent compound of formula I and appropriate quantities of a neutralising base such as ammonium carbonate or sodium carbonate.
The invention further provides a method of treatment or prophylaxis of asthma, in mammals including humans, which comprises administering to the sufferer a therapeutically effective amount of a salt as described herein.
In another aspect, the invention provides the use of a salt as described herein in the manufacture of a medicament for the treatment or prophylaxis of the above disorders.
A pharmaceutical composition of the invention, which may be prepared by admixture, suitably at ambient temperature and atmospheric pressure, is usually adapted for oral, parenteral or rectal administration and, as such, may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable or infusable solutions or suspensions or suppositories. Orally administrable compositions are generally preferred, particularly capsules.
Compositions for oral administration may be in unit dose form, and may contain conventional excipients known in the pharmaceutical art.
Oral liquid preparations may be in the form of, for example, aqueous or oily suspension, solutions, emulsions, syrups or elixirs, or may be in the form of a dry product for r
REFERENCES:
Hackh's Chemistry Dictionary, Fourth Ed., Julius Grant, Ed., p. 249, 1969.
The Merck Index, Tenth Edition, Martha Windholz, Ed., pp. 207, 219, and 7439, 1983.
Aldrich, Catalog Handbook of Fine Chemicals, p. 1702, 1998-99.
Banton Christopher John
Buxton Phillip Christopher
Kanagy James M
Kinzig Charles M.
Oswecki Jane C.
Richter Johann
SmithKline Beecham p.l.c
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