Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1991-11-04
1993-11-30
Waddell, Frederick E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
514858, A61K 3156
Patent
active
052665666
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to the anti-fungal use of certain steroids.
2. Description of the Prior Art
UK Patent 2161380 B (National Research Development Corporation) describes the anti-fungal, especially anti-Candida use of, bile acids and derivatives thereof, collectively having the formula ##STR2## wherein each of X, Y and Z independently represents a hydrogen atom or a hydroxyl group or a derivative thereof which is a conjugate formed between the carboxyl group and the NH.sub.2 group of an amino acid, and their pharmaceutically acceptable salts.
It has been a problem to find alternative anti-fungal compounds having improved therapeutic action against various fungi invasive to the human body.
SUMMARY OF THE INVENTION
It has now been found that compounds of the general formula (2): ##STR3## wherein X is a hydrogen atom or a hydroxyl group, Y is a hydrogen atom or a hydroxyl group and R is an alkyl group of 1 to 4 carbon atoms, have useful anti-fungal activity. Against some fungi, at least, activity appears to be better than is obtainable from the bile salts of the prior patent. Such fungi include Candida species and the fungi implicated in athlete's foot and ringworm (Trichophyton mentagrophytes and Microsporum audonii). The compounds of the invention are of particular interest for topical application.
The compounds of general formula (2) are mostly known compounds. This invention comprises the specific medical use thereof as anti-fungal agents, said uses to be claimed in the conventional manner appropriate to national patent law. Thus, in particular, the invention, in EPC countries, includes the use of a compound of formula (2) for the manufacture of a medicament for the therapeutic application of treating fungal infections, especially by topical application, while for US purposes it includes a method of treatment of a fungal infection in a human patent, which comprises administering to the patient, preferably topically, a therapeutically effective amount of a compound of formula (2).
Although, as indicated, the anti-fungal use of deoxycholic acid (including its non-toxic salts) is the subject of the said prior patent, the only anti-fungal use specifically described is against Candida. It has now become apparent, from further testing, that deoxycholic acid has a poorer action against Candida (see Table 1 below) compared with the other bile acids of formula (1). On the other hand, it is unexpectedly very highly effective against the Microsporum audonii organism implicated in ringworm. According to a further feature of the invention, therefore, there is provided the use of deoxycholic acid and its non-toxic salts as a topical anti-fungal for treatment of infections of Microsporum audonii or for which M. audonii is a suspected causative agent, especially ringworm. As for the compounds of formula (2) such use is to be claimed in the manner appropriate to national patent law, especially as indicated above. Whereas in the prior patent the sites of topical application specifically mentioned were the vagina, the throat and other cavities, the present application contemplates in relation to deoxycholic acid primarily uses externally of the body cavities and to the ordinary skin.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Investigations into the effectiveness of various bile acid derivatives has shown that the compounds of the invention have a greater activity against at least one of the three selected fungal strains than salts of the corresponding bile acids of formula (1). These tests are reported below. They indicate in particular that the following methyl esters of formula (2) are particularly effective against the following organisms:
______________________________________ X = H, Y = OH vs Candida albicans
("deoxycholic")
X = OH, Y = OH
vs Trichophyton mentagrophytes
("cholic") and Microsporum audonii
______________________________________
reasonable to suppose that the ethyl, n-propyl, isopropyl, other n-butyl,
isobutyl and t-butyl esters
REFERENCES:
Berger Medicinal Chemistry, p. 75, 1985.
Marples Brian A.
Stretton Reginald J.
British Technology Group Limited
Hook Gregory
Waddell Frederick E.
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