GB2049416A

GB2049416A - Pharmaceutical composition

Info

Publication number: GB2049416A
Application number: GB7918187A
Authority: GB
Original assignee: Laroche Navarron SA
Current assignee: Laroche Navarron SA
Priority date: 1979-05-24
Filing date: 1979-05-24
Publication date: 1980-12-31
Also published as: FR2457102A1; FR2457102B1; GB2049416B

Abstract

Chlamydiae-induced diseases such as trachoma and genital infections are treated by a composition containing a sulfa-drug and a titrated extract of Centella Asiatica (ETCA), (contains asiaticoside, asiatic acid and madecassic acid). The sulfa drug may be sulphefurazole, sulphamethoxypyridazine, sulphadimethoxine, sulphamono- methoxine or sulphadoxine.

Description

SPECIFICATION Pharmaceutical composition This invention relates to a new therapeutic composition typically useful for the treatment of Chlamydiaeinduced infections, and particularly of infections induced by Chlamydiae trachomatis.

The infections induced by Chlamydiae trachomatis comprise essentially infections of ocular type (trachoma) and infections of genital type, such as some sexually transmissible diseases (typically non-gonococcal urethritis) (vide: J. Schachter, the New England Journal of Medicine, Vol. 298, 8, 428-435).

Trachoma is an eye disease which affects 450 million subjects in the World. The treatment which is the more frequently used at present is based on the administration of sulfa drugs, typically of long-acting sulfa-drugs.

Applicant has found that it was possible to improve very markedly the treatment of trachoma and, more generally, of Chlamydiae-induced infections, by combining sulfa-drugs, and particularly long-acting sulfa-drugs, with Titrated Extract of Centella Asiatica (referred to hereinafter as ETCA).

Thus, this invention relates to a composition typically useful for the treatment of Chlamydiae-induced infections comprising a combination of a sulfa-drug, typically of a long-acting sulfa-drug, and of ETCA.

ETCA is a combination of three active ingredients: asiaticocide (comprising 60 wt% of the combination) and two genines (comprising together 40 wt% of the combination), i.e., asiatic acid and madecassic acid. All three active ingredients are extracted from Centella Asiatica by hydroalcoholic maceration.

The sulfa-drug used is typically a long-acting sulfa-drug, such as sulfafurazol, sulfamethoxypyridazine, sulfadimethoxine, sulfamonomethoxine and sulfadoxine.

ETCA and the sulfa-drug are preferably used in an amount of 1 part by weight ETCA per 10-100 parts by weight sulfa-drug.

The composition of this invention may be administered orally (as tablets, capsules, suspension, syrups), topically (as collyria, dermal solutions), or parenterally (as injectable ampoules).

The composition is administrable to humans typically at a dosage of 0.5 - 5 mg ETCA and a dosage of sulfa-drug which represents from 10 to 100 times the amount of ETCA per kg and per day by the oral route.

Examples of therapeutic compositions are given below: Example 1 - Capsule ETCA 30 mg Sulfafurazol < 500 mg Excipient, sufficient to make one capsule (starch, talc, magnesium stearate) Example 2 - Capsule ETCA 30g Sulfamethoxypyridazine 250 mg Excipient, sufficient to make 1 capsule (starch, talc, magnesium stearate) Example 3 - Tablet ETCA 15mg Sulfafurazol 500 mg Excipient, sufficient to make 1 tablet (starch, talc, magnesium stearate, gelatin) Example 4 - Tablet ETCA 30 mg Sulfadimethoxine 500 mg Excipient, sufficient to make 1 tablet (starch, talc, magnesium stearate, gelatin) Example 5- Collyrium ETCA ig Sulfafurazol 15g Excipient, sufficient to make 100 cc (benzyl alcohol, phenylmercury nitrate, disodium citrate, polyvidone, polyoxyethylene glycol, Tween 80, purified water) Example 6- Injectable ampoule ETCA 0.02 g Sulfafurazol 2g Excipient, sufficient for a 5 cc ampoule Example 7- Syrup ETCA 0.5 g Sulfisomidine lOg Excipient, sufficient to make 100 ml (sucrose, methylcellulose, Tween 20, citric acid, purified water) The results of an in vitro investigation carried out on the strain responsible fortrachoma are given below.

The tests were effected on cultures of HELA human cells inoculated with Chlamydiae trachomatis responsible for the trachoma.

A portion of the cultures was kept as reference.

To the other portion were added, 24 hours after infestation: - either 75 mcg/ml ETCA - or 500 mcg/ml sulfafurazol - or 500 mcg/ml sulfafurazol + 75 mcg ECTA.

A count was made of the number of cellular inclusions induced by Chlamydiae trachomatis.

The results obtained are set forth in the following Table (As percentage of infected cells).

Days Infected Infected Infected Infected cells reference cells cells 75y/ml ETCA cells 75 y/ml 500 y/ml 500y/mlsulfa ETCA sulfafurazol furazol 1 11.4 4.8 9.9 1.1 2 22.6 12 3.5 0.8 3 61 28 2.5 0.8 4 100 8.5 1 0.05 5 Dead lysed cells 9.2 0.8 0.6 6 Dead lysed 52.5 1 0.4 cells It is found that while ETCAperse has a substantial effect on the number of infected cells, the effect obtained with the ETCA + sulfafurazol combination is greatly superior, and also superior to that obtained with sulfafurazol alone.

Comparative clinical tests effected, on the one hand, with ETCA, sulfisomidine and the ETCA + sulfisomidine combination and, on the other hand, with ETCA, sulfamonomethoxine and ETCA + sulfamonomethoxine on patients suffering from trachoma confirmed the marked superiority of the treatment with the ETCA + sulfa-drug combination, over treatment with a sulfa-drug alone, and also a substantial superiority of this treatment over treatment with ETCA alone.

In its broadest sense, the invention is to be understood to include pharmaceutical compositions comprising (i) a sulfa drug and (ii) asiaticocide, asiatic acid and madecassic acid. Component (ii) will conveniently comprise 60% by weight asiaticocide and 40% by weight asiatic acid and madecassic acid and in general will simply be ETCA as identified herein before.

The invention includes a system comprising components (i) and (ii), typically in a package or the like, separately and in a form conveniently mixable to form the composition defined above. For example, the system may comprise a container of component (i) and either a container of component (ii), such as a container of ETCA, or two or more containers each containing one or two of the materials which make up component (ii) and collectively containing all the materials required for making up component (ii).

Claims

1. Composition comprising a combination of a sulfa-drug and Titrated Extract of Centella Asiatica.

2. Composition for the treatment of Chlamydiae-induced infections comprising a combination of a sulfa-drug and Titrated Extract of Centella Asiatica.

3. A composition for the treatment of Chlamydiae-induced infections, substantially as hereinbefore described in any one of the foregoing specific Examples.