PHARMACEUTICAL COMPOSITIONS HAVING TOPICAL USE COMPRISING TICLOPIDINE

Abstract: Pharmaceutical compositions having topical use, particularly in form of creams, containing 5-(2-chloro­ benzyl)-4,5,6,7-tetrahydro-thieno (3.2-c)pyridine (ticlo­ pidine) as active principle are described. They have a therapeutical activity in limbs ischemias, blood vessels alterations, hematomas, superficial traumas and the like.

Description: The present invention relates to pharmaceutical compositions for topical use containing 5-(2-chlorobenzyl)-4,5,6,7-tetrahydro-thieno(3.2-c)-pyridine, of formula I: Compound (I), internationally known as ticlopidine, is used by systemic route as a drug having platelet anti-aggregating anti-thrombotic activity. Now it has been found that compositions for topical use containing ticlopidine, like ointments, lotions andin particular - creams, have a great therapeutical activity in treating limbs ischemias; vessels alterations (thrombophlebitis and phlebothrombosis, post-phlebitis syndromes, varixes, stasis edemas); hematomas, superficial traumas and swellings. Ticlopidine therapeutical activity by topical route is surprising because in literature this kind of activity is unknown. Furthermore it's known that many drugs which are active by systemic route are inactive or practically inactive by topical route. On the other hand topical administration has - where it is possible ot use it - clear advantages, for instance the use of less quantity of active principle and, particularly, the possibility to avoid that notable concentrations of the active principle enter blood circulation. The compositions according to the invention contain ticlopidine (as hydrochloride) from 1 to 10% and preferably from 2 to 6% in weight, together with excipients and preservatives already known in pharmaceutical technique. Creams with 3 - 5% of active principle (in form of hydrochloride) as shown hereinbelow, are an example. EXAMPLE 1 EXAMPLE 2 EXAMPLE 3 EXAMPLE 4 EXAMPLE 5 EXAMPLE 6 The pharmaceutical compositions of the invention allow a quick and remarkable attenuation of the symptoms, that then completely disappear, in 80-90% of the cases in which they have been experimented. These cases included thrombophlebitis and phlebothrombosis, acentrated limbs ischemias; and also hematomas caused by contusions and vessel fragility, swellings of various kinds and varixes. Tolerability controls, carried out using the 5% active principle creams, (see Example 4) preceeded the above mentioned experiments. The following tables summarize the results of the "acute study" (primary irritation and light-sensitive capacity test in guinea-pigs) As it is stated by Table 1 and 2, the cream turns out to be included among the classifications where it is not considered irritant, while Table 3 shows the complete absence of light-sensitive phenomena. Furthermore, the local chronic tolerability in rabbits was valued. The above mentioned cream was applied daily and for one month in a shaven area ( 50 cm²) of whitish rabbits right side. Weekly shavings occurred, while the excipients were tested in the same way on the left side. Tolerability was very good for all the twelve animals; as regards the controls, no variations in weight increase, in hematological and hematochemical pattern, at the macroscopic, weighting and histological exam of the organs, and also of the hemodynamic and breathing parameters were shown. See, for instance, Table 4-5-6.

Claims: Pharmaceutical compositions adapted only for topical use, containing as active principle 5-(2-chlorobenzyl)-4,5,6,7-tetrahydro-thieno (3,2-c)pyridine (ticlopidine) of formula I: Pharmaceutical compositions according to claim 1, for the treatment of limbs ischemias; vessels alteration (thrombophlebitis, phlebothrombosis, post-phlebitis syndromes, varixes, stasis edema); hematomas, superficial traumas and swellings. Pharmaceutical compositions, according to claims 1 and 2, containing from 1 to 10% in weight of ticlopidine. Pharmaceutical compositions, according to claim 3, containing from 2 to 6% in weight of ticlopidine. Pharmaceutical compositions, according to claim 4, in form of creams containing 3-5% in weight of ticlopidine.

Inventors: STEFANELLI, EMILIO
Applicants: ISTITUTO BIOCHIMICO NAZIONALE SAVIO S.R.L.
Application year: 1989
Main classification: A61K31
IPC codes: A61K47, A61K31, A61K9