TRANSDERMAL THERAPEUTICAL SYSTEM FOR SILATRAN COMPOUNDS

SYSTEME THERAPEUTIQUE TRANSDERMIQUE POUR L'ADMINISTRATION DE COMPOSES DE SILATRAN

English Abstract

A preparation containing a silatran is, in the form of a transdermal
therapeutical system, suitable for the prevention and/or treatment of hair or
wool loss.

French Abstract

L'invention concerne une préparation contenant un silatran, laquelle se présente sous la forme d'un système thérapeutique transdermique et convient à la prophylaxie et/ou au traitement de la chute de la laine et des cheveux.

Claims

CLAIMS
1. A preparation for the prophylaxis and/or treatment of wool or
hair loss comprising the active substance silatrane of the formula
<IMG>
wherein
R = H or CH3,
Z = a double-bond group comprising 1 to 3 C-atoms and optionally
substituted by chlorine,
and
X = H, low alkyl, aryl, halogen, CF3, CN, NH2, SH, CNS, R1M,
(R2O)2P(O), R3C(O)M with R1 = alkyl, straight-chain or branched,
with 1 to 4 C-atoms, aryl, aralkyl, alkaryl,
M = O, S, R2 = methyl, ethyl, R3 = alkyl with 1 to 4 C-atoms,
fluoroalkyl with 1 to 4 C-atoms, or aryl,
characterized in that
it is present in the form a transdermal therapeutic system.
2. The preparation according to claim 1 characterized in that it is
present as a patch.
3. The preparation according to claim 2 characterized in that the
patch comprises an impermeable backing layer, an active substance
reservoir connected therewith, a membrane controlling the

release of the active substance in the absence of other control
mechanisms, a pressure-sensitive adhesive device to fix the patch
to the skin, and, if necessary, a protective layer removable prior to
application.
4. The preparation according to one or several of claims 1 to 3
characterized in that it comprises 0.1 to 50%-wt., preferably 3 to
25%-wt., and most preferably 5 to 15%-wt. of active substance.
5. The preparation according to one or several of claims 1 to 4
characterized in that it comprises 1-(chloromethyl)-silatrane as
active substance.
6. The preparation according to one or several of claims 1 to 4
characterized in that it comprises 1-(ethoxy)-silatrane as active
substance.

Description

. CA 02232026 1998-03-13
Preparation for the prophylaxis and/or treatment of
wool and hair loss
SPECIFICATION
The present invention relates to a transdermal therapeutic system
(TTS) for the prophylaxis and/or treatment of wool and hair loss.
The effectiveness of substituted silatranes as a wool and hair re-
storer is known from German patent specification 26 15 654.
The good tolerance of the compound employed is particularly em-
phasized. According to this document, administration is effected
either as an addition to the food, which is particularly suitable for
animals, or by rubbing ointments or suspensions. If applied several
times a week, the duration of treatment is in the range of some
months. However, the state of the art is unsatisfactory because of
the heavy demands made on patients' compliance; moreover, the
amount of active substance administerèd is difficult to control
because of the known deficiencies in connection with an ointment
or suspension application.
Proceeding from this state of the art, it is the object of the present
invention to provide a new application form overcoming the men-
tioned disadvantages in the use of substituted silatranes for the
prophylaxis and/or treatment of wool and hair loss.

. CA 02232026 1998-03-13
.
This object is achieved by the fact that the preparation comprising
substituted silatranes of the formula
/\N/\
R--~/1 \0
z
O
X
is made in the form of a transdermal therapeutic system.
With the following meanings:
R = H or CH3,
Z = a double-bond group comprising 1 to 3 C-atoms and option-
ally substituted by chlorine,
and
X = H, low alkyl, aryl, halogen, CF3, CN, NH2, SH, CNS, RlM,
(R20)2P(O), R3C(O)M with
R~ = alkyl, straight-chain or branched, with 1 to 4 C-atoms, aryl,
aralkyl, alkaryl, M = O, S
R2 = methyl, ethyl, R3 = alkyl with 1 to 4 C-atoms, fluoroalkyl
with 1 to 4 C-atoms, or aryl.
Therapeutic systems (TTS) comprise one or several active sub-
stances which are continuously released at a predetermined rate
over a definite period of time to a definite site of application (Heil-
mann, Therapeutische Systeme - Konzept und Realisation pro-
grammierter Arzneiverabreichung, 4th edition, Ferdinand Enke
Verlag Stuttgart, 1 984, p . 26) .

CA 02232026 1998-03-13
Among these therapeutic systems, patches having a transdermal
action are preferred according to the present invention, one reason
is that silatranes are suitable for skin penetration because of their
globular molecular shape.
TTSs in patch form are known to the skilled artisan. In general,
they comprise an impermeable backing layer, an active substance
reservoir connected therewith, a membrane controlling the release
of the active substance in the absence of other control mecha-
nisms, a pressure-sensitive adhesive devicé to fix the patch to the
skin, and, if necessary, a protective layer removable prior to appli-
cation. If the active substance reservoir is self-adhesive by itself,
the TTS may be manufactured by homogeneously mixing the ac-
tive substance, auxiliary agents, and pressure-sensitive adhesive
polymers in a suitable solvent, spreading the solution on the
backing layer, removing the solvent, and applying a protective
layer. It is also possible to reverse the succession of layers.
On principle the reservoir may also be manufactured from the
melt.
A synthesis of the active substances to be used according to the
present invention is described in German patent specification 25
22 982. 1-(chloromethyl) silatrane and 1-(ethoxy)-silatrane are
particularly preferred because of their good tolerance.
The concentration of at least one active substance from the sila-
trane group within the reservoir amounts to about 0.1 to 50%-wt.,
preferably to about 3 to 25%-wt., and most preferably to 5 to
1 5%-wt. The dose per patch may then be adjusted by the selec-
tion of the layer thickness and the dimension of the reservoir;
among other things, it depends on the age and the skin surface of
the patient, as well as on the kind and degree of hair loss.

CA 02232026 1998-03-13
When used for animals, similar considerations are applicable.
The silatrane-containing TTS provides an application form for an
agent that can be used over a longer period for the prophylaxis
and treatment of wool and hair loss, which makes the duration of
effect of one single administration last over several weeks and
months and ensures a desired dosage of the active substance. -
Moreover, the systemic action of silatranes does-not necessarily Z
require a topical application.