Sélection de la langue

Search

Sommaire du brevet 2114537 

Énoncé de désistement de responsabilité concernant l'information provenant de tiers

Une partie des informations de ce site Web a été fournie par des sources externes. Le gouvernement du Canada n'assume aucune responsabilité concernant la précision, l'actualité ou la fiabilité des informations fournies par les sources externes. Les utilisateurs qui désirent employer cette information devraient consulter directement la source des informations. Le contenu fourni par les sources externes n'est pas assujetti aux exigences sur les langues officielles, la protection des renseignements personnels et l'accessibilité.

Disponibilité de l'Abrégé et des Revendications

L'apparition de différences dans le texte et l'image des Revendications et de l'Abrégé dépend du moment auquel le document est publié. Les textes des Revendications et de l'Abrégé sont affichés :

  • lorsque la demande peut être examinée par le public;
  • lorsque le brevet est émis (délivrance).
(12) Demande de brevet: (11) CA 2114537
(54) Titre français: SYSTEMES THERAPEUTIQUES TRANSDERMIQUES
(54) Titre anglais: TRANSDERMAL THERAPEUTIC SYSTEMS
Statut: Morte
Données bibliographiques
(51) Classification internationale des brevets (CIB):
  • A61K 9/70 (2006.01)
  • A61K 47/10 (2017.01)
  • A61K 47/14 (2017.01)
(72) Inventeurs :
  • RIEDL, JUTTA (Allemagne)
  • LIPP, RALPH (Allemagne)
  • HARTISCH, MATTHIAS (Allemagne)
(73) Titulaires :
  • SCHERING AKTIENGESELLSCHAFT (Non disponible)
(71) Demandeurs :
(74) Agent: MARKS & CLERK
(74) Co-agent:
(45) Délivré:
(86) Date de dépôt PCT: 1992-07-07
(87) Mise à la disponibilité du public: 1993-02-18
Requête d'examen: 1999-05-26
Licence disponible: S.O.
(25) Langue des documents déposés: Anglais

Traité de coopération en matière de brevets (PCT): Oui
(86) Numéro de la demande PCT: PCT/EP1992/001515
(87) Numéro de publication internationale PCT: WO1993/002669
(85) Entrée nationale: 1994-01-28

(30) Données de priorité de la demande:
Numéro de la demande Pays / territoire Date
P 41 25 611.5 Allemagne 1991-07-30
P 42 10 165.4 Allemagne 1992-03-25

Abrégés

Abrégé anglais



ABSTRACT

Described are transdermal therapuetic systems characterized
in that they contain, in an adhesive matrix containing an active
substance, a polar penetration enhancer and a non-polar penetration
enhancer which is insoluble in the polar penetration enhancer.

Revendications

Note : Les revendications sont présentées dans la langue officielle dans laquelle elles ont été soumises.



THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:


1. Transdermal therapeutic systems, wherein they contain a
polar penetration enhancer in an adhesive matrix containing an
active ingredient and a nonpolar penetration enhancer insoluble
in the polar enhancer.
2. Transdermal therapeutic systems according to claim 1,
wherein they contain a multivalent alcohol or urea as polar
penetration enhancer.
3. Transdermal therapeutic systems according to claim 2,
wherein they contain 1,2-propanediol, glycerol, sorbitol,
mannitol or dulcitol as multivalent alcohol.
4. Transdermal therapeutic systems according to claims 1 to
3, wherein they contain a hydrocarbon, an alcohol, a fatty acid
or a fatty acid ester with at least 8 carbon atoms each as
nonpolar penetration enhancer.
5. Transdermal therapeutic systems according to claim 4,
wherein they contain isopropyl myristate as fatty acid ester.
6. Transdermal therapeutic systems according to claims 1 to
5, wherein they consist of a top coating impermeable to the
penetration enhancer and optionally also to water, an adhesive
matrix containing an active ingredient adhering to the top
coating, which contains polar and nonpolar penetration enhancers,
and a removable protective layer.
7. Process for the production of transdermal therapeutic
systems according to claim 6, wherein a solution of adhesive is
mixed in a low-boiling solvent with the active ingredient or
active ingredient mixture, the polar and the nonpolar penetration

14

enhancer, the mixture is applied in sheets to a top coating
impermeable to the penetration enhancer and optionally also to
water, the volatile solvent is removed by heating and the
obtained product is covered with a removable protective layer.

Description

Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.


~ 1 211~-~37 ~ ~:

Tra~sdermal Therapeutic ~ystems
The invention relates to transdermal therapeutic systems,
Which are characterized in that they contain a polar penetration
enhancer in an adhesive matrix containing an active ingredient
and a nonpolar penetration enhancer insoluble in the polar
enhancer.
As is known, transdermal therapeutic systems (TTS) are
patche~ containing an active ingredient built up in multiple
layers, which are attached to the skin and which continuously
deliver their active ingredient percutaneously over a longer
period. To reach a therapeutically sufficient penetration rate
of the active ingredient through the skin, it is necessary in
most case~ to provide the transdermal therapeutic systems with
penetration enhancers in addition to the active ingredient.
Transdermal therapeutic systems, which contain a combination
of a polar penetration enhancer and a nonpolar penetration
enhancer, are previously known. ;
But according to the known prior art, the combination
¢apability of the different penetration enhancers required that
they either can be mixed with one another or that they are
processed separately (for example, by layers in different
matrices). (W0-A 90/~4397; EP-A 0305026 and EP-A 0272987).
It has now been found that it is surprisingly possible to
produce transdermal therapeutic systems, which contain a polar
penetration enhancer in an adhesive matrix containing an active
ingredient and a nonpolar penetration enhancer insoluble in the



21~ j3~ :
polar enhancer, without a separation of the components resulting
during the production process.
The thus produced transdermal therapeutic systems according
to the invention have several advantages relative to comparable
systems, which in a matrix contain either only one polar
penetration enhancer or only one nonpolar penetration enhancer:
l. The use of combined penetration enhancers often produces
an unexpectedly great increase of the penetration rate of the
active ingredient.
2. The use of the special combination often results in that
the upper load limits of the individual penetration enhancers can
be exceeded.
3. Poor adhesion of the system to the skin, as it is
observed in transdermal systems which are loaded with a polar
penetration enhancer to the upper load limit, is not observed in
the systems according to the invention.
4. Patch residues, as they are often observed after the
administration of systems that contain nonpolar penetration
enhancers, do not occur.
Overall, the adhesive properties of the transdermal systems
are improved by the combination according to the invention and
their wearing comfort increases by buffering of the moisture
during the wearing.
As the adhesive forming the matrix, the system according to
the invention preferably contains a commercially available
adhesive (Pharmaceutical Technology, 1989, pp. 126-138). Such
adhesives are, for example, polyacrylate adhesives of the


~ 3 ~1t~ 7



Durotak~R) type (National Starch Company), Sichello~R) type
(Sichelwerke [Sickle Factory]3 or Gelva~R) type (Monsanto
Company), synthetic rubber adhesive of Adhesin~R) type (Henkel KG)
or silicone adhesive of X7 type (Dow Corning Corp.)
As polar penetration enhancers, the transdermal systems
according to the invention contain urea or a multivalent alcohol
with preferably 2 to 6 carbon atoms. Such polyols are, for
example, 1,2-ethanediol, 1,3-propanediol, glycerol, sorbitol,
mannitol, dulcitol or especially 1,2-propanediol. In the
finished matrix, the concentration of polar penetration enhancer
is preferably 5 to 25% by weight relative to the total weight of
the matrix.
As nonpolar penetration enhancers, the transdermal system
according to the invention preferably contains a fatty acid ester
with at least 8 carbon atoms.
Fatty acid esters, which are suitable for the process
according to the invention are, for example, those of lauric
acid, myristic acid, palmitic acid, isopalmitic acid, stearic
acid and isostearic acid, CUch as, for example, methyl ester,
ethyl ester, propyl ester, isopropyl ester, butyl ester, sec-
butyl ester, isobutyl ester, tert-butyl ester or glycerol ester.
Such pharmaceutically common fatty acid esters are, for
example, methyl myristate, ethyl myristate, propyl myristate,
methyl laurate, ethyl laurate, propyl laurate, isopropyl laurate,
methyl oleate, ethyl oleate, propyl oleate, isopropyl oleate and
isopropyl palmitate and especially isopropyl myristate.
Certainly, high-boiling liquid hydrocarbons with at least ~ ;

4 ~ 37 ~ ~

carbon atoms and mixtures of these hydrocarbons, such as liquid
paraffin or terpenoid hydrocarbons, such as ~-pinene, d-limonene,
3-carene, myrcene, camphene, bisabolene or squalene, alcohols
with at least 8 carbon atoms, such as, for example, alkanols,
myristyl alcohol or stearyl alcohol or sterines, such as -
cholesterol and also fatty acids with at least 8 carbon atoms,
such as stearic acid, palmitic acid, oleic acid, should also be
suita~le for the production of the transdermal systems according
to the invention. There are not yet any attempts that relate to ;~
this.
~ he nonpolar penetration enhancer is preferably metered so
that its concentration in the ~inished matrix is 1 to 15% by
weight relative to the latter.
Active ingredients which are suitable for the production of
the transdermal systems according to the invention are preferably
those that are poorly soluble in water or insoluble. Suitable,
for example, are steroid hormones, such as:
Progestationally active steroid hormones, such as, for
example, 13-ethyl-17~-hydroxy-18,19-dinor-17a-pregn-4-en-20yl-3-
one (clevonorgestrel), 13-ethyl-17~-hydroxy-18,19-dinor-17a-

pregna-4~15-dien-20yn-3-one (=gestodene) or 13-ethyl-17~-hydroxy- -
11-methylene-18,19-dinor-17~-pregn-4-en-20yn (=desorgestrel),
estrogenically active steroid hormones, 3-hydroxy-1,3,5-(10)-
estrat~ien-17-one (=estrone), 1,3,5(10)-estratriene-3,17~-diol
(=estradiol) or 1,9-nor-17~-pregna-1,3,5(10)-trien-20yn-3,17
diol (=ethinylestradiol).

:


21~ 37

Androgenically active steroid hormones, such as 17~-hydroxy-
4 androsten-3-one (=testosterone) and its esters~or 17~-hydroxy-
l~-methyl-5~-androsten-3-one (=mesterolone).
Antiandrogenically active steroid hormones, such as 17
acetoxy-6-chloro-l~r2~-dihydro-3H-cyclopropa[l~2]-pregna-l~4~6
triene-3,20-dione (=cypoterone acetate).
Corticoids, such as 11~,17a,21-trihydroxy-4-pregnene-3,20-
dione (chydrocortisone), 11~,17~,21-trihydroxy-1,4-pregnadiene-
3,20-dione (=prednisolone), 11~,17~,21-trihydroxy-6~-methyl-1,4-
pregnatriene-3,20-dione (=methyl prednisolone) and 6~-fluoro-
11~,21-dihydroxy-16~-methyl-1,4-pregnadiene-3,20-dione
(~diflucortolone) and its esters.
Suitable active ingredients are further~
Ergoline derivatives, such as lisuride [=3-(9,10-didehydro-
6-methyl-8a-ergolinyl)-1,1-diethylurea], bromolisuride t=3-(2-
bromo-9~lo-dehydro-6-methyl-8a-ergolinyl-l~l-diethylurea]~
terguride t=3-(6-methyl-8~-ergolinyl~ diethylurea] and
proterguride t=3-(6-propyl-8~-ergolinyl)-1,1-diethylurea].
Antihypertensive agents, such as 7~-acetylthio-17-hydroxy-
3-oxo-4-pregnene-21-carboxylic acid-~-lactone (=spironolactone)
and 7~-acetylthio-15~,16~-methylene-3-oxo-17~-pregna-1,4-diene-
21,17-carbolactone (=mespirenone).
Anticoagulants, such as 5~[hexahydro-5-hydroxy-4-(3-hydroxy-
4-methyl-1-octen-6-ynyl)-2(lH)-pentalenylidene)]-pentanoic acid
(~iloprost) or (Z)-7-[(lR,2R,3R,5R)-5-chloro-3-hydroxy-2-[(E)-
(3R)-3-hydroxy-4,4-dimethyl-l-octenyl]-cyclopentyl]-5-heptenoic
acid (=nocloprost).


`\
2 ~ 3 7
Psychopharmaceutical agents, such as 4-(3-cyclopentyloxy-4-
methoxy-phenyl-2-pyrrolidone (=rolipram) and 7-chloro-1,3-
dihydro-l-methyl-s-phenyl-2H-1,4-benzodiazepin-2-one (=diazepam).
Organic nitro compounds, such as nitroglycerine or
isosorbide dinitrate t=l,4,3,6-dianhydro-D-glucitol-dinitrate].
Beta-blockers, such as propanolol ~ [(l-methylethyl)-
amino]-3-~l-naphthyloxy-2-propanolol}r mepindolol ~=i-[(l-
methylethyl)-amino]-3-~(2-methyl-lH-inol-4-yl)-oxy]-2-propanol~
and carazolol ~=2-(sH-carbazol-4-yloxy)-3-t(l-methethyl)-amino]
2-propanol}.
Carotenoids, such as ~-carotene and ~-carotene.
~-Carbolines are another group, as they are described, for ; ;~
example, in European Patent Applications 234,173 and 239,667. As
~-carbolines, there can be mentioned, for example, 6-benzoyloxy-
4-methoxymethyl-~-carboline-3-carboxylic acid-isopropylester
. . .
~-becarnil) and 5-(4-chlorophenoxy)-4-methoxymethyl-~-carboline-
3-carboxylic acid-isopropylester (=Cl-PHOCIP~.
Also worth mentioning are analgesics, such as, for example,
salicylic acid, glycol salicylate, methyl salicylate, 7,8-
didehydro-4,5-epoxy-17-methyl-morphinan-3,6-diol (=morphine),
4,5-epoxy-14-hydroxy-3-methoxy-17-methyl-morphinan-6-one
(oxycodone), (-)-(R)-6-(dimethylaminol-4,4-diphenyl-3-heptanone
(=levomethadone) or 3,4,5,6-tetrahydro-5-methyl-1-phenyl-lH-2,5-
benzoxacin (=nefopam).
Finally, nicotine, clonidine and scopolamine can be
mentioned as suitable active ingredients.


: .
~' ,'.:'.



3~1

It is plausible that ~he transdermal systems according to -
the invention can also contain mixtures of these-active
ingredients.
The optimal concentration of the active ingredient in the
transdermal therapeutic systems according to the invention is, of
course, dependent on the type of active ingredient, its
effectiveness, the type of penetration enhancer, the adhesive
used, etc., and must be determined in the individual case by the
preliminary tests familiar to the galenic specialist. Usually,
he will proportion the active ingredient so that its
concentration in the finished matrix is 0.1 to 10% by weight ~ `
relative to the latter.
The transdermal therapeutic systems according to the
invention are pre*erably constituted so that they consist of a
top coating impermeable to the penetration enhancer and
optlonally also to water, an adhesive matrix containing an active
ingredient adhering to the top coating, which contains polar and
nonpolar penetration enhancers, and a removable protective layer.
This simplest form of a transdermal therapeutic system,
which i5 designated as an adhesive matrix-TTS, can be produced in
the way that a solution of adhesive is mixed in a low-boiling
solvent with the active ingredient or active ingredient mixture,
the polar and the nonpolar penetration enhancer, the mixture is
applied in sheets to a top coating impermeable to the penetration
enhancer and optionally also to water, the volatile solvent is
removed by heating and the obtained product is covered with a
removable protective layer.


--~ 8 211~1~37

Suitable solvents for dissolving the adhesive are, for
example, low-boiling alcohols, such as methanol~ ethanol or
isopropanol, low-boiling ketones, such as acetone, low-boiling
hydrocarbons, such as hexane, or low-boiling esters, such as
ethyl acetate as well as their mixtures.
This process can be performed in the way that a solution or
: .
suspension of the active ingredient, the penetration enhancer and -~
the adhesive in a volatile solvent are spread on a flat,
impermeable top coating and after the drying at about 60C to
90C are provided with a removable protective layer.
As protective layers, all films are suitable which are
usually used with adhesive in transdermal therapeutic systems.
Such films are, for example, siliconized or coated with
fluoropolymer.
As a top coating, for example, 10 to 100 ~m thick films made
oP polyethylene, PVC, PVDC or their copolymers or polyesters can
be used alternatively pigmented or metallized. The
pharmaceutical agent layer applied upon this preferably has a
thickness of 20 to 500 ~m. The active ingredients are delivered
preferably over an area of 5 to 100 cm2.
It is obvious to one skilled in the art that the transdermal
therapeutic systems according to the invention can also be
con~igured significantly more complex than the already mentioned
simple matrix systems. (Yie W. Chien: "Transdermal Controlled
Systemic Medications," Marcel Dekker, Inc., New York and Basel,
1987, Dr. Richard Baker: "Analysis of Transdermal Drug Delivery
Patents 1934 to 1984" and "Analysis of Recent Transdermal




,. .. .


2 ~ 3 7
Delivery Patents, 1984-1986 and Enhancers," Membrane Technology
Research, 1030 Hamilton Court, Menlo Park, CA 94025 (415) 328-

2228). But this should generally provide no significant ~.
advantages of the systems whatsoever, which warrant the increased ~ ~:
expense in their production.
The following embodiment is used to explain the invention in -
more detail:


~ ~ 10 2 ~ 3 r~ :

Example 1 -
To 100 g of a 50% by weight solution of silicone adhesive
X7-4~02 (manufacturer: Dow Corning Comp.) in hexane are added in
succession
3.00 g of 17~-estradiol
6.00 g of 1,2-propanediol and ~ `
1.00 g of isopropyl myristate.
The cloudy mass which forms is then rolled in a high-grade steel
vessel to remove existing gas bubbles.
The mass that is largely free of gas bubbles is applied to a
fluoropolymer-coated polyester film (Scotchpack~R) 1022 of the 3M
company, Minneapolis) or a siliconized film (Akrosil Silox B 54
of the Akrosil company, Comp.) by a knife-over-roll coating
device in the way that after the removal of the volatile solvent
at 65-75C over 2 to 3 minutes, a uniform film of 50 g/m2
results. Then, it is laminated with a polyester cover film
~Hytrel 6108 film 30 ~m -- of the Bertek company, Vermont/USA).
The thus obtained laminate is divided by a punching device into
individual patche6 of 5 cm2, 10 cm2 and 20 cm2 areas and packed in ;~`
aluminized bags. After removal of the protective film, the
patches adhere to the skin and can be used for hormone
replacement.



Exam~le 2
To 100 g of a 50% by weight solution of acrylate adhesive
Gelva~R) (manufacturer: Monsanto Comp.) in ethyl acetate are added

' i"'

2 1 ~ 7 ~ ~
in succession
3.00 g of 17~-estradiol -

6.00 g of micronized urea, dispersed in hexane and -
3.00 g of isopropyl myristate.
The cloudy mass which forms is then rolled in a high-grade steel
vessel to remove existing gas bubbles.
The mass that is largely free of gas bubbles is applied to a
fluoropolymer-coated polyester film (Scotchpack~R) 1022 of the 3M
company, Minneapolis) or a siliconized film (Akrosil Silox B 54
of the Akrosil company, Comp.) by a knife-over~roll coating
device ln the way that after the removal of the volatile solvent
at 65-75C over 2 to 3 minutes, a uniform film of 50 g/m2
results. ~hen, it is laminated with a polyester cover film
(Hytrel 6108 film 30 ~m -- of the Bertek company, Vermont/USA).
The thus obtained laminate is divided by a punching device into
individual patches of 5 cm2, 10 cm2 and 20 cm2 area and packed in
aluminized bags. After removal of the protective film, the
patches adhere to the skin and can be used for hormone
replacement.



Example 3
To 100 g of a 50% by weight solution of silicone adhesive
X7-4502 (manufacturer: Dow Corning Comp.) in hexane are added in
succession
3.00 g of 17~-estradiol
5.00 g of micronized urea, dispersed in hexane and
2.00 g of isopropyl myristate.
- ' ~

12
~-` 2 1 t ~ 7
~ .
The cloudy mass which forms is then rolled in a high-grade steel ~ ;
vessel to remove existing gas bubbles. -
The mass that is largely free of gas bubbles is applied to a -
. .
fluoropolymer-coated polyester film (Scotchpack~R) 1022 of the 3M
company, Minneapolis) or a siliconized film (Akrosil Silox B 54
of the Akrosil company, Comp.) by a knife-over-roll coating -
device in the way that after the removal of the volatile solvent
at 65-75C over 2 to 3 minutes, a uniform film of 50 g/m2
results. Then, it is laminated with a polyester cover film
(Hytrel 6108 film 30 ~m -- of the Bertek company, Vermont/USA).
The thus obtained laminate is divided by a punching device into
individual patches of 5 cm2, lO cm2 and 20 cm2 areas and packed in --
aluminized bags. After removal of the protective film, the
patches adhere to the skin and can be used for hormone
replacement.
, .
.~




- " ,.. ~ .~

Dessin représentatif

Désolé, le dessin représentatatif concernant le document de brevet no 2114537 est introuvable.

États administratifs

Pour une meilleure compréhension de l'état de la demande ou brevet qui figure sur cette page, la rubrique Mise en garde , et les descriptions de Brevet , États administratifs , Taxes périodiques et Historique des paiements devraient être consultées.

États administratifs

Titre Date
Date de délivrance prévu Non disponible
(86) Date de dépôt PCT 1992-07-07
(87) Date de publication PCT 1993-02-18
(85) Entrée nationale 1994-01-28
Requête d'examen 1999-05-26
Demande morte 2004-07-07

Historique d'abandonnement

Date d'abandonnement Raison Reinstatement Date
2001-07-09 Taxe périodique sur la demande impayée 2001-11-14
2003-07-07 Taxe périodique sur la demande impayée
2003-10-27 R30(2) - Absence de réponse

Historique des paiements

Type de taxes Anniversaire Échéance Montant payé Date payée
Le dépôt d'une demande de brevet 0,00 $ 1994-01-28
Taxe de maintien en état - Demande - nouvelle loi 2 1994-07-07 100,00 $ 1994-07-05
Enregistrement de documents 0,00 $ 1994-07-26
Taxe de maintien en état - Demande - nouvelle loi 3 1995-07-07 100,00 $ 1995-06-20
Taxe de maintien en état - Demande - nouvelle loi 4 1996-07-08 100,00 $ 1996-06-18
Taxe de maintien en état - Demande - nouvelle loi 5 1997-07-07 150,00 $ 1997-06-23
Taxe de maintien en état - Demande - nouvelle loi 6 1998-07-07 150,00 $ 1998-06-29
Requête d'examen 400,00 $ 1999-05-26
Taxe de maintien en état - Demande - nouvelle loi 7 1999-07-07 150,00 $ 1999-06-28
Taxe de maintien en état - Demande - nouvelle loi 8 2000-07-07 150,00 $ 2000-06-29
Rétablissement: taxe de maintien en état non-payées pour la demande 200,00 $ 2001-11-14
Taxe de maintien en état - Demande - nouvelle loi 9 2001-07-09 150,00 $ 2001-11-14
Taxe de maintien en état - Demande - nouvelle loi 10 2002-07-08 200,00 $ 2002-07-08
Titulaires au dossier

Les titulaires actuels et antérieures au dossier sont affichés en ordre alphabétique.

Titulaires actuels au dossier
SCHERING AKTIENGESELLSCHAFT
Titulaires antérieures au dossier
HARTISCH, MATTHIAS
LIPP, RALPH
RIEDL, JUTTA
Les propriétaires antérieurs qui ne figurent pas dans la liste des « Propriétaires au dossier » apparaîtront dans d'autres documents au dossier.
Documents

Pour visionner les fichiers sélectionnés, entrer le code reCAPTCHA :



Pour visualiser une image, cliquer sur un lien dans la colonne description du document. Pour télécharger l'image (les images), cliquer l'une ou plusieurs cases à cocher dans la première colonne et ensuite cliquer sur le bouton "Télécharger sélection en format PDF (archive Zip)" ou le bouton "Télécharger sélection (en un fichier PDF fusionné)".

Liste des documents de brevet publiés et non publiés sur la BDBC .

Si vous avez des difficultés à accéder au contenu, veuillez communiquer avec le Centre de services à la clientèle au 1-866-997-1936, ou envoyer un courriel au Centre de service à la clientèle de l'OPIC.


Description du
Document 
Date
(yyyy-mm-dd) 
Nombre de pages   Taille de l'image (Ko) 
Description 2002-06-18 12 836
Revendications 2002-06-18 2 64
Page couverture 1995-05-27 1 126
Abrégé 1995-05-27 1 67
Revendications 1995-05-27 2 143
Description 1995-05-27 12 987
Cession 1994-01-28 6 324
PCT 1994-01-28 20 722
Poursuite-Amendment 1999-05-26 1 33
Poursuite-Amendment 2001-12-19 2 61
Poursuite-Amendment 2002-06-18 7 227
Poursuite-Amendment 2003-04-25 3 121
Taxes 1996-06-18 1 58
Taxes 1995-06-20 1 62
Taxes 1994-07-05 1 48