EP0679106A1 - Device for the dermal absorption of medicinal solutes - Google Patents

Device for the dermal absorption of medicinal solutes

Info

Publication number
EP0679106A1
EP0679106A1 EP92915288A EP92915288A EP0679106A1 EP 0679106 A1 EP0679106 A1 EP 0679106A1 EP 92915288 A EP92915288 A EP 92915288A EP 92915288 A EP92915288 A EP 92915288A EP 0679106 A1 EP0679106 A1 EP 0679106A1
Authority
EP
European Patent Office
Prior art keywords
plug
skin
solute
balloon
notch
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP92915288A
Other languages
German (de)
French (fr)
Inventor
Fred Cabrera
Jean Perego
Francois-Xavier Sarzaud
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SARZAUD FRANCOIS XAVIER
Original Assignee
SARZAUD FRANCOIS XAVIER
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by SARZAUD FRANCOIS XAVIER filed Critical SARZAUD FRANCOIS XAVIER
Publication of EP0679106A1 publication Critical patent/EP0679106A1/en
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches

Definitions

  • the present invention relates to the field of transdermal drug application systems and relates to an improved device for the administration, by the dermal route, of drug solutes.
  • FICK (as well as STOCK and STEIN) according to which the speed of migration is a function of the concentration gradient between two compartments, the molecules going from the most concentrated to the least concentrated.
  • the speed decreases when the viscosity of the medium increases or when the permeability is low.
  • the reservoir containing the active ingredient solute is closed by a membrane applied to the skin and permeable only to the active ingredient.
  • This membrane is covered with an adhesive making it possible to fix the tampon on the skin and to offer a solution of continuity with the latter.
  • the tank is replaced by an absorbent mass, a kind of sponge
  • REPLACEMENT SHEET molecular which can be the adhesive mass itself.
  • the face applied to the skin is also adhesive and provides a surface for continuity with the skin.
  • the matrix as well as the membrane and the adhesive act as barriers which considerably slow down the migration of the active principle towards the skin.
  • the flow of active product which migrates into the skin still has the appearance over time, of an inverted exponential.
  • the adhesive which serves as a continuity solution for the migration of the active product requires several hours to adhere, due to the adaptation to the relief of the skin, which creates a delay in the therapeutic effect.
  • the adhesive forms a so-called occlusive area on the surface of the skin, that is to say that the adhesive prevents the evaporation of sweat. If the active ingredient is not soluble in water (for example, trinitrine and estradiol), this occlusion effect considerably disrupts, or even prevents, migration. Finally, this same effect is at the origin of the takeoff and the fall of the tampon or lozenge, which can be dramatic for the patient, for example in the event of myocardial infarction.
  • the invention aims to eliminate these series of drawbacks and aims to propose a new transdermal application system requiring a set of qualities and advantages not achieved to date, including in particular: effectiveness; reliability at low cost; the absence of adhesive on the part of the skin receiving the active product; obtaining self-regulating flow despite variations in skin permeability (over time and depending on the patient) and the possibility of regular deposition of active product for a period of 8 days, 15 days or more.
  • the device according to the invention for the administration by the transcutaneous route of medicinal solutes is essentially characterized in that it comprises: a) a reservoir or application bowl, the base of which is provided with an orifice filling for the solute as well as a cutout with cap provided on its periphery with micro-recesses for the distribution of the solute on the skin; b) means for pressurizing and regulating the flow of solute inside the tank; c) a cover for sealing said tank.
  • micro-recesses may be, according to the invention, designed in several non-limiting ways.
  • the micro-recesses are formed by the roughness obtained when the plug is produced by molding the electro-erosion technique.
  • roughness indices can be adopted which can vary between No. 33 and No. 21, which corresponds to maximum distances or heights between the peaks or troughs of the recesses from 4.5 to 1.2 microns.
  • the stopper has a generally conical configuration in which a conical head can be provided, the first diameter of which corresponds to the diameter of the body of the stopper.
  • the micro-recesses are constituted by a notch on the stopper constituting a mini-notch formed parallel to the axis of the stopper and forming an annular channel which ends, on the side in contact with the skin, by a flare whose shape is substantially triangular.
  • the active principle of solute through 1 "echancrur circulates around the perimeter of the perimeter capillary then broadcasts on 1'ensemble of the area covered.
  • the pressure means is constituted according to a first variant by a balloon based on a plastic film complex and filled with a mixture of freons.
  • This balloon or hollow volume is advantageously - although not exclusively - constituted by a polyethylene film bonded to a polyamide film by means of an adhesive constituted, for example, by a two-component polyurethane adhesive.
  • this balloon can be replaced by a film, simple or complex above, of plastic material not constituting a volume.
  • a seal intended both to ensure the seal and to exert pressure on said film during closing. of the device.
  • the balloon contains a mixture of freons which is either in the gaseous state or in the liquid state depending on the conditions of use (application of the tablet or storage of the latter in the cold).
  • said mixture liquid at ordinary temperature, is deposited on the internal wall of the reservoir.
  • freons freon 11 and freon 113, in substantially equal proportions.
  • the pressure means can also be constituted according to a second advantageous variant of the invention by a spring resting on a plastic film.
  • This film can be folded back on itself, in the form of a bellows where it can be constituted by a hollow volume of the balloon type. In both cases, it comes to bear, by the action of the spring on the upper face of the reservoir, containing the solute.
  • Fig. 1 a general view, in section, of a device according to the first alternative embodiment
  • - Fig. 2 another embodiment of the internal part of the device
  • - Fig. 3 a top view of the device
  • - Fig. 4 and 5 representations, respectively in perspective and in section, of a plug with rough walls, obviously provided with a microphone
  • - Fig. 6 a representation of a notch for flow, made on one edge of the plug
  • - Fig. 7 an enlarged embodiment of a widening of a notch in the form of an equilateral triangle
  • - Fig. 8 a general sectional view of the device according to the second alternative embodiment.
  • a device essentially comprises: a reservoir 1 or application cup, into which a balloon or a plastic film 2 is introduced, and a lid 3 for sealing .
  • the wall of the reservoir is provided with a filling orifice 4 (with closure cap, not shown) and with a plug 5 of conical shape.
  • FIGS. 4 and 5 illustrate an advantageous embodiment of a plug 5 provided with a conical head and the external faces of which are provided with roughness 13 obtained during electro-erosion molding and corresponding to roughness indices, for example between the n ° 39 and 21.
  • FIG. 6 shows a type of plug, still with a conical head, where the means for the flow of the active flux is no longer constituted by the micro-recesses due to the surface roughness but by a notch 6 terminated by a flaring 7.
  • Figure 7 shows an embodiment of the base of the notch in the form of an equilateral triangle.
  • a coarse adjustment is first carried out by attacking one of the faces of the triangle, for example face 8 (fig. 6) by wearing the mini-slices X then Y then Z. Then, for an additional adjustment in addition, the vertex 9 is attacked, for example along the mini-slabs A, B, C ... E.
  • a pressure medium intended to slightly compress, under a pressure which can vary for example from 5.10 3 to 5.10 4 Pascals (Pa), the medicated solution on the stopper 5 and force the latter to flow through the roughness 13 or to engage in the notch 6.
  • this means is constituted by the balloon 2 made of plastic film welded on the edges and cut in a circle.
  • the plastic film is advantageously constituted by a complex based on polyethylene bonded to the polyamide film with a polyurethane adhesive.
  • the inner periphery of the cover 3 is provided with a seal 10, for example made of silicone, intended to seal and to wedge a plastic film 11 playing the role of balloon. The cover then acts here as one of the walls of the balloon.
  • the balloon is filled with a mixture of freons and, in the case of the variant, fig. 2, the mixture in question is deposited on the wall of the cover.
  • a mixture for example in substantially equal proportions of freon 11 and freon 113, makes it possible to obtain very low pressures of the order of 2.10 4 Pa and does not give rise to any measurable leak, even after one year.
  • the drug solute also advantageously contains, in addition to the freons, propylene glycol: this gives a perfect balance of the vapor pressures as well as of migration of the solute when the pad or tablet is at ordinary temperature.
  • FIG. 8 illustrates a particularly advantageous embodiment of the pressure means and regularization of the flow of the solute.
  • the solute tank 1 provided with a conical cap 5, and an opening for filling (located at the rear of said plug and not shown in the figure), constitutes the bearing surface of a bellows (15), made of folded plastic film (or possibly in the form of a balloon).
  • a bellows made of folded plastic film (or possibly in the form of a balloon). The gradual release of the solute is done by the permanent support of the spring (14) on the bellows (15).
  • each constituent element of the device according to the invention takes a similar shape, extra flat and can be made of plastic material by compression molding, using the electro-erosion technique, as said above, for the impressions of the plug and surface roughness or, depending on the variant, the notch.
  • the device is often provided with adhesive parts 12 and 17 for attachment to the skin. But it can be used in other forms such as for example in the form of a bracelet or even a belt for application to the abdomen (in particular for the trinitrin solutions used as coronarodilators in 1 • myocardial infarction). It is of course possible to produce the device of the invention according to various dimensions. By way of nonlimiting example, experiments have been carried out according to the first embodiment of FIGS.
  • the extra-flat spring (14) applied with a force of the order of 0.9 kg on the bellows (15) and therefore on the solute.
  • the systems according to the invention are self-regulating.
  • the surface of the skin which will absorb the solute will be all the smaller, the higher the permeability of the skin to the active principle.

Abstract

The device comprises: a) a delivery container or receptacle (1) of which the bottom is provided with a solute filling opening (4) and a cut-out with a plug (5) provided with peripheral micro-recesses for delivering solute to the skin; b) an element (2) for pressurizing and regulating the flow of solute within the container; and c) a lid (3) for sealing the container. The device may be used as a wristband, abdominal girdle or patch for delivering solutes such as trinitrin, estradiols etc. to the skin.

Description

Dispositif pour l'absorption dermique de solutés médicamenteux.Device for the dermal absorption of medicinal solutes.
La présente invention a trait au domaine des systèmes transdermigues d'applications de médicament et concerne un dispositif perfectionné pour l'administration, par voie cutanée, de solutés médicamenteux.The present invention relates to the field of transdermal drug application systems and relates to an improved device for the administration, by the dermal route, of drug solutes.
On connaît et l'on a développé et commercialisé depuis quelques années des systèmes et dispositifs, présentés sous la forme de tampons ou pastilles (terme anglais courant "patch") qui sont collés sur la peau et contiennent des solutés médicamenteux à divers principes actifs, qui sont aptes à délivrer le médicament adéquat à de très faibles doses, par exemple 1 microgramme à 20 mg par jour pendant 2 à 30 jours ou plus. On peut citer par exemple, entre autres applications, l'administration de trinitrine, pour les maladies du coeur, d'estradiol pour le traitement de la ménopause, etc ...Systems and devices have been known and developed and marketed for a few years, presented in the form of tampons or lozenges (common English term "patch") which are bonded to the skin and contain medicinal solutions with various active ingredients, that are capable of delivering the correct medication at very low doses, for example 1 microgram to 20 mg per day for 2 to 30 days or more. We can cite for example, among other applications, the administration of trinitrine, for heart diseases, estradiol for the treatment of menopause, etc.
Les systèmes connus sont actuellement de deux types, ceux à membranes et ceux dits "à matrice", et utilisent le principe de migration régi par la loi deThe known systems are currently of two types, those with membranes and those known as "with matrix", and use the principle of migration governed by the law of
FICK (ainsi que STOCK et STEIN) selon laquelle la vitesse de migration est fonction du gradient de concentration entre deux compartiments, les molécules allant du plus concentré au moins concentré. La vitesse diminue lorsque la viscosité du milieu augmente ou quand la perméabilité est faible.FICK (as well as STOCK and STEIN) according to which the speed of migration is a function of the concentration gradient between two compartments, the molecules going from the most concentrated to the least concentrated. The speed decreases when the viscosity of the medium increases or when the permeability is low.
Dans le système à membrane, le réservoir contenant le soluté de principe actif est fermé par une membrane appliquée sur la peau et perméable uniquement au principe actif. Cette membrane est recouverte d'un adhésif permettant de fixer le tampon sur la peau et d'offrir une solution de continuité avec cette dernière.In the membrane system, the reservoir containing the active ingredient solute is closed by a membrane applied to the skin and permeable only to the active ingredient. This membrane is covered with an adhesive making it possible to fix the tampon on the skin and to offer a solution of continuity with the latter.
Dans le système à matrice, le réservoir est remplacé par une masse absorbante, sorte d'épongéIn the matrix system, the tank is replaced by an absorbent mass, a kind of sponge
FEUILLE DE REMPLACEMENT moléculaire, qui peut être la masse adhesive elle-même. La face appliquée sur la peau est également adhesive et offre une surface de continuité avec la peau.REPLACEMENT SHEET molecular, which can be the adhesive mass itself. The face applied to the skin is also adhesive and provides a surface for continuity with the skin.
Dans de tels systèmes, la matrice ainsi que la membrane et l'adhésif jouent le rôle de barrières qui freinent considérablement la migration du principe actif vers la peau. Malgré l'effet de régulation recherché, le flux de produit actif qui migre dans la peau a toujours l'allure dans le temps, d'une exponentielle inversée. On a donc besoin, dans le système, de fortes concentrations en principe actif pour obtenir une pression locale relativement forte ; il convient ensuite de freiner la migration afin d'obtenir un flux ayant toujours l'allure d'une exponentielle inversée mais fortement atténuée. En effectuant des séries de mesures de taux de migration et d'absorption, on a pu ainsi constater que, pour des pastilles à membrane et à matrice devant délivrer des quantités voulues de produit actif de 20 à 25 mg à raison de 5 mg par jour, on avait des rendements de l'ordre de 20 à 30 % environ seulement.In such systems, the matrix as well as the membrane and the adhesive act as barriers which considerably slow down the migration of the active principle towards the skin. Despite the desired regulatory effect, the flow of active product which migrates into the skin still has the appearance over time, of an inverted exponential. There is therefore a need, in the system, for high concentrations of active principle in order to obtain a relatively high local pressure; it is then necessary to slow down the migration in order to obtain a flow always having the appearance of an inverted but strongly attenuated exponential. By carrying out series of migration and absorption rate measurements, it has thus been found that, for membrane and matrix pellets having to deliver desired quantities of active product from 20 to 25 mg at a rate of 5 mg per day , we had yields of around 20 to 30% only.
D'autre part, l'adhésif qui sert de solution de continuité pour la migration du produit actif demande plusieurs heures pour adhérer, du fait de l'adaptation au relief de la peau, ce qui créé un retard dans l'effet thérapeutique. Par ailleurs, il arrive fréquemment de constater, après adhérence de l'adhésif, un surdosage du produit pendant une à deux heures du fait de la migration, sur une très courte distance, des molécules se trouvant à proximité de la surface en contact avec la peau. L'adhésif forme sur la surface de la peau une zone à effet dit occlusif, c'est-à-dire que l'adhésif empêche 1'évaporation de la sueur. Si le principe actif n'est pas soluble dans l'eau (par exemple, cas de la trinitrine et de l'estradiol) , cet effet d'occlusion perturbe considérablement, voir même empêche, la migration. Enfin, ce même effet est à l'origine du décollage et de la chute du tampon ou pastille, ce qui peut être dramatique pour le patient, par exemple en cas d'infarctus du myocarde.On the other hand, the adhesive which serves as a continuity solution for the migration of the active product requires several hours to adhere, due to the adaptation to the relief of the skin, which creates a delay in the therapeutic effect. In addition, it frequently happens to observe, after adhesion of the adhesive, an overdose of the product for one to two hours due to the migration, over a very short distance, of the molecules being close to the surface in contact with the skin. The adhesive forms a so-called occlusive area on the surface of the skin, that is to say that the adhesive prevents the evaporation of sweat. If the active ingredient is not soluble in water (for example, trinitrine and estradiol), this occlusion effect considerably disrupts, or even prevents, migration. Finally, this same effect is at the origin of the takeoff and the fall of the tampon or lozenge, which can be dramatic for the patient, for example in the event of myocardial infarction.
L'invention vise à supprimer ces séries d'inconvénients et a pour but de proposer un nouveau système d'application transdermique nécessitant un ensemble de qualités et avantages non atteints à ce jour dont en particulier : l'efficacité; la fiabilité pour un coût peu élevé; l'absence d'adhésif sur la partie de la peau recevant le produit actif; l'obtention d'une autorégulation de flux malgré les variations de perméabilité de la peau (dans le temps et selon les patients) et la possibilité d'un dépôt régulier de produit actif pendant une durée de 8 jours, 15 jours ou plus.The invention aims to eliminate these series of drawbacks and aims to propose a new transdermal application system requiring a set of qualities and advantages not achieved to date, including in particular: effectiveness; reliability at low cost; the absence of adhesive on the part of the skin receiving the active product; obtaining self-regulating flow despite variations in skin permeability (over time and depending on the patient) and the possibility of regular deposition of active product for a period of 8 days, 15 days or more.
Pour résoudre ces problèmes, le dispositif selon l'invention pour l'administration par voie transcutanée de solutés médicamenteuses est essentiellement caractérisé en ce qu'il comprend : a) un réservoir ou cuvette d'application dont la base est munie d'un orifice de remplissage pour le soluté ainsi que d'une découpe avec bouchon pourvu sur sa périphérie de micro-évidements pour la distribution du soluté sur la peau ; b) un moyen pour pressuriser et régulariser le débit de soluté à l'intérieur du réservoir ; c) un couvercle pour la fermeture étanche dudit réservoir.To solve these problems, the device according to the invention for the administration by the transcutaneous route of medicinal solutes is essentially characterized in that it comprises: a) a reservoir or application bowl, the base of which is provided with an orifice filling for the solute as well as a cutout with cap provided on its periphery with micro-recesses for the distribution of the solute on the skin; b) means for pressurizing and regulating the flow of solute inside the tank; c) a cover for sealing said tank.
La réalisation des micro-évidements peut-être, selon l'invention, conçue de plusieurs façons non limitatives.The production of micro-recesses may be, according to the invention, designed in several non-limiting ways.
Conformément à un premier mode d'exécution, les micro-évidements sont constitués par les rugosités obtenues lorsqu'on réalise par moulage le bouchon selon la technique d*électro-érosion. En pratique, on peut adopter des indices de rugosité pouvant varier entre le n° 33 et le n° 21, ce qui correspond à des distances maximales ou hauteurs entre les pics ou les creux des évidements de 4,5 à 1,2 microns. Avantageusement, le bouchon est de configuration générale conique où peut comporter une tête conique dont le premier diamètre correspond au diamètre du corps du bouchon.In accordance with a first embodiment, the micro-recesses are formed by the roughness obtained when the plug is produced by molding the electro-erosion technique. In practice, roughness indices can be adopted which can vary between No. 33 and No. 21, which corresponds to maximum distances or heights between the peaks or troughs of the recesses from 4.5 to 1.2 microns. Advantageously, the stopper has a generally conical configuration in which a conical head can be provided, the first diameter of which corresponds to the diameter of the body of the stopper.
Selon un autre mode de réalisation, les micro-évidements sont constitués par une echancrure sur le bouchon constituant une mini-encoche pratiquée parallèlement à l'axe du bouchon et formant un canal annulaire qui se termine, du côté en contact avec la peau, par un évasement dont la forme est sensiblement triangulaire. Grâce à cette configuration, sur laquelle on reviendra plus loin, le soluté de principe actif traverse 1»echancrur , circule sur le périmètre du pourtour par capillarité puis diffuse sur 1'ensemble de l'aire couverte. Conformément à l'invention, le moyen de pression est constitué selon une première variante par un ballonnet à base d'un complexe de film de matière plastique et rempli d'un mélange de fréons.According to another embodiment, the micro-recesses are constituted by a notch on the stopper constituting a mini-notch formed parallel to the axis of the stopper and forming an annular channel which ends, on the side in contact with the skin, by a flare whose shape is substantially triangular. With this configuration, which will be discussed further, the active principle of solute through 1 "echancrur circulates around the perimeter of the perimeter capillary then broadcasts on 1'ensemble of the area covered. According to the invention, the pressure means is constituted according to a first variant by a balloon based on a plastic film complex and filled with a mixture of freons.
Ce ballonet ou volume creux est avantageusement - quoique non exclusivement - constitué par un film de polyéthylène collé sur un film de polyamide au moyen d'un adhésif constitué, par exemple, par une colle polyuréthanne à deux composants. Toutefois, selon une variante de réalisation, ce ballonnet peut être remplacé par un film, simple ou complexe ci-dessus, en matière plastique ne constituant pas un volume. Dans ce cas, on prévoit, pour la périphérie interne du couvercle, un joint destiné à assurer à la fois l'étanchéité et à exercer une pression sur ledit film lors de la fermeture du dispositif.This balloon or hollow volume is advantageously - although not exclusively - constituted by a polyethylene film bonded to a polyamide film by means of an adhesive constituted, for example, by a two-component polyurethane adhesive. However, according to an alternative embodiment, this balloon can be replaced by a film, simple or complex above, of plastic material not constituting a volume. In this case, there is provided, for the inner periphery of the cover, a seal intended both to ensure the seal and to exert pressure on said film during closing. of the device.
Comme dit ci-dessus, le ballonnet renferme un mélange de fréons qui se trouve soit à l'état gazeux soit à l'état liquide selon les conditions d'utilisation (application de la pastille ou conservation de cette dernière au froid) . Dans le cas de la variante précitée où le ballonnet est remplacé par un film, ledit mélange, liquide à température ordinaire, est déposé sur la paroi interne du réservoir. En pratique, on peut adopter, comme types de fréons : le fréon 11 et le fréon 113, en proportions sensiblement égales.As said above, the balloon contains a mixture of freons which is either in the gaseous state or in the liquid state depending on the conditions of use (application of the tablet or storage of the latter in the cold). In the case of the aforementioned variant where the balloon is replaced by a film, said mixture, liquid at ordinary temperature, is deposited on the internal wall of the reservoir. In practice, it is possible to adopt, as types of freons: freon 11 and freon 113, in substantially equal proportions.
Conformément à une autre caractéristique de l'invention, on prévoit d'utiliser en mélange avec les solutés médicamenteux appliqués à 1'aide du dispositif de l'invention, une petite quantité de mélange de fréon et propanediol-1,2. Cet ajout permet d'assurer une bonne stabilisation du système de pression.According to another characteristic of the invention, provision is made to use, in admixture with the medicinal solutes applied using the device of the invention, a small amount of mixture of freon and 1,2-propanediol. This addition ensures good stabilization of the pressure system.
Le moyen de pression peut aussi être constitué selon une seconde variante intéressante de l'invention par un ressort s'appuyant sur un film en matière plastique.The pressure means can also be constituted according to a second advantageous variant of the invention by a spring resting on a plastic film.
Ce film peut être replié sur lui-même, en forme de soufflet où il peut être constitué par un volume creux de type ballonnet. Dans les deux cas de figure, il vient s'appuyer, par l'action du ressort sur la face supérieure du réservoir, contenant le soluté.This film can be folded back on itself, in the form of a bellows where it can be constituted by a hollow volume of the balloon type. In both cases, it comes to bear, by the action of the spring on the upper face of the reservoir, containing the solute.
D'autres caractéristiques encore ressortiront de la description ci-après d'exemples de réalisation non limitatifs illustrés par les dessins annexés qui représentent schématiquement :Still other characteristics will emerge from the following description of nonlimiting exemplary embodiments illustrated by the appended drawings which schematically represent:
- Fig. 1 : une vue générale, en coupe, d'un dispositif selon la première variante de réalisation ;- Fig. 1: a general view, in section, of a device according to the first alternative embodiment;
- Fig. 2 : un autre mode de réalisation de la partie interne du dispositif ; - Fig. 3 : une vue de dessus du dispositif ;- Fig. 2: another embodiment of the internal part of the device; - Fig. 3: a top view of the device;
- Fig. 4 et 5 : des représentations, respectivement en perspective et en coupe, d'un bouchon à parois rugueuses, munnies de micro évidemment ; - Fig. 6 : une représentation d'une echancrure pour écoulement, faite sur un bord du bouchon ;- Fig. 4 and 5: representations, respectively in perspective and in section, of a plug with rough walls, obviously provided with a microphone; - Fig. 6: a representation of a notch for flow, made on one edge of the plug;
- Fig. 7 : une réalisation agrandie d'un évasement d'echancrure sous la forme d'un triangle équilatéral ;- Fig. 7: an enlarged embodiment of a widening of a notch in the form of an equilateral triangle;
- Fig. 8 : une vue générale en coupe du dispositif selon la deuxième variante de réalisation.- Fig. 8: a general sectional view of the device according to the second alternative embodiment.
Comme on peut le voir sur les figures 1 à 7, un dispositif conforme à l'invention comprend essentiellement : un réservoir 1 ou cuvette d'application, dans lequel est introduit un ballonnet ou un film plastique 2, et un couvercle 3 de fermeture étanche. La paroi du réservoir est munie d'un orifice 4 de remplissage (avec opercule de bouchage, non représenté) et d'un bouchon 5 de forme conique.As can be seen in FIGS. 1 to 7, a device according to the invention essentially comprises: a reservoir 1 or application cup, into which a balloon or a plastic film 2 is introduced, and a lid 3 for sealing . The wall of the reservoir is provided with a filling orifice 4 (with closure cap, not shown) and with a plug 5 of conical shape.
De nombreuses études, effectuées dans le cadre de a présente invention en vue de créer un bouchon à orifice d'écoulement du flux actif de très faible section (par exemple 0,3 à 5 microns) et de grande stabilité dimensionnelle, ont permis de sélectionner des critères ou paramètres favorisant l'obtention des meilleurs résultats. Parmi ceux-ci il convient de relever : la réalisation de bouchon en nylon, polypropylène (ou plastique équivalent) par moulage par injection ; la confection de micro-évidements sur les bords et la surface externe des bouchons pour obtenir une surface rugueuse ou encore la réalisation d'une echancrure reproductible, ceci grâce à des moules obtenus par la technique d'électro-érosion ; le choix d'une echancrure dont la base, d'où s'effectuera l'écoulement du fluide actif, a une forme sensiblement triangulaire et, avantageusement, celle d'un triangle équilatéral.Numerous studies, carried out within the framework of the present invention with a view to creating a plug with an orifice for the flow of the active flux of very small section (for example 0.3 to 5 microns) and of great dimensional stability, have made it possible to select criteria or parameters promoting the best results. Among these it should be noted: the production of nylon, polypropylene (or equivalent plastic) plugs by injection molding; making micro-recesses on the edges and the external surface of the plugs to obtain a rough surface or even producing a reproducible notch, this using molds obtained by the electro-erosion technique; the choice of a notch whose base, from which the flow of the active fluid will take place, has a shape substantially triangular and, advantageously, that of an equilateral triangle.
Les figures 4 et 5 illustrent une réalisation avantageuse d'un bouchon 5 muni d'une tête conique et dont les faces externes sont pourvues de rugosités 13 obtenues lors du moulage par électro-érosion et correspondant à des indices de rugosité par exemple compris entre les n° 39 et 21.FIGS. 4 and 5 illustrate an advantageous embodiment of a plug 5 provided with a conical head and the external faces of which are provided with roughness 13 obtained during electro-erosion molding and corresponding to roughness indices, for example between the n ° 39 and 21.
La figure 6 montre un type de bouchon, toujours à tête conique, où le moyen d'écoulement du flux actif est non plus constitué par les micro-évidements dus à la rugosité de surface mais par une echancrure 6 terminée par un évasement 7.FIG. 6 shows a type of plug, still with a conical head, where the means for the flow of the active flux is no longer constituted by the micro-recesses due to the surface roughness but by a notch 6 terminated by a flaring 7.
La figure 7 montre une réalisation de la base de 1'echancrure sous la forme d'un triangle équilatéral. Une telle configuration permet un réglage extrêmement fin et rigoureux, lors de la réalisation de la pièce par électroérosion, des débits souhaités pour l'écoulement du fluide. Par exemple, on effectue tout d'abord un réglage grossier par attaque de l'une des faces du triangle, par exemple la face 8 (fig. 6) par usure des minitranches X puis Y puis Z. Puis, pour un réglage de plus en plus fin, on attaque le sommet 9, par exemple selon les minitranches A, B, C ... E. Bien entendu, il convient d'ajuster la surface de 1'echancrure (ou évasement) en fonction des paramètres tels que : la viscosité du soluté actif, la pression exercée par le ballonnet (comme expliqué ci-après) , la température de la peau (qui varie de 34,7 à 35,2°C). Au lieu d'un triangle équilatéral, on peut adopter un triangle dont 1'angle au sommet est plus f ,ble, par exemple de 20 degrés, ou encore une forme en demi-lune.Figure 7 shows an embodiment of the base of the notch in the form of an equilateral triangle. Such a configuration allows extremely fine and rigorous adjustment, during the production of the part by electroerosion, of the flow rates desired for the flow of the fluid. For example, a coarse adjustment is first carried out by attacking one of the faces of the triangle, for example face 8 (fig. 6) by wearing the mini-slices X then Y then Z. Then, for an additional adjustment in addition, the vertex 9 is attacked, for example along the mini-slabs A, B, C ... E. Of course, it is necessary to adjust the surface of the notch (or flare) as a function of parameters such as: the viscosity of the active solute, the pressure exerted by the balloon (as explained below), the temperature of the skin (which varies from 34.7 to 35.2 ° C). Instead of an equilateral triangle, it is possible to adopt a triangle whose angle at the top is more flexible, for example 20 degrees, or else a half-moon shape.
Selon une caractéristique fondamentale de l'invention, on utilise à l'intérieur du réservoir 1 un moyen de pression destiné à comprimer légèrement, sous une pression pouvant varier par exemple de 5.103 à 5.104 Pascals (Pa) , le soluté médicamenteux sur le bouchon 5 et forcer ce dernier à s'écouler par les rugosités 13 ou à s'engager dans l'echancrure 6. Conformément à la figure 1, ce moyen est constitué par le ballonnet 2 réalisé en film plastique soudé sur les bords et découpé en cercle. Le film plastique est avantageusement constitué par un complexe à base de polyéthylène collé sur film du polyamide par un adhésif de polyuréthane. Selon la variante de la figure 2, le pourtour interne du couvercle 3 est muni d'un joint 10, par exemple en silicone, destiné à assurer l'étanchéité et à coincer un film plastique 11 jouant le rôle de ballonnet. Le couvercle fait alors office ici d'une des parois du ballonnet.According to a fundamental characteristic of the invention, inside the tank 1 a pressure medium intended to slightly compress, under a pressure which can vary for example from 5.10 3 to 5.10 4 Pascals (Pa), the medicated solution on the stopper 5 and force the latter to flow through the roughness 13 or to engage in the notch 6. According to Figure 1, this means is constituted by the balloon 2 made of plastic film welded on the edges and cut in a circle. The plastic film is advantageously constituted by a complex based on polyethylene bonded to the polyamide film with a polyurethane adhesive. According to the variant of Figure 2, the inner periphery of the cover 3 is provided with a seal 10, for example made of silicone, intended to seal and to wedge a plastic film 11 playing the role of balloon. The cover then acts here as one of the walls of the balloon.
Le ballonnet est rempli d'un mélange de fréons et, dans le cas de la variante, fig. 2, le mélange en cause est déposé sur la paroi du couvercle. Un tel mélange, par exemple selon des proportions sensiblement égales de fréon 11 et de fréon 113, permet d'obtenir de très faibles pressions de l'ordre de 2.104 Pa et ne donne lieu à aucune fuite mesurable, même après une année. Ceci est également dû au fait que le soluté de médicament contient également, avantageusement, en plus des fréons, du propylèneglycol : on obtient ainsi un parfait équilibre des pressions de vapeur ainsi que de migration du soluté lorsque le tampon ou pastille se trouve à température ordinaire. La figure 8 illustre un mode de réalisation particulièrement avantageux du moyen de pression et régularisation du débit du soluté.The balloon is filled with a mixture of freons and, in the case of the variant, fig. 2, the mixture in question is deposited on the wall of the cover. Such a mixture, for example in substantially equal proportions of freon 11 and freon 113, makes it possible to obtain very low pressures of the order of 2.10 4 Pa and does not give rise to any measurable leak, even after one year. This is also due to the fact that the drug solute also advantageously contains, in addition to the freons, propylene glycol: this gives a perfect balance of the vapor pressures as well as of migration of the solute when the pad or tablet is at ordinary temperature. . FIG. 8 illustrates a particularly advantageous embodiment of the pressure means and regularization of the flow of the solute.
Sur cette vue en éclaté, le réservoir à soluté 1, muni d'un bouchon conique 5, et d'une ouverture de remplissage (située à l'arrière dudit bouchon et non représentée sur la figure), constitue la surface d'appui d'un soufflet (15) , en film replié de matière plastique (ou éventuellement en forme de ballonnet) . La libération progressive du soluté se fait par l'appui permanent du ressort (14) sur le soufflet (15).In this exploded view, the solute tank 1, provided with a conical cap 5, and an opening for filling (located at the rear of said plug and not shown in the figure), constitutes the bearing surface of a bellows (15), made of folded plastic film (or possibly in the form of a balloon). The gradual release of the solute is done by the permanent support of the spring (14) on the bellows (15).
Entre le ressort (14) et le couvercle (3) du dispositif, on a perçu un film plastique mince (16) dont les extrémités (17) sont revêtus d'un adhésif destiné à coller le dispositif sur la peau.Between the spring (14) and the cover (3) of the device, a thin plastic film (16) was perceived, the ends (17) of which are coated with an adhesive intended to adhere the device to the skin.
En pratique, chaque élément constitutif du dispositif selon l'invention revêt une forme similaire, extra plate et peut être réalisé en matière plastique par moulage par compression, avec utilisation de la technique d'électro-érosion, comme dit ci-dessus, pour les empreintes du bouchon et les rugosités superficielles ou, selon la variante, 1'echancrure. Comme illustré sur les figures 3 et 8, le dispositif est souvent muni de parties adhésives 12 et 17 pour la fixation sur la peau. Mais il peut être utilisé sous d'autres formes comme par exemple sous forme de bracelet ou même de ceinture pour application sur l'abdomen (notamment pour les solutés de trinitrine utilisés comme coronarodilatateurs dans 1•infarctus du myocarde) . On peut bien entendu réaliser le dispositif de l'invention selon diverses dimensions. A titre d'exemple non limitatif, on a expérimenté selon le premier mode de réalisation des figures 1 à 7 avantageusement des dispositifs de diamètre d'environ 40 mm, d'épaisseur 2,8 mm en position de fermeture, avec un diamètre de bouchon de 5 mm environ pour une épaisseur de bouchon de 0,8 mm. Le volume du réservoir était d'environ 1,2 ml. En utilisant la rugosité d'indice 27, correspondant à une distance maximale entre pics et creux de 2,24 !0 microns, l'emmanchement du bouchon dans la cuvette étant particulièrement serré, on a obtenu un débit d'écoulement du soluté médicamenteux d'environ 1,2 ml sur un total de 8 jours. A titre d'exemple confirmé ou mode de réalisation illustré selon la figure 8, on a proposé un dispositif de forme oblongue, de 41 mm sur 46 mm, d'épaisseur 3,2 mm et dont le volume du réservoir était de 1,4 ml.In practice, each constituent element of the device according to the invention takes a similar shape, extra flat and can be made of plastic material by compression molding, using the electro-erosion technique, as said above, for the impressions of the plug and surface roughness or, depending on the variant, the notch. As illustrated in Figures 3 and 8, the device is often provided with adhesive parts 12 and 17 for attachment to the skin. But it can be used in other forms such as for example in the form of a bracelet or even a belt for application to the abdomen (in particular for the trinitrin solutions used as coronarodilators in 1 • myocardial infarction). It is of course possible to produce the device of the invention according to various dimensions. By way of nonlimiting example, experiments have been carried out according to the first embodiment of FIGS. 1 to 7, advantageously devices with a diameter of about 40 mm, a thickness of 2.8 mm in the closed position, with a plug diameter. about 5 mm for a plug thickness of 0.8 mm. The volume of the reservoir was approximately 1.2 ml. Using the roughness of index 27, corresponding to a maximum distance between peaks and valleys of 2.24 ! 0 microns, the fitting of the stopper into the cuvette being particularly tight, a flow rate of the medicated solution was obtained of approximately 1.2 ml over a total of 8 days. As a confirmed example or embodiment illustrated according to FIG. 8, an oblong-shaped device, 41 mm by 46 mm, 3.2 mm thick and whose reservoir volume was 1.4 has been proposed. ml.
Le ressort extra plat (14) s'appliquait avec une force de l'ordre de 0,9 Kg sur le soufflet (15) et donc sur le soluté.The extra-flat spring (14) applied with a force of the order of 0.9 kg on the bellows (15) and therefore on the solute.
Ce dernier s'échappe par le bouchon doseur et diffuseur (5) , pour déboucher sur la surface au contact de la peau. Lors de la mise en place du dispositif sur la peau, on détache 1•opercule de mise en service (18) .The latter escapes through the metering and diffusing cap (5), to lead to the surface in contact with the skin. When the device is placed on the skin, 1 • operculum cover (18) is detached.
Les systèmes selon l'invention sont autorégulables.The systems according to the invention are self-regulating.
En particulier, la surface de la peau qui absorbera le soluté sera d'autant plus petite, que la perméabilité de la peau au principe actif est plus élevée.In particular, the surface of the skin which will absorb the solute will be all the smaller, the higher the permeability of the skin to the active principle.
Du fait la libération mécanique du soluté avec une grande précision, le dosage de ce dernier est extrêmement précis.Due to the mechanical release of the solute with great precision, the dosage of the latter is extremely precise.
Outre les cas d'application susvisés de l'invention, on peut avantageusement signaler encore l'utilisation du dispositif pour l'administration de nicotine ou autres produits dans des cures de désintoxication. In addition to the aforementioned application cases of the invention, it is advantageously possible to also point out the use of the device for the administration of nicotine or other products in detoxification cures.

Claims

REVENDICATIONS
1. Dispositif pour l'administration par voie transcutanée de solutés médicamenteux, caractérisé en ce qu'il comprend : a) un réservoir ou cuvette d'application (1) dont la base est munie d'un orifice de remplissage (4) pour le soluté ainsi que d'une découpe avec bouchon (5) pourvu sur sa périphérie de micro-évidements pour l'administration du soluté sur la peau ; b) un moyen (2) pour pressuriser et régulariser le débit de soluté à l'intérieur du réservoir ; c) un couvercle (3) pour la fermeture étanche dudit réservoir.1. Device for the transcutaneous administration of medicinal solutes, characterized in that it comprises: a) a reservoir or application bowl (1) the base of which is provided with a filling orifice (4) for the solute as well as a cutout with stopper (5) provided on its periphery with micro-recesses for the administration of the solute on the skin; b) means (2) for pressurizing and regulating the flow of solute inside the tank; c) a cover (3) for sealing said tank.
2. Dispositif selon la revendication 1, caractérisé en ce que le moyen de pression est constitué par un ballonnet (2) à base d'un complexe du film de matière plastique rempli d'un mélange de fréons. 2. Device according to claim 1, characterized in that the pressure means is constituted by a balloon (2) based on a complex of the plastic film filled with a mixture of freons.
3. Dispositif selon la revendication 2, caractérisé en ce que le ballonnet (2) est constitué par un film de polyéthylène collé sur un film de polyamide par un adhésif du type polyuréthanne à deux composants.3. Device according to claim 2, characterized in that the balloon (2) consists of a polyethylene film bonded to a polyamide film by an adhesive of the two-component polyurethane type.
4. Dispositif selon l'une quelconque des revendications 2 et 3, caractérisé en ce que le mélange de remplissage du ballonnet comporte approximativement la même quantité de fréon 11 et de fréon 113.4. Device according to any one of claims 2 and 3, characterized in that the filling mixture of the balloon comprises approximately the same amount of freon 11 and freon 113.
5. Dispositif selon la revendication 1, caractérisé en ce que le moyen de pression est constitué p..r une ressort (14) s'appuyant sur un film (15) en matière plastique5. Device according to claim 1, characterized in that the pressure means is constituted by a spring (14) resting on a film (15) of plastic material
6. Dispositif selon la revendication 5, caractérisé en ce que ledit film (15) prend la forme d'un soufflet ou d'un ballonnet qui vient s'appuyer sur la face supérieure du réservoir (1) . 6. Device according to claim 5, characterized in that said film (15) takes the form of a bellows or a balloon which comes to bear on the upper face of the reservoir (1).
7. Dispositif selon l'une quelconque des revendications 1 à 6, caractérisé en ce que le bouchon (5) a une configuration générale conique.7. Device according to any one of claims 1 to 6, characterized in that the plug (5) has a generally conical configuration.
8. Dispositif selon l'une quelconque des revendications 1 à 7, caractérisé en ce que les micro-évidements du bouchon sont constitués par des rugosités (13) de surface obtenues lors du moulage du bouchon (5) par électro-érosion.8. Device according to any one of claims 1 to 7, characterized in that the micro-recesses of the plug consist of roughness (13) of surface obtained during the molding of the plug (5) by EDM.
9. Dispositif selon l'une quelconque des revendications 1 à 7, caractérisé en ce que les micro-évidements sont constitués par une echancrure (6) sur le bord du bouchon.9. Device according to any one of claims 1 to 7, characterized in that the micro-recesses are constituted by a notch (6) on the edge of the plug.
10. Dispositif selon la revendication 9, caractérisé en ce que ladite echancrure (6) sur le bord du bouchon est constituée par une mini-encoche pratiquée parallèlement à l'axe du bouchon et formant un canal annulaire qui se termine, du côté en contact avec la peau, par un évasement de forme triangulaire (7) .10. Device according to claim 9, characterized in that said notch (6) on the edge of the plug is constituted by a mini-notch formed parallel to the axis of the plug and forming an annular channel which ends, on the side in contact with the skin, by a triangular-shaped flare (7).
11. Dispositif selon l'une quelconque des revendications 1 à 10, caractérisé en ce que l'ensemble et chacun des éléments constitutifs ont une forme circulaire, extra-plate, et sont réalisés en matière plastique moulée par injection, ledit bouchon avec son echancrure étant obtenus par la technique d'électro-érosion.11. Device according to any one of claims 1 to 10, characterized in that the assembly and each of the constituent elements have a circular, extra-flat shape, and are made of plastic material injection molded, said plug with its notch being obtained by the electro-erosion technique.
12. Dispositif selon l'une quelconque des revendications 1 à 11, caractérisé en ce qu'il est adapté sur un bracelet ou une ceinture abdominale ou encore utilisé sous forme de pastille avec fixation par pièces adhésives latérales (12) , pour application sur la peau en vue de la délivrance transcutanée du soluté médicamenteux.12. Device according to any one of claims 1 to 11, characterized in that it is adapted to a bracelet or an abdominal belt or also used in the form of a patch with attachment by lateral adhesive pieces (12), for application to the skin for the transcutaneous delivery of the medicated solution.
13. Application du dispositif selon l'une quelconque des revendications 1 à 12 à l'absorption dermique de solutés médicamenteux à base de produits actifs choisis dans le groupe : trinitrine, estradiols, nicotine... lesdits solutés contenant également une petite proportion de mélange de fréon et propanediol-1,2. 13. Application of the device according to any one of claims 1 to 12 to absorption dermal of medicated solutes based on active products chosen from the group: trinitrine, estradiols, nicotine ... the said solutes also containing a small proportion of mixture of freon and 1,2-propanediol.
EP92915288A 1991-07-05 1992-07-01 Device for the dermal absorption of medicinal solutes Ceased EP0679106A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9108483A FR2678514B1 (en) 1991-07-05 1991-07-05 DEVICE FOR THE DERMAL ABSORPTION OF MEDICINAL SOLUTS.
FR9108483 1991-07-05
PCT/FR1992/000617 WO1993000955A1 (en) 1991-07-05 1992-07-01 Device for the dermal absorption of medicinal solutes

Publications (1)

Publication Number Publication Date
EP0679106A1 true EP0679106A1 (en) 1995-11-02

Family

ID=9414782

Family Applications (1)

Application Number Title Priority Date Filing Date
EP92915288A Ceased EP0679106A1 (en) 1991-07-05 1992-07-01 Device for the dermal absorption of medicinal solutes

Country Status (5)

Country Link
US (1) US5558664A (en)
EP (1) EP0679106A1 (en)
CA (1) CA2112898A1 (en)
FR (1) FR2678514B1 (en)
WO (1) WO1993000955A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2678514B1 (en) * 1991-07-05 1993-11-05 Fred Cabrera DEVICE FOR THE DERMAL ABSORPTION OF MEDICINAL SOLUTS.
JPH07227424A (en) * 1994-02-17 1995-08-29 Japan Storage Battery Co Ltd Fluid transporting device
CN108502293A (en) * 2017-02-24 2018-09-07 杨孟君 The packing of the prescription prepared slices of Chinese crude drugs integrates synergy packing box and purposes

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4460368A (en) * 1981-10-29 1984-07-17 Almedco, Inc. Trans-dermal medication system
FR2534140B1 (en) * 1982-10-12 1986-01-31 Fournier Laboratoires NEW DEVICE FOR PERCUTANEOUS ADMINISTRATION OF MEDICINES
IE53703B1 (en) * 1982-12-13 1989-01-18 Elan Corp Plc Drug delivery device
US4619652A (en) * 1982-12-23 1986-10-28 Alza Corporation Dosage form for use in a body mounted pump
US4856188A (en) * 1984-10-12 1989-08-15 Drug Delivery Systems Inc. Method for making disposable and/or replenishable transdermal drug applicators
US5122127A (en) * 1985-05-01 1992-06-16 University Of Utah Apparatus and methods for use in administering medicaments by direct medicament contact to mucosal tissues
US5084008A (en) * 1989-12-22 1992-01-28 Medtronic, Inc. Iontophoresis electrode
US5088978A (en) * 1990-01-26 1992-02-18 Gensia Pharmaceuticals, Inc. Apparatus and method for iontophoretic transfer
US5257987A (en) * 1990-05-21 1993-11-02 Pharmetrix Corporation Controlled release osmotic infusion system
US5087241A (en) * 1990-07-24 1992-02-11 Empi, Inc. Iontophoresis electrode with reservoir and injection site
FR2678514B1 (en) * 1991-07-05 1993-11-05 Fred Cabrera DEVICE FOR THE DERMAL ABSORPTION OF MEDICINAL SOLUTS.
US5273755A (en) * 1991-08-23 1993-12-28 Cygnus Therapeutic Systems Transdermal drug delivery device using a polymer-filled microporous membrane to achieve delayed onset
US5462743A (en) * 1992-10-30 1995-10-31 Medipro Sciences Limited Substance transfer system for topical application

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9300955A1 *

Also Published As

Publication number Publication date
CA2112898A1 (en) 1993-01-21
WO1993000955A1 (en) 1993-01-21
US5558664A (en) 1996-09-24
FR2678514A1 (en) 1993-01-08
FR2678514B1 (en) 1993-11-05

Similar Documents

Publication Publication Date Title
CA2731971C (en) Bottle for packaging liquid that is to be dispensed drop by drop, with antibacterial protection
EP2828002B1 (en) Liquid dispensing device equipped with a removable cap
EP0824469A1 (en) Head and assembly for dispensing a material with a liquid to viscous consistency, comprising a flow reducer
CH694198A5 (en) drug pump having fastening elements for the suture to the outer surface.
FR2858303A1 (en) DEVICE AND METHOD FOR DELIVERING A FLUID
EP0988079B1 (en) Nasal applicator and device for dispensing device comprising same
EP0203633A1 (en) Implantable device for the regular injection of a therapeutic substance
EP2382143A1 (en) Capsule for preparing a beverage, and device
FR2813283A1 (en) INTEGRATED PUMP DISPENSER
EP0576649A1 (en) Device for storing a liquid medicinal substance and dispensing eye drops.
EP2811951B1 (en) Device for packaging and dispensing a substance for ophthalmic use
FR2700316A1 (en) Device for dispensing a medicinal or cosmetic liquid drop by drop contained in a flexible bottle.
CA2353344C (en) Cosmetic or care product application device
EP0906765A1 (en) Nasal inhalation device
CA2880175C (en) Liquid dispensing head, in particular for a bottle for packaging a liquid to be dispensed drop by drop
WO2011048332A1 (en) Distribution head for a device for distributing a fluid product
CA1113818A (en) Device for the administration of medicated substances
EP0679106A1 (en) Device for the dermal absorption of medicinal solutes
EP1513735A1 (en) Flowable composition applying package
EP3069631B1 (en) Improved ball vial
FR2483756A1 (en) ANTISUDORAL LIQUID APPLICATOR CASE AND METHOD FOR DISTRIBUTING SUCH A LIQUID
FR2694492A1 (en) Droplet applicator esp for medicinal liquids used in ophthalmology - has calibrated outlet and piston to expel droplets through it when container is compressed
FR2877923A1 (en) DEVICE FOR SLOWLY DISPENSING A LIQUID, IN PARTICULAR A FRAGRANCE
WO2023135376A1 (en) Eye drop dispensing device
FR2885053A1 (en) Liquid distribution device in a oral cavity, comprises C-shaped flexible silicone hollow reservoir with nipple ends, jaw dental arches, oral floor and adhesive stabilizer laid out on a zone and reservoir to be applied to back face of tooth

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19940105

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU MC NL SE

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

17Q First examination report despatched

Effective date: 19951213

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 19960603