Dispenser for dropwise dispensing of a sterile liquid product containing a surfactant

Abstract

The invention relates to a dispenser, comprising a reservoir (1) including a wall (2) that deforms under pressure and spontaneously returns to its original shape upon release, the reservoir (1) comprising, within an interior space defined by the wall (2), a flexible bag (3) for holding a liquid product. The dispenser comprises air inlet means (14) for admitting air between the wall (2) and the flexible bag (3), a head including a dripping end piece (7) including a dispensing opening, a hydrophilic sterile microporous membrane (10) arranged so that liquid from the flexible bag passes through it on its way to a dispense, and a device configured to keep the membrane (10) wet with the liquid product between two dispenses. The membrane (10) is selectively permeable to the liquid so as to prevent air from re-entering the flexible bag when the dispenser returns to its original shape. The volume of liquid dispensed is compensated by the ingress of a corresponding volume of air between the wall (2) and the flexible bag (3) via the air inlet means (14).

Description

[Technical field]

[0001] The present invention relates to a dispenser for drop-by-drop dispensing of a sterile liquid product containing a surfactant. The dispenser proposed by the present invention has particular advantages for packaging preservative-free liquid ophthalmic products containing a surfactant. [Background technology]

[0002] In many fields of industry, especially in the pharmaceutical, cosmetic and food industries, there are liquid products that must be dripped. These products are used in small doses, one or several drips coming from a dispenser during each use, while it is necessary to maintain the remainder of the product contained in the dispenser for a certain length of time, generally several days or weeks. The products contained in the dispenser must generally be prevented from being contaminated by bacteria etc. coming from outside the dispenser.

[0003] This is especially the case for pharmaceutical compositions, including in particular eye drops, which constitute a preferential application of the present invention. Moreover, it is of particular interest to propose preservative-free ophthalmic solutions, since products used as preservatives in ophthalmic solutions can have significant undesirable effects to ensure the sterility of the ophthalmic product with regard to bacteria and fungi.

[0004] Preservatives, especially benzalkonium chloride, are irritating to the eye, can damage the tear film, and can cause tissue damage through apoptosis. Long-term use of preservatives can have undesirable ocular consequences.

[0005] Therefore, the use of preservative-free ophthalmic products is very often recommended. The first solution to preserve the sterility of such preservative-free ophthalmic products consists of packaging them in single doses, also called "single doses". However, single dose packaging is not applicable to all products, generates a large amount of waste, and the packaging of each dose must be discarded after use. Therefore, when the administration period is long, single dose packaging is not considered appropriate.

[0006] In this context, dispensers containing several doses, or "multi-dose" dispensers, have been developed that are configured to ensure the sterility of the product they contain, including after opening and delivery of the first dose. The purpose of these dispensers is to preserve sterility within the dispenser as long as consumption of the product continues until the contents of the dispenser are completely depleted.

[0007] For example, US Pat. No. 5,999,333 discloses a drip-type dispenser, the reservoir of which includes a deformable wall that allows the creation of an overpressure that causes the contained product to pass through a sterile membrane. The surface of this membrane is partially hydrophilic and partially hydrophobic, more specifically, selectively permeable to aqueous liquids in its hydrophilic portion and selectively permeable to air in its hydrophobic portion. Thus, liquid passes through the membrane in its hydrophilic portion during dispensing before reaching the drop-dispensing end, while air can be sucked into the dispenser through the hydrophobic portion to compensate for the volume of liquid dispensed when the reservoir is no longer compressed and returns to its initial shape. A porous pad allows the regulation of the flow in the dispenser, which is necessary for the proper formation of the drop.

[0008] Dispensers of this type are entirely satisfactory for packaging and dispensing many preservative-free, sterile products, particularly preservative-free liquid ophthalmic products.

[0009] Nevertheless, they are not adapted to dispense some products. In particular, ophthalmic products containing surfactants cannot be dispensed satisfactorily by this type of dispenser. This is because the surfactants interact with the hydrophobic parts of the membrane (obtained by local physicochemical treatment of the hydrophobic membrane) and make them hydrophilic. This prevents the backflow of air into the dispenser, which is necessary to compensate for the amount of liquid dispensed. The result of this is an increase in negative pressure in the dispenser when used, which can cause residual deformation of the dispenser and / or rupture of the membrane.

[0010] Surfactants (or surface active agents or surface agents) are compounds that modify the surface tension between two surfaces. They are compounds that have two parts with different polarities, lipophilic and hydrophilic, respectively. They allow the dissolution of two immiscible phases. Therefore, in the context of ophthalmic products, surfactants are used as solubilizers. The terms surfactant and solubilizer are therefore equivalent in this document.

[0011] Patent document 2 discloses an improved dispenser that reduces the formation of bubbles as well as the retention of air in the porous pad. Nevertheless, although the proposed dispenser substantially improves the quality of dispensing products containing either active ingredients that themselves have surface-active properties, or surfactant additives used as solubilizers, or other excipients such as certain adhesives or lubricants in the family of polyvinyl derivatives or the family of polyethylene glycols, it does not solve the problem of incompatibility of certain surfactants with the hydrophobic portion of the membrane used.

[0012] Patent document 3 discloses a dispenser for preservative-free liquid ophthalmic products, adapted to dispense products containing surfactants. Nevertheless, the proposed dispenser is based on a reservoir with flexible walls, which is deformable by hand as its internal volume gradually decreases towards a rigid neck, i.e. in effect, it is deformable on a reservoir which is deformable in an accordion, the operation of which is not entirely easy for the user.

[0013] Patent document 4 presents a dispenser for ophthalmic products. The reservoir of the dispenser is of the "peel-off" type, which means that the inner layer of the reservoir can separate from the remaining walls to form a deformable inner bag. This dispenser includes a non-return valve through which the product coming out of the dispenser passes, and downstream of this valve, a filter for filtering out certain bacteria can be included. However, this dispenser requires the use of a very effective non-return valve and has a complex configuration if the filtering function is to be performed. [Prior art documents] [Patent documents]

[0014] [Patent Document 1] French Patent Application Publication No. 2816600 [Patent Document 2] French Patent Application Publication No. 2955842 [Patent Document 3] French Patent Application Publication No. 2770495 [Patent Document 4] European Patent Application Publication No. 1985543 Summary of the Invention [Problem to be solved by the invention]

[0015] The present invention aims to propose a dispenser for a sterile liquid product containing at least one surfactant, which solves at least some of the problems mentioned above. The invention thus relates to a dispenser for drop-by-drop dispensing of a sterile liquid product containing a surfactant, comprising a reservoir including a wall defining an internal volume and adapted to deform under the effect of a pressure applied to the reservoir by a user of the dispenser and to spontaneously recover its original shape after the pressure is released. The reservoir further comprises a flexible bag within the internal volume defined by the wall and adapted to contain the sterile liquid product. The dispenser comprises air inlet means between the wall of the reservoir and the flexible bag, and a head attached to the neck of the reservoir and including a dripping end piece including a dispensing opening. The dispenser further comprises a hydrophilic sterile microporous membrane, arranged to pass the liquid coming from the flexible bag in order to deliver the liquid through the dripping end piece. [Means for solving the problem]

[0016] The dispenser includes a device configured to keep the membrane wetted by the liquid product coming from the reservoir between two dispenses of the liquid product. The microporous membrane is selectively permeable to liquid, i.e. it allows the aqueous liquid to pass while opposing the passage of gas when the aqueous liquid is wetted, so that when the dispenser recovers its original shape after dispensing the sterile liquid product, the membrane opposes the backflow of air into the flexible bag of the reservoir, and the volume of the dispensed liquid is compensated by the ingress of a corresponding volume of air between the wall of the reservoir and the flexible bag via the air inlet means.

[0017] The invention therefore proposes a drop-dispensing dispenser perfectly adapted for products containing solubilizing agents (surfactants). The proposed dispenser is simple to use for the user in that it is intuitive in that it allows the product to be dispensed by a simple pressure on the reservoir. Furthermore, the flexible bag present in the internal volume defined by the walls of the reservoir allows the complete dispensing of the product it contains, i.e. it is actually possible to dispense all the doses of the product contained in the flexible bag. The product can also be dispensed while the dispenser is placed in various orientations. This is because, as a dose of the product is dispensed, the volume of the product dispensed is compensated by the ingress of an equal amount of air between the deformable walls of the reservoir and the flexible bag. The volume of the flexible bag is adapted to the volume of the product it contains. The product contained in the flexible bag therefore remains in the immediate vicinity of the dispensing head and no air bubbles are formed in the flexible bag. When the user applies pressure to the deformable wall, the air present between the deformable wall of the reservoir and the flexible bag is prevented from escaping from the space (whether by an automatic air escape prevention means or by the action of the user), so that the flexible bag itself becomes pressurized, causing the expulsion of product through the hydrophilic membrane and the drip end piece.

[0018] The sterile membrane ensures the sterility of the product during its delivery. It also protects the product contained in the reservoir from any contamination coming from outside the dispenser. The dispenser proposed in the present invention also benefits from the property that the sterile membrane is selectively permeable to water (or more generally to aqueous liquids) so that no air returns into the flexible bag after the product has been dispensed. In other words, the membrane, whose filtering capacity ensures the sterility of the product contained in the dispenser, does not allow air to return to the dispenser, thus acting as a backflow prevention device for the dispenser.

[0019] The membrane must be wetted to ensure that there is no passage of air. This is necessarily the case immediately after the product has been dispensed, so that the membrane correctly performs the role of a backflow prevention device, preventing air from being sucked into the flexible bag to compensate for the volume of the dispensed liquid product. Nevertheless, when the product is an ophthalmic product, in order to ensure that the membrane remains wet between two product dispenses, generally spaced only by a few hours, it is proposed to provide a device adapted to ensure that the membrane remains wet. This device can be formed in various ways. A reservoir of liquid can be formed upstream of the membrane, or a very small amount of liquid can be maintained downstream of the membrane.

[0020] Throughout this specification, the terms "upstream" and "downstream" are meant to consider the direction of flow of the liquid product as it is delivered, i.e., from the reservoir, until it emerges from the end piece of the dispenser.

[0021] The dispenser proposed in the present invention can have a simple general configuration, in particular it is not necessary to provide a completely airtight non-return device in addition to the membrane to prevent air from flowing back into the flexible bag of the reservoir when the walls recover their original shape after being deformed by pressure, causing a small drop of product.

[0022] The flexible bag can be formed by peeling off the inner layer of the reservoir. As an alternative to the flexible bag present from the manufacturing in the reservoir of the dispenser, a flexible bag obtained by peeling off the wall of the reservoir is a simple solution, industrially mastered and cheap to obtain the functionality required in the present invention.

[0023] Alternatively, the flexible bag can be a retractable flexible bag that is attached. The use of such a stretchable flexible bag makes it possible in particular to choose a bag with a nominal volume that corresponds exactly to the initial volume of the liquid product to be packaged, while using one and the same deformable wall for various volumes of the product to be packaged.

[0024] The air inlet means can be formed by a hole in the wall of the reservoir adapted to be closed by the user's finger. This is a particularly simple solution to prevent the appearance of air contained between the wall of the reservoir and the flexible bag when the product is dispensed towards the outside of the reservoir, i.e. when pressure is applied to the reservoir. The adapted positioning of the hole in the wall makes the dispenser fully intuitive to use. The hole can therefore advantageously be located between the zones of the reservoir where the user's finger naturally comes to rest when holding the dispenser to dispense the product contained therein. The hole can therefore be located on the side wall of the reservoir, in particular close to the neck of the reservoir, or alternatively on the underside of the reservoir.

[0025] Alternatively, the air inlet means may include a one-way valve configured to allow air to enter between the wall of the reservoir and the flexible bag and to prevent air present between the wall of the reservoir and the flexible bag from exiting towards the outside of the reservoir.

[0026] With this configuration, the emergence of air towards the outside of the reservoir is automatically prevented, which makes the use of the reservoir extremely simple, since there are no specific actions (however simple) to be performed by the user, compared to conventional dispensers with deformable reservoirs.

[0027] The device configured to keep the membrane wet between two dispenses can be a removable cap attached to the dispense head. The cap constitutes a simple and effective way to provide impermeability downstream of the membrane (on the same side as the dripping end piece). Such impermeability prevents the liquid wetting the membrane from moving back towards the flexible bag between two drips.

[0028] The device configured to keep the membrane wet between two instillations can include a valve arranged between the membrane and the dispensing opening of the dripping end piece. It is noted that this valve is not intended to fulfill the function of preventing regeneration of air into the reservoir, which is selectively permeable to water, ensured in the present invention by the hydrophilic membrane. Such a valve simply ensures the maintenance of the liquid product wetting the membrane, especially between two successive dispensations of the product. Thus, simple and inexpensive valves can be used. The valve can be a ball valve, a valve with a deformable thin membrane, etc.

[0029] The dispenser may include a porous pad located between the reservoir and the microporous membrane and arranged for the liquid coming from the flexible bag to pass through it, for the purpose of delivering the liquid through the dripping end piece. The porous pad upstream of the membrane makes it possible to avoid the liquid product coming into contact with the membrane before the first dispensing of the product. Before the first use, the liquid therefore remains completely confined in the reservoir and there is no risk of droplets passing through the membrane and therefore being located in the zone of the end piece, the sterility of which is more difficult to guarantee.

[0030] The porous pad, in conjunction with the microporous membrane, also allows for the creation of a pressure drop as the product passes towards the dispensing orifice, which allows for the regulation of the flow of liquid dispensed by the dispenser In other words, the pad allows the user to more easily dispense the number of drops required by regulating the flow of liquid coming out of the dispenser.

[0031] If a porous pad is placed in contact with the membrane, this can also constitute a device for keeping the membrane wet with the liquid product coming from the reservoir between two dispenses of the liquid product. Nevertheless, this arrangement must be complemented by a means for preventing evaporation of the liquid product, for example a removable cap.

[0032] A satisfactory microporous pad is advantageously manufactured from a material that is inert to the liquid contained in the dispenser. Suitable materials are in particular high porosity felts or foams with open pores, such as can be obtained from various resins of organic polymers. In the main applications of the invention, it is advantageous to manufacture a microporous pad in the form of a felt capsule of polyester or modified polyester resins, in particular low density polyethylene resins or polyethersulfone resins.

[0033] This type or equivalent resin has the advantage in the context of the present invention of providing a cylindrical pad with a diameter of 0.5 to 3 cm and a length between 0.2 and 1 cm, which is flexible enough to fit forcefully and imperviously into the housing of the dispensing head, advantageously a cylindrical housing, and which provides, in the longitudinal direction, the passage of liquid microchannels with an average pore size which may be chosen between 0.3 and 10 microns.

[0034] The microporous membrane can have a pore size of, for example, less than 0.45 μm, preferably less than or equal to 0.22 μm. Such membranes provide so-called sterile filtration, in that they prevent bacteria, fungi and, depending on the selected porosity, certain viruses from passing through. The membrane can be made of various materials, for example of the PES, nylon or PVDF type. This avoids the passage of possible contaminants during the dispensing of the product (usually the product is packaged in a sterile manner, so that contaminants are usually not present there), but also ensures the sterility of the product contained in the reservoir, by preventing the passage of contaminants (bacteria, or even viruses) from outside the dispenser into the reservoir. Therefore, no preservatives are necessary in the product.

[0035] The surface of the dispenser located between the microporous membrane and the dispensing opening may carry a germicidal coating, for example based on silver ions or zinc ions. The microporous membrane may include a germicidal agent, for example based on silver ions or zinc ions.

[0036] The treatment of the surfaces of the dispenser that are downstream of the membrane and tend to come into contact with the product during dispensing or with the product remaining on the drip end piece after dispensing ensures the sterility of the product until it leaves the dispenser. Such treatment generally avoids bacterial growth on the wetted surfaces of the dispenser. The treatment of the surfaces can consist of the application of a coating to these surfaces. Alternatively, the material forming these surfaces can be loaded in its mass with a germicide. Germicides based on metal ions, for example silver or zinc ions, are preferred for the application of the present invention to the packaging of ophthalmic products. The microporous membrane is therefore advantageously placed as close as possible to the dispensing opening of the dispenser.

[0037] The dispenser may contain within its reservoir a preservative-free, sterile, liquid ophthalmic product containing at least one surfactant.

[0038] This is a preferred application of the present invention.The present invention allows the packaging of products in multi-dose formats in simple, inexpensive dispensers that are practical for the user.

[0039] The sterile liquid ophthalmic product may, for example, contain between 0.1% and 5% by volume of a surfactant. At least one surfactant may contain one or more agents selected from the following: Polyethylene glycol 400 (PEG400); Polyoxyethylene sorbitan monooleate (Polysorbate 80); Polyoxyethylene sorbic acid monolaurate (Polysorbate 20); Ethylene oxide, propylene oxide; Methyloxirane polymer; Castor oil PEG-35; Hydrogenated Castor Oil PEG-40; Macrogol cetostearyl ether; Polyoxypropyl glycol 407; Vitamin E (polyethylene glycol succinate); Macrogol Hydroxystearate 15; Caprylocaproyl Macrogol-8 Glycerides; 2-(2-ethoxyethoxy)ethanol; Polyvinylpyrrolidone.

[0040] The liquid ophthalmic product may include at least one additive selected from the group of non-ionic isotonicity agents, antioxidants, buffer systems, lubricating polymers or oligosaccharides. The ophthalmic product may further include a therapeutically effective amount of one or more active agents selected from the group of anti-glaucoma agents, anti-inflammatory agents, immunosuppressants, antiviral agents, antibacterial agents or antifungal agents.

[0041] Other specific features and advantages of the present invention will also become apparent in the following description. [Brief description of the drawings]

[0042] In the accompanying drawings, given by way of non-limiting example, [Figure 1] FIG. 1 shows, in cross-section, a dispenser according to one embodiment of the present invention. [Diagram 2] FIG. 2 shows in cross-section the dispenser of FIG. 1 when the contained product is being delivered. [Diagram 3] FIG. 3 shows, in cross-section, a dispenser according to one embodiment of the invention and illustrates some aspects that may be implemented in such a dispenser. [Figure 4] FIG. 4 illustrates, in cross-section, a dispenser according to another embodiment of the present invention and illustrates some aspects that may be implemented in such a dispenser. [Diagram 5] FIG. 5 shows, in cross-section, a dispenser according to another embodiment of the invention; [Figure 6]FIG. 6 illustrates, in partial cross-section, a dispenser according to yet another embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0043] Figure 1 shows a dispenser according to a first embodiment of the invention. The dispenser comprises a reservoir 1 adapted to contain a liquid product, in particular a sterile liquid product. The reservoir 1 comprises a deformable wall 2 forming the internal volume of the reservoir 1. The wall 2 is configured to be able to deform under pressure exerted by the hand of a user, in particular when the user wants to proceed to deliver one or more drips of the product.

[0044] In the example shown, the wall 2 is a cylindrical peripheral wall. The wall 2 is elastically deformable, i.e. it tends to spontaneously recover its initial shape after pressure is no longer exerted on it.

[0045] The reservoir contains within its internal volume a flexible bag 3. The flexible bag 3 can be an attached bag formed from a flexible plastic material, silicone resin. Alternatively, the flexible bag 3 is formed by peeling of the internal surface of the wall 2, i.e. the flexible bag 3 peels off from the wall 2 during the first delivery of the product. The flexible bag forms a receiving volume 4 in which the liquid product is accommodated. The flexible bag must therefore have sufficient permeability properties to ensure good preservation of the liquid product it contains over an extended period of time, typically weeks or months. In the illustrated example, the flexible bag is kept in contact with the wall 2 of the reservoir at least in the vicinity of the neck 5 of the reservoir.

[0046] The dispenser is fitted with a dispensing head. In the exemplary embodiment shown here, the head for dispensing liquid in droplets comprises an insert 6 arranged inside the neck 5 of the dispenser. An end piece 7 (or nozzle) for dispensing droplets is fixed (or formed) in the insert 6. The insert 6 is fixed tightly and sealingly in the neck 5. The insert 6 can for example be forcefully inserted into the neck 5.

[0047] The insert 6 can be said to be hollow, which is optional in the context of the present invention, in that it provides a space 8 in which a porous pad 9 is received. The porous pad 9 is here cylindrical, adapted to the shape of the space 8. It is manufactured from a hydrophobic material. It can in particular be made of felt with a polyethylene filling. The pad 9 can have an equivalent porosity of, for example, about 100 μm. It has the effect of regulating the flow of the liquid to be dispensed and of preventing the passage of the liquid product from the reservoir 1 to the end piece 7 in the absence of compression of the wall 2 of the dispenser.

[0048] The dispenser also includes a microporous membrane 10. The microporous membrane is said to be sterile or antimicrobial in that it provides filtration fine enough to prevent the passage of all or some of the bacteria, and, where applicable, certain viruses.

[0049] The microporous membrane is located downstream of the porous pad 9 and upstream of the end piece 7. The membrane filters the sterile liquid product contained in the flexible bag 3 of the reservoir 1, thereby protecting it from external contamination, in particular bacterial contamination. It also filters the liquid product contained between each dispense.

[0050] The microporous membrane 10 has a pore size of less than 0.45 μm, preferably less than or equal to 0.22 μm, for example 0.1 μm to 0.2 μm. It is advantageously made from polyethersulfone. The microporous membrane used is hydrophilic (over its entire surface) so as to selectively allow the passage of aqueous liquids. On the other hand, it opposes the passage of gases, especially air. This is especially the case when it is immersed in liquid.

[0051] Thus, the membrane 10 allows aqueous liquid to pass therethrough under the influence of a pressure differential between its two faces, while opposing the passage of air. In particular, so long as the membrane is wetted with liquid, it strongly opposes the passage of air, despite the existence of a pressure differential between the faces of the membrane.

[0052] In the example shown, this membrane 10 is interposed between the end piece 7 and the insert 6. More precisely, the membrane 10 is supported against a base 12 of the dispensing end piece 7. In the form of a disk, it is fixed on its periphery by heat welding between a peripheral ring 11 of this base and a cooperating surface present towards one end of the insert 6.

[0053] Here, the base 12 of the end piece 7 is in the form of a hollow disk which fits onto the insert 6. The base 12 can include, on its internal face (directed towards the internal volume of the reservoir 1), microchannels 13 which facilitate the evacuation of the liquid towards the evacuation opening.

[0054] The dispenser further comprises air inlet means 14. The air inlet means 14 allows air to pass through the wall 2 of the dispenser 1 so as to fit between the wall 2 and the flexible bag 3. In the example shown, the air inlet means 14 is formed by a hole 15, for example a round hole with a diameter of a few millimeters. The hole 15 can be slightly hollowed out in the wall 2.

[0055] Figure 2 shows the dispenser of figure 1 when the product it contains is being delivered. To trigger the delivery of one or more droplets of liquid product, the user presses the dispenser, for example between two fingers 16, thus deforming the wall 2 and reducing its internal volume. When the dispenser is manually compressed, one of the fingers 16 is positioned to block the hole 15, thereby preventing the air present between the wall 2 and the flexible bag 3 from being expelled. The result of this is an increase in pressure in the reservoir, both with respect to the air present between the wall 2 and the flexible bag 3, and with respect to the liquid product, the pressure being transmitted by the flexible bag 3.

[0056] The pressure difference between the internal volume of the reservoir 1 and the surrounding air causes the flow of the liquid product contained within the reservoir through the porous pad 9. The porous pad 9 creates a pressure drop that regulates this flow.

[0057] The liquid then reaches the microporous membrane 10, which in the absence of foam would pass freely through it, and is then passed through the end piece 7, for example via channels 17 having a small cross section, for example capillary channels, allowing the formation of regular droplets 18 in the end piece 7.

[0058] When the user releases the pressure exerted on the reservoir 1, the user's finger 16 seals and closes the hole 15. Air is thus free to enter the space formed between the wall 2 and the flexible bag 3. At the same time, the hydrophilic membrane 10 opposes the return of air into the flexible bag through the end piece 7. As a result, the volume of liquid product expelled is completely compensated by the ingress of a corresponding volume of air into the reservoir 1 between the wall 2 and the flexible bag 3.

[0059] The dispenser thus allows for the delivery of several doses of packaging and preservative-free sterile liquid products, particularly preservative-free ophthalmic products, that contain surfactants that may interfere with the operation of bifunctional hydrophilic / hydrophobic sterile (antimicrobial) membranes.

[0060] Numerous other aspects that can be implemented in such a dispenser are shown in the following figures. In particular, to ensure that there is no suction of air into the flexible bag 3 and more generally in contact with the liquid product upstream of the hydrophilic membrane 10, various means can be used as an alternative to one another or in addition to it. Firstly, a removable cap 19 can be used that closes the end piece 7. The cap 19 can in particular be adapted to be screwed around the neck 5 of the dispenser. Thanks to this method of fastening to the neck 5 of the dispenser and / or thanks to auxiliary means, the cap provides impermeability to air. In particular, a cylinder 20 that accommodates the end piece 7 can be formed in the cap 19, and also a stud 21 that closes the channel 17. Thus, when the dispenser is closed, no ingress of air can occur via the dispensing end piece 7 between two product dispenses.

[0061] In the embodiment of Figure 3, the porous pad 9 is further sized to be in contact with or in close proximity to the membrane 10. In this way, the pad forms a reservoir of liquid that persists in wetting the membrane between two dispenses of product, thus enhancing its selective properties, i.e., it prevents the passage of gas while allowing the passage of liquid. This significantly limits the possibility of air penetrating under and upstream of the membrane.

[0062] Figure 4 shows another embodiment of the invention in which, in addition to the use of a cap 19, it is ensured that the membrane remains wet between two dispenses of product by keeping a very small amount of liquid downstream of the membrane. This can be achieved by providing the dispenser with a valve 22, for example in the immediate vicinity of the end of the end piece 7. The valve shown in Figure 4 is a ball valve, but obviously any other valve technology could be suitable, provided that the valve allows, in particular in addition to the capillary action present in the channel 17, to allow sustained wetting of the membrane 10 by the liquid located immediately downstream of it. It is therefore worth noting that it is not necessarily a case of creating a perfect seal downstream of the membrane, but ensuring that the membrane continues to play its role of preventing backflow of air fulfilling its selective hydrophilicity.

[0063] In the exemplary embodiment shown in figures 1 and 2, the air inlet means 14 are formed by a hole 15 that can be easily blocked by the user. The positioning of the hole 15, which must be natural for the user, can however be adapted according to the dispenser. This position can be at the top of the wall 2, in its centre (in the general extension direction of the dispenser) or at the bottom 23 of the dispenser.

[0064] As illustrated in Figures 3 and 4, the hole 15 can be replaced by a one-way valve 24, allowing air to enter the space between the wall 2 and the flexible bag 3, but preventing it from re-exiting this space. The one-way valve 24 can be a valve with a flexible lip, a ball valve, etc. It can be located on the wall 2, as shown in Figure 4, or on the bottom 23 of the dispenser, as shown in Figure 3. In the embodiment of Figure 3, the one-way valve is included in a hollow 25 formed in the bottom 23 of the dispenser.

[0065] Finally, figure 5 shows an embodiment in which the air inlet means 14 is integrated into the upper part of the dispenser, i.e. in the example shown in its neck 5. A conduit 26 directs the inlet air through the air inlet means towards the space located between the wall 2 and the flexible bag 3. A one-way valve 24 forming the air inlet means 14 is arranged at the mouth of the conduit 26. This embodiment allows a separate integration of the air inlet means, provides a positioning for this means and avoids any risk of unintentional closure during the dispensing of the product contained in the dispenser.

[0066] Instead of a one-way valve, the air inlet means 14 may comprise (in any embodiment of the invention) an element that is permeable to air but adapted to create a significant pressure drop (so that diffusion of air through this element occurs only slowly). To form this element, a thin cover permeable to air, for example made from silicone resin, may be used.

[0067] Thus, when the user presses on the reservoir 1 during product delivery, a high pressure differential is created, but the resistance to the expulsion of product through the end piece 7 is less than the resistance to the passage of air created by the cover, and the time required for dispensing is too short to allow significant passage of air through the cover.

[0068] When the pressure on the reservoir is released, the ingress of air through the end piece 7, which is prevented by the hydrophilic membrane 10, the pressure difference between the internal volume of the reservoir and the outside causes a gradual passage of air through the cover, until the pressure is balanced. Thus, a compensation of the volume of product dispensed by the air between the wall 2 and the flexible bag 3 is achieved.

[0069] Figure 6 presents another embodiment of the invention, where the flexible bag 3 is an attached flexible bag and the air inlet means comprises an element forming a one-way valve 24 at the interface between the flexible bag and an element of the dispenser to which the flexible bag is connected.

[0070] In the example shown, a flexible bag 3 is connected to an insert 6 (although this configuration is also applicable to any embodiment that includes an attached bag).

[0071] The element forming the one-way valve 24 is open and is configured to allow the passage of air when there is no pressure difference between the outside of the dispenser and the internal volume of the reservoir, or to open it as soon as a small negative pressure occurs in the internal volume of the reservoir, whereas as soon as the internal volume becomes overpressurized compared to the pressure outside the dispenser (atmospheric pressure), the element forming the one-way valve 24 closes and prevents air from escaping from the space located between the wall 2 and the flexible bag 3.

[0072] In particular, the element forming the one-way valve 24 may be formed by a thin collar or flat seal which, depending on the pressure difference between the interior and exterior of the dispenser, can be pressed onto the outlet of the conduit 26 connecting the exterior of the dispenser with the internal volume of the reservoir closing the conduit 26, or conversely, can be separated or deformed to leave the conduit 26 transparent. An air-permeable cover as described above can also be used in a variant of this embodiment.

[0073] The embodiment of figure 6 offers the advantages of the embodiment of figure 5 and is simple to implement. In all the embodiments presented below, and more generally in all the embodiments of the invention, it may be advantageous to impart an antimicrobial effect to the surfaces of the dispenser that are located downstream of the membrane 10 and that can be wetted by the liquid product contained in the dispenser. This can be obtained by treatment of these surfaces or of the materials that form these surfaces. Such a treatment, for example based on silver or zinc ions, makes it possible to avoid any bacterial growth on these surfaces. If a small amount of liquid is retained downstream of the membrane 10, the treatment also avoids any bacterial growth in this small amount of liquid.

[0074] The antibacterial treatment therefore concerns in the example shown the end pieces 7, in particular the channels 17 and, where applicable, the inner surfaces of the valves 22. Advantageously, the downstream surface of the membrane 10 is also treated to avoid the occurrence of bacteria.

[0075] It is quite clear that the various aspects presented above with reference to the figures given by way of example can be combined to form other embodiments of the invention. The dispenser thus developed allows the "multi-dose" packaging of preservative-free sterile liquid products. Moreover, the absence of hydrophobic moieties on the hydrophilic membrane allows the "multi-dose" packaging of preservative-free sterile liquid products containing surfactants. Moreover, the dispenser takes advantage of the selective characteristics of the hydrophilic membrane with respect to liquids (which allow it to pass) and gases (whose passage is the opposite) in order to prevent the aspiration of air into the volume receiving the product. Moreover, the volume of the bag adapted to the volume of the liquid product allows the entire product to be dispensed without difficulty, including the last dose present in the dispenser, without residual deformation of the walls of the reservoir.

Claims

1. 1. A dispenser for drop-wise dispensing of a sterile liquid product containing at least one surfactant, comprising: a reservoir (1) defining an internal volume and including a wall (2) adapted to deform under the influence of pressure exerted on the reservoir (1) by a user of the dispenser and to spontaneously recover its original shape after said pressure is released; The reservoir (1) further comprises a flexible bag (3) within the interior volume defined by the wall (2) and adapted to contain a sterile liquid product; an air inlet means (14) between the wall (2) of the reservoir (1) and the flexible bag (3); a head attached to the neck (5) of said reservoir (1), said head comprising a dripping end piece (7) including a dispensing opening, The dispenser further comprises a hydrophilic, sterile, microporous membrane (10) arranged to pass liquid coming from the flexible bag (3) so that the liquid is delivered through the drip end piece (7), said dispenser is characterized in that it comprises a device adapted to keep said microporous membrane (10) wet with the liquid product coming from said reservoir (1) between two dispenses of liquid product, The microporous membrane (10) is selectively permeable to liquids, i.e., when wet, allows aqueous liquids to pass through while opposing the passage of gases, so that when the dispenser regains its original shape after a sterile liquid product has been dispensed, the microporous membrane opposes the backflow of air into the flexible bag (3) of the reservoir (1), and the volume of liquid dispensed is compensated for by the ingress of a corresponding volume of air between the wall (2) of the reservoir (1) and the flexible bag (3) via the air inlet means (14).

2. 2. The dispenser according to claim 1, wherein the flexible bag (3) is formed by peeling off an inner layer of the reservoir (1).

3. 2. The dispenser according to claim 1, wherein the flexible bag (3) is a retractable flexible bag.

4. 4. A dispenser according to any one of claims 1 to 3, wherein the air inlet means (14) is formed by a hole (15) in the wall (2) of the reservoir (1), the hole being adapted to be closed by a finger (16) of the user.

5. 4. A dispenser according to any one of claims 1 to 3, wherein the air inlet means (14) includes a one-way valve (24) configured to allow air to enter between the wall (2) of the reservoir (1) and the flexible bag (3) and to prevent air present between the wall (2) of the reservoir (1) and the flexible bag (3) from escaping towards the outside of the reservoir (1).

6. 4. The dispenser according to claim 1, wherein the device configured to keep the microporous membrane (10) wet between two dispenses is a removable cap (19) attached to the head.

7. A dispenser as claimed in any one of claims 1 to 3, wherein the device configured to keep the microporous membrane (10) wet between two dispenses comprises a valve (22) positioned between the microporous membrane (10) and the dispensing opening of the drip end piece.

8. 4. A dispenser as claimed in any one of claims 1 to 3, wherein the dispenser includes a porous pad positioned between the reservoir and the microporous membrane and arranged to allow liquid coming from the flexible bag to pass through so that the liquid is delivered through the drip end piece.

9. 4. A dispenser according to any one of claims 1 to 3, wherein the microporous membrane has a pore size of less than 0.45 μm.

10. A dispenser as described in claim 9, wherein the microporous membrane has a pore size of 0.22 μm or less.

11. 4. The dispenser of claim 1, wherein the surface of the dispenser located between the microporous membrane and the dispensing opening carries a silver ion or zinc ion based antimicrobial coating.

12. A dispenser according to any one of claims 1 to 3, wherein the microporous membrane (10) contains a disinfectant based on silver ions or zinc ions.

13. 4. The dispenser according to any one of claims 1 to 3, wherein the dispenser contains in the reservoir (1) a preservative-free, sterile liquid ophthalmic product containing at least one surfactant.

14. 14. The dispenser of claim 13, wherein the sterile liquid ophthalmic product comprises between 0.1% and 5% surfactant by volume.

15. 14. The dispenser of claim 13, wherein the at least one surfactant comprises one or more of the following agents: Polyethylene glycol 400 (PEG 400); Polyoxyethylene sorbitan monooleate (Polysorbate 80); Polyoxyethylene sorbic acid monolaurate (polysorbate 20); Ethylene oxide, propylene oxide; Methyloxirane polymer; Castor oil PEG-35; Hydrogenated castor oil PEG-40; Macrogol cetostearyl ether; Polyoxypropyl glycol 407; Vitamin E (Polyethylene Glycol Succinate); Macrogol hydroxystearic acid 15; Caprylocaproyl Macrogol-8 Glycerides; 2-(2-ethoxyethoxy)ethanol; Polyvinylpyrrolidone.

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