Bottle for the drop-by-drop distribution of a sterile liquid product containing a surfactant

Abstract

The invention relates to a bottle for the drop-by-drop dispensing of a sterile liquid product containing a surfactant. The bottle comprises a reservoir (1) having a wall (2) adapted to deform under pressure exerted on the reservoir by a user of the bottle and to spontaneously return to its original shape after release. The reservoir (1) further comprises a flexible pouch (3) within the internal volume defined by its wall (2) for containing the liquid product. The bottle includes an air inlet means (14) between the wall (2) of the reservoir (1) and the flexible pouch (3); and an attached head comprising a drop-by-drop nozzle (7) having a dispensing orifice.The bottle also includes a hydrophilic, sterilizing, microporous membrane (10) arranged so as to allow the liquid from the flexible bag to pass through it for dispensing. This microporous membrane (10) is selectively permeable to the liquid so as to prevent air from returning to the flexible bag of the reservoir when the bottle returns to its original shape. The volume of liquid dispensed is compensated by the entry 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). See Fig. 1 for abbreviations.

Description

Title of the invention: Bottle for the drop-by-drop dispensing of a sterile liquid product containing a surfactant

[0001] The present invention relates to a bottle for the drop-by-drop dispensing of a sterile liquid product containing a surfactant. The bottle proposed according to the present invention is of particular interest for the packaging of a preservative-free liquid ophthalmic product containing a surfactant.

[0002] There are liquid products that need to be dispensed drop by drop in many areas of industry, particularly in the pharmaceutical field, the cosmetics field, the food industry, etc. These products are used in small doses, one or a few drops from a bottle at each use, while the rest of the product contained in the bottle must be kept for a certain time, generally several days or even several weeks. The product contained in the bottle must generally be kept safe from contamination by bacterial or other agents coming from outside the bottle.

[0003] This is particularly the case for pharmaceutical compositions, including in particular ophthalmic solutions, which constitute the preferred application of the present invention. There is also a particular interest in providing preservative-free ophthalmic solutions. Indeed, the products used as preservatives in ophthalmic solutions, to ensure the sterility of ophthalmic products with respect to bacteria and fungi, can have significant undesirable effects.

[0004] Preservatives, especially benzalkonium chloride, are irritating to the eyes and can alter the tear film, and can cause tissue damage by apoptosis. Long-term use of preservatives has adverse consequences on the eye.

[0005] Thus, the use of ophthalmic products without preservatives is often recommended.

[0006] A first solution for maintaining the sterility of such preservative-free ophthalmic products is to package them in single doses, also called "unidose". However, single-dose packaging is not applicable to all products and generates a lot of waste, as the packaging for each dose must be discarded after use. For long-term treatment, single-dose packaging therefore does not appear appropriate.

[0007] In this context, vials containing several doses, or “multi-dose” vials, configured to ensure the sterility of the product they contain, including after opening and delivery of a first dose, have been developed. These bottles are intended to maintain sterility in the bottle for as long as the product is consumed until the contents of the bottle are completely used up.

[0008] For example, document FR2816600 discloses a drop-type bottle, the reservoir of which comprises a deformable wall making it possible to create an overpressure causing the contained product to pass through a sterilizing membrane. The surface of this membrane is partially hydrophilic and partially hydrophobic, and more particularly selectively permeable to aqueous liquids in its hydrophilic part and selectively permeable to air in its hydrophobic part. Thus, the liquid passes through the membrane in its hydrophilic part during its dispensing before reaching a drop-by-drop dispensing tip, while air can be drawn into the bottle through the hydrophobic part 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 regulation of the flow in the bottle, necessary for the proper formation of the drops.

[0009] This type of bottle is fully satisfactory for packaging and dispensing many sterile products without preservatives, and in particular liquid ophthalmic products without preservatives.

[0010] However, they are not suitable for dispensing certain products. In particular, ophthalmic products containing a surfactant cannot be satisfactorily dispensed by this type of bottle. Indeed, the surfactants interact with the hydrophobic part of the membrane (this being obtained by a localized physicochemical treatment of the hydrophilic membrane) and make it hydrophilic. This prevents the return of air into the bottle, which is necessary to compensate for the quantity of liquid dispensed. This results in an increase in the depression in the bottle as it is used, which can lead to residual deformation of the bottle and / or rupture of the membrane.

[0011] A surfactant (or surface-active agent or surface agent) is a compound that modifies the surface tension between two surfaces. These are compounds that have two parts of different polarity, respectively lipophilic and hydrophilic. They allow two immiscible phases to be solubilized. In the context of ophthalmic products, surfactants are thus used as solubilizing agents. The terms surfactant and solubilizing agent are thus equivalent in this document.

[0012] Document FR2955842 discloses an improved bottle reducing foam formation and air retention in the porous pad. However, if the proposed bottle significantly improves the quality of dispensing a product containing either an active ingredient itself having surfactant properties, or surfactant additives used as solubilizing agents, or other excipients, such as certain viscosifying or lubricating agents from the family of polyvinyl derivatives or that of polyethylene glycols, it does not resolve the problem of the incompatibility of certain surfactants with respect to the hydrophobic part of the membrane used.

[0013] Document FR2770495 discloses a bottle for a preservative-free liquid ophthalmic product which would be suitable for dispensing a product containing a surfactant. However, the proposed bottle is based on a reservoir with a flexible wall, manually deformable by gradually reducing its internal volume towards a rigid neck, that is to say in practice on a deformable accordion-shaped reservoir, the handling of which is not perfectly easy for the user.

[0014] Document EP1985543 presents a bottle for an ophthalmic product. The reservoir of the bottle is of the “delamination” type, which means that the internal layer of the reservoir can separate from the rest of the walls to form a deformable internal pocket. This bottle has a non-return valve through which the product leaving the bottle passes and may have, downstream of this valve, a filter allowing the filtering of certain bacteria. This bottle, however, requires the use of a very effective non-return valve, and has a complex configuration when a filtration function is implemented.

[0015] The invention aims to provide a bottle for a sterile liquid product containing at least one surfactant which solves at least some of the problems mentioned above.

[0016] Thus, the invention relates to a bottle for the drop-by-drop dispensing of a sterile liquid product containing a surfactant, comprising a reservoir comprising a wall defining an internal volume and adapted to deform under the effect of pressure exerted on the reservoir by a user of the bottle and to spontaneously return to its original shape after release of said pressure. The reservoir further comprises a flexible pouch in the internal volume defined by the wall and adapted to contain the sterile liquid product. The bottle comprises an air inlet means between the wall of the reservoir and the flexible pouch, and a head attached to a neck of the reservoir and comprising a drop-by-drop nozzle comprising a dispensing orifice.The bottle further comprises a hydrophilic sterilizing microporous membrane, arranged so as to be crossed by the liquid from the flexible bag for the purpose of delivering said liquid via the drop-by-drop tip, said microporous membrane being selectively permeable to the liquid so as to oppose the return of air into the flexible bag of the reservoir when the bottle returns to its original shape after dispensing the sterile liquid product, the volume of liquid dispensed being compensated by the entry of a corresponding volume of air between the wall of the reservoir and the flexible bag via the air inlet means.

[0017] The present invention thus provides a drop-by-drop dispensing bottle perfectly suited to products containing a solubilizing agent (surfactant). The proposed bottle is simple to use for the user, in that it allows the dispensing product delivery by simply pressing on the reservoir, which is intuitive. In addition, the flexible pouch that is present in the internal volume defined by the reservoir wall allows for complete dispensing of the product it contains, i.e. all doses of product contained in the flexible pouch can be effectively dispensed. Product dispensing can also be carried out while the bottle is positioned in various orientations. Indeed, as doses of product are dispensed, the volume of product dispensed is compensated by the entry of an equivalent volume of air between the deformable wall of the reservoir and the flexible pouch. The volume of the flexible pouch adapts to that of the product it contains. The product contained in the flexible pouch thus remains in the immediate vicinity of the dispensing head, and no air bubbles form in the flexible pouch.When the user applies pressure to the deformable wall, the air present between the deformable wall of the reservoir and the flexible pouch is prevented from escaping from this space (whether by a means which automatically prevents this escaping of air or by an action of the user), so that the flexible pouch itself is put under pressure, causing the expulsion of the product through the hydrophilic membrane and the drip tip.

[0018] The sterilizing membrane guarantees the sterility of the product during its delivery. It also protects the product contained in the reservoir against any contamination coming from outside the bottle. The bottle proposed in the invention further takes advantage of the selectively water-permeable (or more generally aqueous liquid-permeable) nature of the sterilizing membrane to prevent air from returning to the flexible pouch after dispensing the product. In other words, the membrane, whose filtration capacity guarantees the sterility of the product contained in the bottle, does not allow air to return to the bottle and thus serves as a non-return device for the bottle. The bottle proposed in the invention may have a simple general configuration.In particular, it is not necessary to provide a perfectly airtight non-return device in addition to the membrane to prevent air from returning to the flexible pocket of the reservoir when the wall returns to its original shape after being deformed by pressure to cause the dispensing of a few drops of product.

[0019] The flexible pouch can be formed by delamination of an internal layer of the reservoir. As an alternative to a flexible pouch present from the time of manufacture in the reservoir of the bottle, a flexible pouch obtained by delamination of the wall of the reservoir is a simple, industrially mastered, and inexpensive solution for obtaining the function sought in the invention.

[0020] Alternatively, the flexible pouch may be a retractable flexible pouch, which is attached. The use of such a retractable flexible pouch makes it possible in particular to select a pouch having a nominal capacity corresponding precisely to the initial volume of liquid product to be packaged, while using the same deformable wall for different volumes of product to be packaged.

[0021] The air inlet means may be formed by a hole in the wall of the tank adapted to be closed by a finger of the user.

[0022] This is a particularly simple solution for preventing the air contained between the wall of the reservoir and the flexible pouch from escaping when dispensing product to the outside of the reservoir, i.e. when pressure is applied to the reservoir. Adapted positioning of the hole in the wall makes use of the bottle perfectly intuitive. The hole can thus be advantageously positioned in an area of ​​the reservoir where a user's finger naturally rests when holding the bottle in order to dispense product contained in the bottle. The hole can thus be positioned on a side wall of the reservoir, in particular near the neck of the reservoir, or, alternatively, on the bottom of the reservoir.

[0023] Alternatively, the air inlet means may comprise a one-way valve, configured to allow the inlet of air between the wall of the reservoir and the flexible bag and to prevent the air present between the wall of the reservoir and the flexible bag from escaping to the outside of the reservoir.

[0024] According to this configuration, the escape of air towards the outside of the reservoir is automatically prevented, which makes the use of the reservoir extremely simple, since the user does not have to do any particular action (however simple it may be) compared to a conventional bottle with a deformable reservoir.

[0025] The bottle may comprise a device configured to keep the membrane wetted by liquid product from the reservoir between two dispensings of liquid product.

[0026] In order to ensure the total absence of air passage, the membrane must be wetted. This is necessarily the case immediately after dispensing the product, so that the membrane correctly plays its role as a non-return device and prevents air from being sucked into the flexible pouch in compensation for the volume of liquid product dispensed. However, to ensure that the membrane remains wet between two product dispensations, which are generally spaced several hours apart if the product is an ophthalmic product, it is preferable to provide a device adapted to ensure that the membrane remains wet. This device can be constituted in various ways. A liquid reserve can be formed upstream of the membrane, or a very small quantity of liquid can be maintained downstream of the membrane.

[0027] Throughout this document, the terms "upstream" and "downstream" are understood to mean the direction of flow of the liquid product when it is delivered, i.e. from the reservoir to its outlet from the tip of the bottle.

[0028] The device configured to keep the membrane wet between two instillations can be a removable cap, attached to the dispensing head.

[0029] A cap is a simple and effective way of providing a seal downstream (drip tip side) of the membrane. Such a seal prevents the liquid that wets the membrane from returning to the flexible bag between two instillations.

[0030] The device configured to keep the membrane wet between two instillations may comprise a valve positioned between the membrane and the dispensing orifice of the drip tip.

[0031] It is notable that this valve is not intended to ensure the anti-re-aspiration function of air into the tank, which is guaranteed in the invention by the hydrophilic membrane, selectively permeable to water. Such a valve simply ensures the maintenance of the liquid product wetting the membrane at the level of the latter, in particular between two successive dispensings of products. A simple, inexpensive valve can thus be used. The valve can be a ball valve, a valve with deformable blades, etc.

[0032] The bottle may comprise a porous pad located between the reservoir and the microporous membrane and arranged so as to be crossed by the liquid from the flexible pouch for the purpose of delivering said liquid via the drop-by-drop tip.

[0033] The porous pad upstream of the membrane prevents the liquid product from coming into contact with the membrane before the first dispensing of the product. Before the first use, the liquid thus remains perfectly confined in the reservoir, and no drop of liquid risks passing through the membrane and thus ending up in an area, at the tip, where it is more difficult to guarantee its sterility.

[0034] The porous pad also makes it possible to create a pressure drop on the path of the product towards the dispensing orifice, in conjunction with the microporous membrane, which makes it possible to regulate the flow of liquid dispensed by the bottle. In other words, the pad makes it easier for the user to dose the desired number of drops, by regulating the flow of liquid leaving the bottle.

[0035] If the porous pad is positioned in contact with the membrane, it can also constitute a device for keeping the membrane wetted by liquid product from the reservoir between two dispensings of liquid product. This arrangement must nevertheless be supplemented by a means preventing evaporation of the liquid product, for example a removable cap.

[0036] A satisfactory microporous pad is advantageously made of a material that is inert with respect to the liquid contained in the bottle. Suitable materials will be in particular felts or foams with high porosity in open pores such as are known to be obtained from various organic polymer resins. In the main applications of the invention, it is advantageous to produce the microporous pad in the form of a felt pellet of polyester or modified polyester resins, such as in particular low density polyethylene resins or polyethersulfone resins.

[0037] Resins of this type or equivalent have the advantage, within the framework of the invention, of being suitable for providing a cylindrical pad, in diameters of 0.5 to 3 cm and lengths of between 0.2 and 1 cm, which has sufficient flexibility to fit tightly in the advantageously cylindrical body of the dispensing head, and which, in the longitudinal direction, provides the passage of the liquid with microchannels with an average pore diameter which can be chosen between 0.3 and 10 microns.

[0038] The microporous membrane may for example have a pore size of less than 0.45 μm and preferably less than or equal to 0.22 μm.

[0039] Such a membrane provides so-called sterilizing filtration in that it prevents the passage of bacteria, fungi, and, depending on the porosity chosen, certain viruses. The membrane can be made of various materials, for example PES, nylon, PVDF. It prevents the passage of possible contaminants during the dispensing of the product (although normally the product is packaged in a sterile manner, so that no contaminants are normally present), but also guarantees the sterility of the product contained in the reservoir by preventing the passage into the reservoir of contaminants (bacteria, or even viruses) from outside the bottle. No preservative is therefore necessary in the product.

[0040] The surfaces of the bottle located between the microporous membrane and the dispensing orifice may carry a bactericidal coating, for example based on silver ions or zinc ions. The microporous membrane may comprise a bactericidal agent, for example based on silver ions or zinc ions.

[0041] The treatment of the surfaces of the bottle which are downstream of the membrane and which are likely to be in contact with the product during dispensing, or even in contact with product remaining in the dropper tip following dispensing, makes it possible to guarantee the sterility of the product until it leaves the bottle. Such treatment generally prevents any bacterial proliferation on the wet surfaces of the bottle. The treatment of these surfaces may consist of the application of a coating to these surfaces. Alternatively, the material constituting these surfaces may be loaded in its mass with a bactericidal agent. Bactericidal agents based on metal ions, for example silver or zinc ions, are preferred for applications of the invention to the packaging of an ophthalmic product.

[0042] The microporous membrane is thus advantageously located as close as possible to the dispensing orifice of the bottle.

[0043] The bottle may contain in its reservoir a sterile liquid ophthalmic product without preservative and containing at least one surfactant.

[0044] This is the preferred application of the invention. The invention allows a condi supply of such a product in multi-dose form, in a simple, inexpensive bottle, which is practical for the user.

[0045] The sterile liquid ophthalmic product may, for example, contain between 0.1% and 5% by volume of surfactant.

[0046] The at least one surfactant may comprise one or more of the agents chosen from: Polyethylene glycol 400 (PEG 400); Polyoxyethylene sorbitan monooleate (polysorbate 80); Polyoxyethylene sorbitan monolaurate (polysorbate 20); Ethylene oxide, propylene oxide; Methyloxirane polymer; PEG-35 Castor Oil; PEG-40 Hydrogenated Castor Oil; macrogol cetostearyl ether; Polyoxypropyl glycol 407; Vitamin E (polyethylene glycol succinate); Macrogol 15 hydroxy stearate; Caprylocaproyl macrogol-8 glycerides; 2-(2-ethoxyethoxy)ethanol; Polyvinylpyrrolidone.

[0047] The liquid ophthalmic product may comprise at least one additive chosen from the group of non-ionic isotonizing agents, antioxidant agents, buffer systems, lubricating polymers, oligosaccharides. The ophthalmic product may further comprise one or more active agents in a therapeutically effective quantity chosen from the group of anti-glaucomatous agents, anti-inflammatories, immunosuppressants, antivirals, antibacterials or antifungals.

[0048] Other features and advantages of the invention will become apparent in the description below.

[0049] In the attached drawings, given as non-limiting examples: - [Fig.l] represents, in a sectional view, a bottle in accordance with one embodiment of the invention; - [Fig.2] represents, in a sectional view, the bottle of [Fig.l] during delivery of the product it contains; - [Fig. 3] represents, in a sectional view, a bottle in accordance with an embodiment of the invention, illustrating several aspects which can be implemented in such a bottle; - [Fig.4] represents, in a sectional view, a bottle in accordance with another embodiment of the invention, illustrating several aspects which can be implemented in such a bottle; - [Fig.5] represents, in a sectional view, a bottle in accordance with another embodiment of the invention; - [Fig.6] represents, in a partial sectional view, a bottle in accordance with yet another embodiment of the invention.

[0050] [Fig. 1] represents a bottle according to a first embodiment of the invention. The bottle comprises a reservoir 1 adapted to contain a liquid product, in particular a sterile liquid product. The reservoir 1 comprises a deformable wall 2, which forms an internal volume of the reservoir 1. The wall 2 is in particular configured to be able to be deformed under pressure exerted by the hand of a user when the latter wishes to dispense one or more drops of product.

[0051] In the example shown, the wall 2 is a cylindrical peripheral wall. The wall 2 is elastically deformable, that is to say that it tends spontaneously to return to its initial shape after pressure has ceased to be exerted on it.

[0052] The reservoir comprises, in its internal volume, a flexible pouch 3. The flexible pouch 3 may be an attached pouch, formed from a flexible plastic material, silicone, etc. Alternatively, the flexible pouch 3 is formed by delamination of the internal surface of the wall 2, that is to say that the flexible pouch 3 detaches from the wall 2 during the first deliveries of product. The flexible pouch forms a receiving volume 4 in which the liquid product is contained. The flexible pouch must therefore have sufficient permeability characteristics to ensure good preservation of the liquid product that it contains over a long period, typically several weeks or several months. In the example shown, the flexible pouch remains in contact with the wall 2 of the reservoir at least near a neck 5 of the reservoir.

[0053] A dispensing head is attached to the bottle. In the exemplary embodiment shown here, the drop-by-drop liquid dispensing head comprises an insert 6, arranged inside the neck 5 of the bottle. A drop-by-drop dispensing tip 7 (or nozzle) is fixed to (or formed by) the insert 6. The insert 6 is rigidly and tightly fixed in the neck 5. The insert 6 can, for example, be force-fitted into the neck 5.

[0054] The insert 6 is said to be hollow, in that it provides a space 8 in which a porous pad 9 is received, optional in the context of the present invention. The porous pad 9 is here of cylindrical shape matching that of the space 8. It is made of a hydrophobic material. It can in particular be made of a felt with a polyethylene weave. The pad 9 can for example have an equivalent porosity of approximately 100 μm. It has the effect of regulating the flow of liquid dispensed and of preventing the passage of the liquid product from the reservoir 1 towards the end piece 7 in the absence of compression of the wall 2 of the bottle.

[0055] The bottle also comprises a microporous membrane 10. The microporous membrane is said to be sterilizing or antibacterial, in that it provides filtration that is fine enough to prevent the passage of all or part of the bacteria, as well as, where appropriate, certain viruses.

[0056] The microporous membrane is arranged downstream of the porous pad 9 and upstream of the tip 7. The membrane protects by filtration the sterile liquid product contained in the flexible bag 3 of the reservoir 1 from external contamination, in particular by bacteria. It also filters the liquid product contained during each distribution.

[0057] The microporous membrane 10 has a pore size of less than 0.45 μm and preferably less than or equal to 0.22 μm, for example between 0.1 μm and 0.2 μm. It is advantageously formed from polyether sulfone. The microporous membrane used is hydrophilic (over its entire surface) so that it selectively allows the passage of an aqueous liquid. On the other hand, it prevents the passage of gases, in particular air. This is particularly the case when it is soaked with liquid.

[0058] Thus, the membrane 10 allows an aqueous liquid to pass through it under the effect of a pressure differential between its two faces, opposing the passage of air. In particular, as long as the membrane is wetted by the liquid, it strongly opposes the passage of air despite the possible presence of a pressure differential between the faces of the membrane.

[0059] In the example shown, this membrane 10 is interposed between the end piece 7 and the insert 6. More particularly, the membrane 10 is supported against a base 12 of the dispensing end piece 7. In the form of a disc, it is fixed on its periphery by thermal welding between a peripheral crown 11 of this base and a cooperating bearing surface present towards one end of the insert 6.

[0060] Here, the base 12 of the tip 7 has the shape of a hollow disc which fits onto the insert 6. The base 12 may have on its internal face (which is directed towards the internal volume of the reservoir 1) microchannels 13 which facilitate the drainage of the liquid towards the expulsion orifice.

[0061] The bottle further comprises an air inlet means 14. The air inlet means 14 allows air to pass through the wall 2 of the bottle 1, so as to take its place between said wall 2 and the flexible bag 3. In the example shown here, the air inlet means 14 is formed by a hole 15, for example a round hole a few millimeters in diameter. The hole 15 may be formed in a slight recess in the wall 2.

[0062] [Fig. 2] shows the bottle of [Fig. 1] during the dispensing of the product it contains. To cause the dispensing of one or more drops of liquid product, a user presses the bottle for example between two fingers 16, thereby deforming the wall 2, and reducing its internal volume. When manually compressing the bottle, one of the fingers 16 is placed so as to close the hole 15, which prevents the air present between the wall 2 and the flexible bag 3 from escaping. This results in an increase in the pressure in the reservoir, both with regard to the air present between the wall 2 and the flexible bag 3 and for the liquid product, the pressure being transmitted by the flexible bag 3.

[0063] The pressure difference between the internal volume of the reservoir 1 and the ambient air causes a flow of liquid product contained in the reservoir through the porous pad 9. The porous pad 9 creates a pressure drop which regulates this flow.

[0064] The liquid then reaches the microporous membrane 10, which it passes through freely in the absence of foam. The liquid is then evacuated through the tip 7, for example via a channel 17 of small section (for example a capillary channel) formed in the tip 7 and allowing the formation of regular drops 18.

[0065] When the user releases the pressure he exerts on the reservoir 1, his finger 16 ceases to seal the hole 15 in a sealed manner. The air is thus free to enter the space formed between the wall 2 and the flexible pouch 3. At the same time, the hydrophilic membrane 10 opposes the re-aspiration of air into the flexible pouch via the nozzle 7. As a result, the volume of liquid product expelled will be completely compensated by the entry of a corresponding volume of air into the reservoir 1 between the wall 2 and the flexible pouch 3.

[0066] The bottle thus allows the packaging of several doses and the delivery of a sterile liquid product without preservative, in particular an ophthalmic product without preservative, containing a surfactant which could disrupt the functioning of a hydrophilic / hydrophobic bi-functional sterilizing (antibacterial) membrane.

[0067] Many other aspects that can be implemented on such a bottle are illustrated in the following figures.

[0068] In particular, in order to guarantee the absence of air suction into the flexible pouch 3 and more generally in contact with the liquid product upstream of the hydrophilic membrane 10, various means can be used as alternatives or in addition to each other. Firstly, a removable cap 19 for closing the end piece 7 can be used. The cap 19 can in particular be adapted to be screwed around the neck 5 of the bottle. The cap ensures airtightness thanks to its method of attachment to the neck 5 of the bottle, and / or thanks to complementary means. In particular, a receiving cylinder 20 for the end piece 7 can be formed in the cap 19, as well as a pin 21 for closing the channel 17. Thus, once the bottle is closed, between two product dispensings, no air can enter via the dispensing end piece 7.

[0069] In the embodiment of [Fig. 3], the porous pad 9 is further dimensioned to be in contact with or close to the membrane 10. The pad thus constitutes, between two product dispensings, a reserve of liquid which lasts at wet the membrane, thus reinforcing its selectivity properties, namely that it opposes the passage of gases while allowing the passage of liquids. This greatly limits the possibility of air penetrating under the membrane, upstream of it.

[0070] [Fig.4] shows another embodiment of the invention, in which, in addition By using a cap 19, it is ensured that the membrane remains wet between two product dispensings by keeping a very small quantity of liquid downstream of the membrane. This can be achieved by providing the bottle with a valve 22 in the end piece 7, for example in the immediate vicinity of its end. The valve shown in [Fig.4] is a ball valve, but any other valve technology can of course be suitable, provided that the valve allows, in particular in addition to the capillary effect existing in the channel 17, to continue the wetting of the membrane 10 by liquid located immediately downstream of it. It is therefore remarkable that it is not necessarily a question of creating a perfect seal downstream of the membrane, but of ensuring that the membrane continues to play the role of anti-return of air that it ensures by its selectively hydrophilic character.

[0071] In the exemplary embodiment shown in Figures 1 and 2, the air inlet means 14 is formed by a hole 15 that can be easily blocked by the user. The positioning of the hole 15, while it must be natural for the user, can however be adapted according to the bottle. It can be in the upper part of the wall 2, in its middle (in the general direction of extension of the bottle), or even on the bottom 23 of the bottle.

[0072] As illustrated in [Fig. 3] and [Fig. 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 exiting this space. The one-way valve 24 can be a valve with flexible lips, a ball valve, etc. It can be located on the wall 2 as shown in [Fig. 4] or on the bottom 23 of the bottle as shown in [Fig. 3]. In the embodiment of [Fig. 3], the one-way valve is included in a recess 25 formed in the bottom 23 of the bottle.

[0073] [Fig.5] finally presents an embodiment in which the air inlet means 14 is integrated in the upper part of the bottle, namely in the example shown in its neck 5. A conduit 26 makes it possible to guide the air entering 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 discreet integration of the air inlet means and proposes a positioning for this means which avoids any risk of involuntary blockage during the dispensing of the product contained in the bottle.

[0074] Alternatively to a one-way valve, the air inlet means 14 may be equipped (in any embodiment of the invention) with an air-permeable element but adapted to generate a significant pressure drop (so that the diffusion of air through this element can only be done slowly). A thin air-permeable cover, for example made of silicone, can be used to form this element.

[0075] Thus, when the product is dispensed, when the user presses the reservoir 1, a significant pressure differential is created but the resistance against the expulsion of the product through the nozzle 7 is less than the resistance to the passage of air generated by the seal, and the time required for dispensing is too short to allow significant passage of air through the seal.

[0076] When the pressure on the reservoir is released, the entry of air through the nozzle 7 being prevented by the hydrophilic membrane 10, the pressure difference between the interior volume of the reservoir and the exterior causes the progressive passage of air through the seal, until the pressures are balanced. The compensation of the volume of product dispensed by air between the wall 2 and the flexible bag 3 is thus achieved.

[0077] [Fig. 6] shows another embodiment of the invention, in which the flexible bag 3 is an attached flexible bag and the air inlet means comprises a one-way valve element 24 at the interface between the flexible bag and the element of the bottle to which the flexible bag is connected.

[0078] In the example shown here, the flexible pocket 3 is connected to the insert 6 (this configuration being moreover applicable to any embodiment comprising an attached pocket).

[0079] The one-way valve element 24 is open and allows the passage of air in the absence of a pressure difference between the outside of the bottle and the internal volume of the reservoir, or is configured to open as soon as a low vacuum is generated in the internal volume of the reservoir. On the other hand, as soon as the internal volume is in excess pressure compared to the pressure outside the bottle (atmospheric pressure), the one-way valve element 24 closes and prevents air from escaping from the space located between the wall 2 and the flexible bag 3.

[0080] In particular, the one-way valve element 24 may be formed from a thin collar or a flat seal which may either be pressed against the outlet of a conduit 26 connecting the exterior of the bottle and the internal volume of the reservoir, thereby closing the conduit 26, or on the contrary be detached or deformed to release the conduit 26, depending on the pressure differential between the interior and the exterior of the bottle. An air-permeable seal as described above may also be used in a variant of this embodiment.

[0081] The embodiment of [Fig.6] offers the advantages of that of [Fig.5], and is simple to implement.

[0082] In all the embodiments presented below, and more generally in all the embodiments of the invention, there may be an interest in conferring an effect antibacterial to the surfaces of the bottle located downstream of the membrane 10 and likely to be wetted by the liquid product contained in the bottle. This can be achieved by treating these surfaces or by treating the material constituting these surfaces. Such a treatment, based on silver ions or zinc ions for example, makes it possible to prevent any bacterial proliferation on these surfaces. If a small quantity of liquid is retained downstream of the membrane 10, the treatment also prevents any bacterial proliferation in this small quantity of liquid.

[0083] The antibacterial treatment thus concerns, in the examples shown, the internal surfaces of the end piece 7, in particular the channel 17, and where appropriate the valve 22. Advantageously, the downstream surface of the membrane 10 is also treated to prevent any bacterial development.

[0084] Obviously, the different aspects presented above with reference to the figures given as examples can be combined to form other embodiments of the invention.

[0085] The bottle thus developed allows the “multi-dose” packaging of a sterile liquid product without preservative. In addition, the absence of a hydrophobic part on the hydrophilic membrane allows the “multi-dose” packaging of a sterile liquid product without preservative containing a surfactant. In addition, the bottle takes advantage of the selective nature of the hydrophilic membrane with respect to liquids (which it allows to pass) and gases (the passage of which it opposes) to prevent the suction of air into the volume receiving the product. In addition, since the volume of the bag adapts to that of the liquid product, the entire product can be dispensed without difficulty, including the last doses present in the bottle, without residual deformation of the wall of the reservoir.

Claims

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2.

3.

4. Claims Bottle for the drop-by-drop dispensing of a sterile liquid product containing at least one surfactant, comprising a reservoir (1) comprising a wall (2) defining an internal volume and adapted to deform under the effect of pressure exerted on the reservoir (1) by a user of the bottle and to spontaneously return to its original shape after release of said pressure; the reservoir (1) further comprising a flexible pocket (3) in the internal volume defined by the wall (2) and adapted to contain the sterile liquid product; an air inlet means (14) between the wall (2) of the reservoir (1) and the flexible pocket (3); a head attached to a neck (5) of the reservoir (1) and comprising a drop-by-drop tip (7) comprising a dispensing orifice, the bottle further comprising a hydrophilic sterilizing microporous membrane (10), arranged so as to be crossed by the liquid from the flexible bag (3) for the purpose of delivering said liquid via the drop-by-drop tip (7), the bottle being characterized in that it comprises a device configured to keep the membrane (10) wetted by liquid product from the reservoir (1) between two dispensings of liquid product, said microporous membrane (10) being selectively permeable to the liquid, that is to say that it allows the passage of an aqueous liquid while it opposes the passage of gases when it is wet, so that the membrane opposes the return of air into the flexible bag (3) of the reservoir (1) when the bottle returns to its original shape after dispensing the sterile liquid product, the volume of liquid dispensed being compensated by the entry 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), the device configured to keep the membrane (10) wet between two instillations comprising a valve (22) positioned between the membrane (10) and the dispensing orifice of the dropper tip.A bottle according to claim 1, wherein the flexible pouch (3) is formed by delamination of an inner layer of the reservoir (1). Bottle according to claim 1, wherein the flexible pouch (3) is a flexible retractable pouch. Bottle according to one of claims 1 to 3, in which the means air inlet (14) is formed by a hole (15) in the wall (2) of the tank (1) adapted to be closed by a finger (16) of the user.

5. Bottle according to one of claims 1 to 3, in which the air inlet means (14) comprises a one-way valve (24), configured to allow the inlet of air between the wall (2) of the reservoir (1) and the flexible bag (3) and to prevent the exit to the outside of the reservoir (1) of the air present between the wall (2) of the reservoir (1) and the flexible bag (3).

6. Bottle according to one of the preceding claims, in which the device configured to keep the membrane (10) wet between two instillations comprises a removable cap (19), attached to the dispensing head.

7. Bottle according to one of the preceding claims, in which the bottle comprises a porous pad located between the reservoir and the microporous membrane and arranged so as to be crossed by the liquid from the flexible bag for the purpose of delivering said liquid via the drop-by-drop tip.

8. Bottle according to one of the preceding claims, in which the microporous membrane has a pore size of less than 0.45 pm and preferably less than or equal to 0.22 pm.

9. Bottle according to one of the preceding claims, in which the surfaces of the bottle located between the microporous membrane and the dispensing orifice carry a bactericidal coating, for example based on silver ions or zinc ions.

10. Bottle according to one of the preceding claims, in which the microporous membrane (10) comprises a bactericidal agent, for example based on silver ions or zinc ions.

11. Bottle according to one of the preceding claims, said bottle comprising in its reservoir (1) a sterile liquid ophthalmic product without preservative and containing at least one surfactant.

12. The bottle of claim 11, wherein the sterile liquid ophthalmic product comprises between 0.1% and 5% by volume of surfactant.

13. A bottle according to claim 11 or claim 12, wherein the at least one surfactant comprises one or more of the following: Polyethylene glycol 400 (PEG 400); Polyoxyethylene sorbitan monooleate (polysorbate 80); Polyoxyethylene sorbitan monolaurate (polysorbate 20); Ethylene oxide, propylene oxide; Methyloxirane polymer; PEG-35 Castor Oil; PEG-40 Hydrogenated Castor Oil; macrogol cetostearyl ether; Polyoxypropyl glycol 407; Vitamin E (polyethylene glycol succinate); Macrogol 15 hydroxy stearate; Caprylocaproyl macrogol-8 glycerides; 2-(2-ethoxyethoxy)ethanol; Polyvinylpyrrolidone.

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