WO2006043295A1

WO2006043295A1 - Multidose dispenser for sterile liquid preparations

Info

Publication number: WO2006043295A1
Application number: PCT/IT2005/000170
Authority: WO
Inventors: Federigo Federighi; Mario Federighi
Original assignee: Federigo Federighi; Mario Federighi
Priority date: 2004-10-22
Filing date: 2005-03-25
Publication date: 2006-04-27
Also published as: ITRM20040524A1

Abstract

A dispenser designed for storing liquid products in sterile conditions and for dispensing such products drop by drop, which enables maintaining the sterility of the product even after first opening the bottle, without the need to include preservatives in the liquid product. The dispensed comprises a container body (1) and a dropper assembly (2), which in turn comprises a closure element of the container body (1) ending with an elongated dropper nozzle (5) provided with a central port (6) and a pin plug (7) cooperating with the dropper nozzle (5) to intercept the outflow of a liquid preparation contained in the bottle. The pin plug (7) is placed inside the dropper nozzle (5) in a fixed position with respect to the container body (1), and the dropper nozzle (5) is able to move outward from the pin plug (7) in order to open the port (6) as a result of a mechanical pressure applied to the exterior of the container body (1).

Description

MULTIDOSE DISPENSER FOR STERILE LIQUID PREPARATIONS

DESCRIPTION

The present invention concerns a multidose bottle for dispensing liquid preparations without preservatives. More specifically, the invention con¬ cerns a container specially designed for the sterile conservation of liquid prod¬ ucts and their distribution in the form of drops, the sterility being maintained also after the first opening of the container, without the need to include pre¬ serving agents in the liquid product. Many products, particularly but not exclusively in the medical field, are obtained and used in liquid form, such as solutions or mixtures of one or more liquid components with one or more dissolved solids. For their proper applica¬ tion, these liquids must be dispensed in the form of drops at the time of use. The most common example is that of liquid pharmaceutical products, both for systemic administration (oral drops) and more frequently for topical admini¬ stration, such as on the nasal or oral mucosa, in the auricle of the ear and, above all, in the conjunctival sac. Topical ophthalmic products, such as eye¬ drops and artificial tears, also have the peculiarity that, besides needing to be administered in the form of drops, they must also be applied by the users on their own visual apparatus, and thus normally require the use of droppers with sufficiently elongated nozzles to facilitate as much as possible the actual ap¬ plication of the medication onto the surface of the cornea.

Other examples of liquid products that may require storage in vials or bottles and distribution in the form of drops are particular detergents or addi- tives, also outside the pharmaceutical field, such as in the field of cosmetics or foodstuffs. These fields also have the problem of properly storing liquid prod¬ ucts in sterile conditions and without altering their quality from one use to the next. Particular applications in these fields may also need a drop by drop dispensing of the product which may be as uniform and easily controllable as possible.

The conventional way of preventing or combating the microbial growth in liquid products to be used several times over after the first opening of the relative container consists of adding suitable preserving agents, antioxidants and antibacterial agents in the liquid product itself. The choice and concentra¬ tion of the agents used must in any case be such to guarantee the necessary sterility within the envisaged conditions and expiry date of the product life, and at the same time must not alter the intrinsic characteristics of the liquid prod¬ uct.

More specifically, with reference to products for ophthalmic use that are packaged in multidose bottles of flexible material, the initial sterilization of the product takes place during the bottling phase, after which the bottle is sealed and packaged, and arrives in the consumer's hands in sterile form. When the bottle is first opened, the product is still in a sterile condition, also without the use of preserving agents. On first use, by gently squeezing the bottle some liquid is forced out and made to pass through the dropper nozzle to reach the user. When the gentle pressure exerted on the bottle ceases, the bottle stops distributing the liquid product. However, due to the elasticity of the material used, as soon as the pressure on the bottle ceases, the bottle returns to its original shape and reintegrates the volume of liquid used by sucking in air from the outside environment through its spout. This air is potentially pol¬ luted and could contaminate the remaining liquid in the bottle by starting an oxidative process on the volume of product left inside. This contaminating activity exerted by the outside air is normally prevented by using preservatives or antioxidants: without these, the pharmaceutical product could only be used once because the remaining liquid would become irreparably altered and unusable. All this would be considerably worsened if, during product applica- tion, the dropper came into contact with the user's body, which may potentially be contaminating.

Unless an alternative administration method is used - something which can only be economically justifiable in certain cases - namely the use of single dose packages containing a quantity of product for just one application, which do not require any preservatives, in all other cases the use of preserva¬ tives and antioxidants in multidose bottles containing sterile preparations is made essential in view of a number of features that the product has to main- tain over time, and especially after its container is first opened. These features include the capacity to maintain the liquid in sterile conditions after the bottle is first opened, and also when non-sterile air is sucked back in to replace the liquid used and, in addition, in the case of accidental contact between the dropper and parts of the user's body that may be polluting. Such features also include the capacity to resist oxidation due to contact with the outside air that increasingly replaces the volume of liquid used, and this throughout the useful life of the product once the bottle is first opened.

The addition of preservatives to liquid products for ophthalmic use, although admitted in pharmacology and commonly accepted, is not devoid of a series of drawbacks, however. These include, in particular, the possibility of causing burning sensations or inflammatory or allergic reactions as well as, above all, the proven cytotoxicity of these products. For example, it is well- known that some preservatives used for ophthalmic products have a toxic effect on the goblet cells of the cornea, so that their prolonged use could cause more problems than the ones they can actually help to overcome.

One possible strategy to avoid using preservatives in multidose bot¬ tles of liquid products is to provide one or more antibacterial filters on the liquid pathway towards the exit point in the bottle. In particular, filters with openings or pores of about 0.2 micron in diameter are provided, which me¬ chanically prevent any micro-organisms from getting into the bottle while not preventing the flow of liquid out. An example of this solution is described in the international patent application No. WO 90/05110 (Eye Research Institute of Retina Foundation), where a flexible plastic multidose bottle equipped with a dropper tip containing a pair of filters transversally placed with respect to the liquid flow direction. The filter closest to the bottle body is hydrophilic and has the characteristic of being easily wettable in order to facilitate the outward flow of the liquid product, while the filter located more downstream along the liquid path is of the hydrophobic or water-repellent kind so as not to retain the me- dicinal solution inside it after dispensing it. This results in preventing bacterial growth on the external surface of the filter assembly. It is obvious that, despite the adoption of an antibacterial filter, the external channel of the bottle lying downstream of the filter, including the dropper tip, is still exposed to contami¬ nation by the external environment.

A similar solution envisaging a bottle for liquid products to be dis¬ pensed drop by drop without the use of preservatives and featuring an anti- bacterial filter placed inside the dropper nozzle is disclosed in U.S. patent No. 5,105,993 (La Haye Laboratories), which also describes the presence of an¬ other filter placed on a venting port in the bottle. The said port is intended to allow air to enter the flexible bottle to replace the volume of liquid used.

Still in the specific filed of pharmaceutical products for topical use, U.S. patent No. 5,232,687 (Ursapharm) proposes adopting another, alterna¬ tive or complementary, device in order to guarantee the sterility of a liquid product for topical administration without resorting to preservatives: the use of a solid substance with a germicide action like silver. The device proposed in this connection is not actually a drop dispenser, but a small reciprocating pump that supplies dosed quantities of liquid product in spray form. At each stroke of the pump a pre-fixed quantity of liquid passes into a dispensing chamber and, in order to exit into the outside environment, it must then come into close contact with a silver-based element with germicide functions. The pump device is airtight and does not allow any air to come into the product container to replace the outflowing liquid. This safeguards against any possi¬ bility of contamination from the outside environment. It is evident that such a solution is not very economical, also due to the need to construct a completely airtight device of such solidity to withstand the creation of a depression inside the product container. Moreover, the type of liquid dispensing obtained is not actually in drop form but in jet form, and is not really suitable for applying prod¬ ucts to the eye.

Another commercially available device for supplying liquid phar¬ maceutical products in drop form not requiring the use of preservatives is described in U.S. patent No. 6,336,571 (Laboratoires Thea). In this case the main aim is considered to be that of being able to evenly control the flow of dosed product, with a proper formation of drops. To this end the patent pro¬ poses using a container with flexible bellow-shaped walls, that must necessar- ily be protected by an external rigid shell, that is removable in order to allow access to the bellow-shaped flask containing the liquid. Inside the rigid collar on which the bellow-shaped container is housed there is a pad made of po¬ rous material that creates a head loss sufficient to make the product come out in the form of drops through the dropper nozzle, by manually squeezing the bellow-shaped container. Here too, the necessary aseptic conditions are pro¬ vided by an antibacterial filter placed along the product outflow path down¬ stream of the porous pad but upstream of the dropper nozzle. In this case, too, the inside channel of the dropper nozzle is exposed to bacterial contami- nation from the external environment.

The aforesaid device was considered improvable by the patent- holders themselves, above all as regards construction complexity and produc¬ tion costs, as described in the later U.S. patent application No. 2004/0074925, of the same owner. In this document, the flexible bellow-shaped container and external shell assembly is replaced by a simple flexible single-walled container structured such that outside air can be sucked into the container once liquid outflow has finished, when the flexible container returns to its original shape after being squeezed. In the newly-packaged unused bottle, the entry of out¬ side air is prevented by a frangible internal partition that remains closed until the product is first used. Thereafter, for the remaining period of the product life, the aseptic conditions are guaranteed by an antibacterial filter located along the product outflow path as in the previous version. The document de¬ scribes this filter as being partially hydrophilic, to enable the liquid to pass through during administration, and partially hydrophobic, to enable air to come into the container once liquid outflow ceases.

A further solution for manufacturing multidose dispenser bottles for liquid products without preservatives is described in European patent applica¬ tion EP-A-1319606 (Nihon Tenganyaku Co. and Taisei Kako Co.), which con¬ cerns a double-walled container with an external flexible wall and an internal collapsible one, in which the manually exerted pressure on the external con¬ tainer is transmitted to the internal wall thereby forcing the liquid out during administration. Then, due to a vent hole on the external container, the latter can elastically return to its original shape by sucking air into the gap between the external wall and internal collapsible wall. This air does not come into contact with the product enclosed inside the internal container, thus prevent¬ ing any possible contamination to the product itself. The product flows out of the bottle through a check valve that does not allow the liquid to come back into the internal container. Downstream of this check valve the outflowing liquid still passes through a filter before leaving the container. In this case, too, the device includes a space between the check valve and the dropper tip on which the filter is located, in which some stagnant liquid remains that is not excluded from contact with the outside air, even if the presence of the filter further downstream should at least prevent micro¬ organisms from entering the bottle spout.

In view of the foregoing, it is evident that a device for dispensing products drop by drop, that should do without the addition of preservatives in the product, must be able to prevent the entry of contaminating air inside the dropper nozzle representing the terminal element of the dispenser device. The said element normally ends with a more or less pronounced tip that facilitates product outflow. After use, there is the need to avoid the inside of the dropper being unprotected and wet with the product, which would inevitably mean a contamination of the internal duct of the dropper nozzle itself. Normally, an external cap provides for closure of the bottle. Said cap mechanically closes the tip of the dropper nozzle through suitable protuberances or internal projec¬ tions. However, when this happens (and provided that it happens, since it is not an automatic event), air has already entered the dropper nozzle because, by returning to its original shape, the bottle sucks in outside air to replace the volume of liquid used in the administration.

The known devices envisaging the presence of check valves on the liquid outflow duct still have sections downstream of the check valve - which may particularly include the dropper nozzle - where stagnant liquid remains after administration and where contaminating air can enter from the outside. An object of the present invention is, thus, to provide a stable kind of closing mechanism operating on the dropper nozzle tip, which is operated automati- cally in a safe and continuative manner, without requiring any external action or the use of a potentially contaminating closing device (external cap).

To this end, according to a first aspect of the present invention, there is proposed to create a check valve directly on the bottle dropper nozzle tip. This valve is configured with a truncated cone-shaped pin plug having a shape complementary to that of the nozzle, wherein, however, the valve element with the plugging function is fixed with respect to the bottle body, and the element that functions as the relative housing, i.e. the nozzle, is mobile. Actually, in the lower part of the nozzle tip, where the latter is inserted into the product con- tainer in an airtight and fixed manner, there is a provided an annular mem¬ brane expansion chamber that is sufficiently flexible to allow the dropper noz¬ zle to extend forward with respect to the fixed plug when the pressure on the liquid contained in the bottle is increased by squeezing the bottle itself. The slight advancement of the nozzle with respect to the fixed plug opens up a sufficient gap to enable the liquid to pass through to be dosed in drops from the nozzle tip. As soon as the externally applied pressure ceases, the annular membrane contracts again automatically causing the nozzle to draw back with respect to the fixed pin plug. In this way, as will be made clearer further on, the closure of the dropper after administration is automatic and, above all, it occurs right at the tip of the dropper nozzle, without leaving any liquid residues within the intermediate space inside the dropper.

Therefore, the present invention specifically provides a dispenser for liquid preparations without preservatives, comprising a container body and a dropper assembly, which in turn comprises a container body closure element ending with an elongated dropper nozzle provided with a central port, and a pin plug of a complementary shape to the said dropper nozzle and cooperat¬ ing with it to intercept the outflow of a liquid preparation contained in said dispenser, the pin plug being located inside the dropper nozzle in a fixed posi¬ tion with respect to the container body, and said dropper nozzle being dis- placeabie outward from said pin plug in order to open up the port of the drop¬ per assembly as a result of a mechanical pressure applied to the exterior of the container body. According to a preferred solution, this movement of the dropper noz¬ zle with respect to the fixed pin plug is obtained by the distension of an elastic annular membrane housed in the dropper nozzle and such to establish an expansion annular chamber that dilates due to the pressure exerted on the exterior of the container body. In order to obtain the required elasticity of the membrane while at the same time creating a device that can be manufactured at reasonable cost, said closure element of the container body ending with a dropper nozzle is made up of a suitable polymeric material workable by mold¬ ing, and particularly a polyethylene. As noted, the preferred shape for the dropper nozzle and the corre¬ sponding pin plug according to the present invention is a truncated cone shape, not only because the elongated shape of the dropper facilitates prod¬ uct administration in the eye, if the considered preparation is an ophthalmic product for topical application, but also because closure through the coopera- tion of two truncated cone-shaped coaxial surfaces is the easiest and most reliable form of blockage.

According to some preferred embodiments of the present invention, the container body of the bottle is of the double-wall type with a cavity in be¬ tween, with an elastic external body and an internal collapsible body inside it, that contains the liquid preparation and decreases in volume as the liquid flows out of the diospenser. This type of construction provides the necessary solidity to the bottle, whose external body protects the internal collapsible container, and at the same time allows a gradual transfer of the external man¬ ual pressure applied to the bottle to the internal container, through the air cavity between the two walls. This avoids any excessive dosage dispensing or spraying of the product.

Preferably, the said internal and external bodies of the dispenser are connected rigidly and in airtight manner to the closure element of the con¬ tainer, particularly via the interposition of a ring nut, to the closure device of the container body terminating with the dropper nozzle. Each of said inner and outer container is made of with a polymeric material suitable for the mechani¬ cal characteristics it must have. In particular, the internal container may be made of a thin polyethylene material so that it can collapse as it empties, without sucking in air from the outside. After dispensing the liquid dose, the volume of liquid product leaving the bottle is replaced by a corresponding volume of air sucked in from the outside, but this air fills the cavity between the two walls and does not come into contact with the liquid contained inside the bottle. To enable the air to come into the cavity, the external body of the container has a port that may also be fitted with a suitable valve.

The dispenser according to the present invention is also completed by an external closure capsule which engages the described dropper assembly to create a seal. This closing device preferably consists of a screw cap that can protect the dropper nozzle tip and also a knurled overcap outside the screw cap but connected to it. The combination of screw cap and overcap creates a safety closure system that prevents accidental opening of the bottle, like the kind of devices normally used on pharmaceutical bottles to avoid any improper use by children (child-proof devices). In addition, the capsule envis¬ ages a frangible part only on first opening the bottle - a tamper-evident device also acting as a guarantee seal.

The specific features of the present invention, as well as its advan¬ tages and corresponding operating modalities, will be more evident further on with reference to a specific embodiment of the invention, illustrated merely for exemplary purposes in the attached drawings, wherein:

Figure 1 shows a longitudinal cross-section of a multidose dispenser for liquid preparations according to the present invention, particularly designed for dispensing pharmaceutical products drop by drop without using preserva- tives, and complete with all its closure elements;

Figure 2 shows a longitudinal cross-section of the same bottle of Fig¬ ure 1 , without the external closure capsule;

Figure 3 shows a longitudinal cross-section of the dropper nozzle of the aforesaid bottle; Figure 4 shows a longitudinal cross-section of the corresponding pin plug element for closing the dropper nozzle;

Figure 5 is a perspective view of the said pin plug element shown in Figure 4;

Figure 6 shows a longitudinal cross-section of the ring nut connecting the internal container of the dispenser to the external body, and onto which the dropper nozzle is fixed; Figure 7 is a perspective view of the said ring nut shown in Figure 6;

Figure 8 shows a longitudinal cross-section of the cap that constitutes an element of the bottle closure capsule shown in Figure 1 ;

Figure 9 is a perspective view of the said cap shown in Figure 8;

Figure 10 shows a longitudinal cross-section of the overcap constitut- ing an element of the bottle closure capsule shown in Figure 1 ;

Figure 11 is a perspective view of the said overcap shown in Figure 10; and

Figures 12 a), b), c) and d) schematically show the functioning of the multidose dispenser bottle shown in the above Figures, with a schematic lon- gitudinal cross-section representation of four different operative phases of the bottle.

As shown in Figures 1 and 2, the illustrated embodiment of the dis¬ penser for liquid products according to the present invention is composed of a container body (1) that is closed off at the top with a dropper assembly (2) and completed with an external closure capsule (3). The dropper assembly (2), which is also shown in more detail in Figures 3, 4 and 5, in turn includes a closure element (4), shown specifically in Figure 3, and consists of a single piece of moulded plastic material. This ends with a dropper nozzle (5) of a truncated cone shape, that has a central port (6) for channelling the drops of the liquid contained in the bottle.

The second fundamental element of the dropper assembly (2) is the pin plug (7), which is shown specifically in Figures 4 and 5, and which includes a truncated cone-shaped pin (8) complementary to the dropper nozzle (5), that fits into the latter to completely plug the port (6) of the dropper nozzle (5) with- out any loss of liquid. The opening and closing of this assembly, which creates a check valve for the liquid product dispensed, is obtained by the outward movement of the dropper nozzle (5) with respect to the pin plug (7), which is firmly anchored to the bottle body and is thus fixed. On the other hand, the dropper nozzle (5) is connected to the closure element (4), of which it forms the terminal element, through an elastic annular membrane (9), and can thus slightly move forward (by some tenths of a millimetre, in the case of a dropper bottle for ophthalmic use), as will be shown in detail below, opening up the port (6) for the passage of the product in the form of drops.

Going back to Figures 1 and 2, the container body (1) of the bottle according to the present invention is of the double-wall type with an air cavity in between, and consists of an external elastic cylindrical body (10) and an internal collapsible body (11), also cylindrical but of a smaller diameter, which is the actual container of the liquid product. Both the internal (11) and external (10) bodies are attached to one another by means of a cylindrical ring, specifi¬ cally shown in Figures 6 and 7. After filling up with the liquid product, the con¬ tainer body (1) is then attached - via the ring (12) - to the dropper assembly (2), with the pin plug (7) and closure element (4), in order to obtain the com¬ plete dispenser device shown in Figure 2. All this takes place according to the standard sterilisation procedures.

When closed and in a resting state, the dispenser is as shown sche¬ matically in Figure 12 a): the port (6) of the dropper is closed by the pin (8) of the plug (7). For use as an eye-drop dispenser, the dispenser is held upside- down as shown in Figure 12 b) so that the dropper nozzle (5) points to the user's conjunctival sac, and then the external body (10) of the container (1) is gently squeezed, as shown in Figure 12 c).

This pressure squeezes the flexible external container (10) and is transmitted, via the air cavity, to the internal collapsible container (11). The increased pressure in the internal container (11) then causes a dilation in the expansion chamber formed by the elastic annular membrane (9), and the dropper nozzle (5) moves slightly outward with respect to the pin plug (7), which remains firmly fixed to the container body (1). This opens up a port between the pin (8) and the dropper nozzle (5), which allows the outflow of the drops of product (13). When the user stops squeezing the external body (10), the pressure also ceases in the expansion chamber of the dropper (5) and immediately, due to the elasticity of the material used for the annular mem¬ brane (9), the dropper nozzle (5) withdraws by some tenths of a millimetre and its internal walls come into contact with the internal closing pin (8), thus safely and securely sealing the bottle, as shown in Figure 12 d). It is important to note that the closure of the valve composed of both the dropper nozzle (5) and pin plug (7) occurs exactly at the tip of the dropper nozzle (5), thus avoiding any possible liquid remaining in the nozzle and preventing any contaminating elements from entering the dispenser. Since the internal body (11) of the con¬ tainer (1) is manufactured using thin material and is collapsible, and air is sucked into the cavity between the internal body (11) and external body (10) of the container (1), the internal body (11) remains collapsed and no air comes into contact with the liquid product contained in the dispenser.

To complete the package and insulate the dropper from the external environment, the dispenser according to the present invention is equipped with an external closure capsule (3) (visible in Figure 1) which, in the form illustrated, consists of two superimposed and combining elements. These elements are shown individually in Figures 8-10 and consist of a screw cap (14), whose internal thread (15) engages the thread (16) on the neck of the closure element (4) (see Figure 3), and also an externally knurled overcap (17) which, by fitting over the screw cap (14), creates a secure child-proof closure device. The overcap (17) also includes a collar (18) that is broken and removed on first opening the dispenser and acts as a guarantee seal (tamper- evident device). An unbroken collar demonstrates that the dispenser is still sealed and has not been tampered with. As may be deduced by the aforesaid description, the dispenser ac¬ cording to the present invention can be used in the same way as with other normal dropper bottles for repeated administrations of the product and does not require any specific procedure for its use, but guarantees an immediate and automatic closure of the container when the user stops using the product. This type of stable, safe, sterile and automatic closure occurs at the tip of the dropper nozzle, where the product drops out, and thus guarantees the com¬ plete sterility of the product, its proper storage without any oxidative phenom- ena, and its availability for repeated administrations up to the complete empty¬ ing of the bottle contents.

Moreover, the device is easy to use also by the most inexperienced or elderly users and requires no strange preparatory movements before adminis- tering the liquid product; the dispenser is also easy to open and close.

Finally, the structure of the proposed device is such that it is not ex¬ cessively complex and is easy to produce from a manufacturing standpoint. It also offers the possibility of being tested during production in order to reduce the number of rejects to negligible levels during the product filling phase in sterile conditions.

The present invention has been disclosed with particular reference to some specific embodiments thereof, but it should be understood that modifica¬ tions and changes may be made by the persons skilled in the art without de¬ parting from the scope of the invention as defined in the appended claims.

Claims

1. A dispenser for liquid preparations without preservatives, compris¬ ing a container body (1) and a dropper assembly (2), which in turn comprises a container body closure element (4) ending with an elongated dropper nozzle (5) provided with a central port (6) and a pin plug (7) of a complementary shape to the said dropper nozzle (5) and cooperating with it to intercept the outflow of a liquid preparation contained in said dispenser, the pin plug (7) being located inside the dropper nozzle (5) in a fixed position with respect to the container body (1), and the said dropper nozzle (5) being displaceable outward from said pin plug (7) in order to open up the port (6) of the said dropper assembly (2) as a result of a mechanical pressure applied to the exte¬ rior of the container body (1).

2. A dispenser according to claim 1 , wherein the outward movement of said dropper nozzle (5) with respect to said fixed pin plug (7) is obtained by distension of an elastic annular membrane (9) connected to the dropper noz¬ zle (5) and such to establish an annular expansion chamber that dilates due to a pressure exerted on the exterior of said container body (1).

3. A dispenser according to claims 1 or 2, wherein the said container body closure element (4) ending with a dropper nozzle (5) is made of poly¬ meric material.

4. A dispenser according to any one of claims 1-3, wherein said drop¬ per nozzle (5) and said pin plug (7) are of a truncated cone shape.

5. A dispenser according to any one of claims 1-4, wherein said con- tainer body (1) is a double-walled container with a cavity in between the two walls.

6. A dispenser according to claim 5, wherein said container body (1) comprises an elastic external body (10) and a collapsible internal body (11) enclosed within it, suitable to contain therein the liquid preparation and to decrease in volume as said liquid preparation flows out of the dispenser.

7. A dispenser according to claim 6, wherein both said external body (10) and said internal body (11) of the container body (1) are connected rigidly and in airtight manner to said closure element (4) of the container body (1) ending with said dropper nozzle (5).

8. A dispenser according to claim 7, wherein the connection of said external body (10) and said internal body (11) of the container body (1) to the said closure element (4) is by means of the interposition of a ring nut (12).

9. A dispenser according to any one claims 6-8, wherein said elastic external body (10) and said collapsible internal body (11) of the container (1) are each made of a suitable polymeric material.

10. A dispenser according to any one of claims 5-9, wherein said external body (10) of the container (1) is provided with a port for allowing out¬ side air to enter the cavity between the two walls of the container (1 ).

11. A dispenser according to any one of claims 1-10, also including an external closure capsule (3) that engages the said dropper assembly (2).

12. A dispenser according to claim 11 , wherein said external closure capsule (3) includes a screw cap (14) suitable to protect the said dropper nozzle (5) and also a knurled overcap (17) that fits over the screw cap (14) and is connected to it.

13. A dispenser according to claim 12, wherein the co-operation of said screw cap (14) and said overcap (17) creates a safety closure system preventing children from opening the bottle (child-proof device).