text:
A nebuliser and a container in each case with an aeration device are proposed, the aeration device being designed for the direct aeration of a liquid space in the container. The container comprises a rigid, gas-tight outer case and a closure, which is opened by connecting or inserting a delivery element. A long storage life and long service life with low loss of fluid or solvent are thereby provided in the form of a simple and inexpensive construction.
1. Nebuliser for a fluid, with an insertable container having a fluid space for the fluid, wherein the container has a rigid, gas-tight outer case and a closure which is openable by connecting or inserting a delivery element of the nebuliser for the withdrawal of fluid from the container, and with an aeration device for aerating the container, wherein the fluid space in the container directly aeratable.
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40. Container for a nebuliser, with a fluid space for a fluid, with a rigid, gas-tight outer case, with a closure and with an aeration device, wherein the closure is openable by connecting up or inserting a delivery element for the withdrawal of fluid from the container, wherein the aeration device is designed for direct aeration of the fluid space.
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1. Field of the Invention
The present invention relates to a nebuliser for a fluid, with a preferably insertable container with a fluid space for the fluid as well as a container for a nebuliser.
2. Description of Related Art
A nebuliser available under the trademark RESPIMAT� in the form of an inhaler is known, and is illustrated in its basic form in International Patent Application Publication WO 91/14468 A1 (U.S. Pat. No. 5,662,271) and in a specific configuration in International Patent Application Publication WO 97/12687 A1 (U.S. Pat. Nos. 6,918,547 and 6,726,124) as well as in
Before the nebuliser is used for the first time, it is opened by loosening a lower housing part, and the sealed container is inserted into the nebuliser. The container is opened by a delivery tube that is introduced into the container as far as the inner bag when the said container is inserted. The lower housing part is then slipped on again.
The drive spring can be tensioned by rotating the lower housing part of the nebuliser. During the tensioning (priming) the container within the nebuliser is moved in a stroke-like manner into the lower housing part and fluid is sucked from the inner bag into a pressure chamber of the pressure generator. After manual actuation of a locking element the fluid in the pressure chamber is pressurized by the drive spring and discharged by means of the delivery tube and without propellant gas through a nozzle into a mouthpiece as an aerosol.
The container comprises an aeration device on the base side, which is pierced during the initial tensioning of the nebuliser and is thereby permanently opened. The aeration device serves to aerate the container so that the inner bag can deflate when fluid is removed, without a reduced pressure thereby being produced in the bag.
International Patent Application Publication WO 00/27543 A1 (U.S. Pat. No. 6,223,933), which forms the starting point of the present invention, discloses various aeration and pressure compensation devices for such a container with a debatable inner bag. The devices serve to provide only a slow pressure compensation between the ambient atmosphere and the gas space between the inner bag and the rigid outer case of the container.
A primary object of the present invention is to provide a nebuliser and a container that is of simple construction and is easy and inexpensive to produce, wherein pressure compensation is possible between the fluid contained in the interior of the rigid container and the surroundings.
The above object is achieved by a nebuliser in accordance with the present invention in which the aeration device is designed for the direct aeration of the fluid space in the container. The fluid space within the meaning of the present invention is the space formed by the container and accommodating the fluid, or a gas space in the container that is in direct contact therewith. In particular, the fluid is filled directly into the outer case of the container or is in contact therewith. A debatable inner bag is not provided. The result is thus a simple and inexpensive construction.
The aeration device is preferably designed in such a way that an excessive evaporation of the fluid, in particular, of a solvent of the fluid, is avoided. For this purpose, the aeration device preferably comprises a channel that, on the one hand, permits rapid pressure compensation, and on the other hand, forms an effective barrier to minimize evaporation. Alternatively or in addition, the aeration device is preferably designed in such a way that it is opened only temporarily, in particular, by or during a movement involving removal of fluid, delivery of fluid, pressure generation and/or atomization.
The solution according to the invention of the invention provides a substantially simpler construction, since a deflatable inner bag is not necessary and is not provided. The aeration device in fact allows direct pressure compensation between the fluid space formed by the rigid container, and the surroundings. Pressure compensation is necessary, in particular, when withdrawing fluid, in temperature changes and/or changes of the ambient pressure. Due to the direct aeration of the fluid space in the container, there is a direct gas connection between the fluid and the surroundings when the aeration device is open, with the result that a quicker pressure compensation is possible. In particular, the aeration takes place via a flow pathway different from that involved in the withdrawal of fluid from the container, in order to be able to prevent, by simple means, entrainment of gas bubbles when fluid is withdrawn.
Further advantages, features, properties and aspects of the present invention are disclosed in the following detailed description of preferred embodiments in conjunction with the accompanying drawings.
In the figures, the same reference numerals are used for identical or similar parts where corresponding or comparable properties and advantages are obtained, even if a relevant description is omitted.
On atomization of the fluid 2, preferably a liquid, in particular, a medicament, an aerosol is formed that can be breathed in or inhaled by a user (not shown). Normally inhalation is performed at least once a day, in particular, several times a day, preferably, at predetermined time intervals, depending on the patient's medical condition.
The known nebuliser 1 comprises an insertable and preferably replaceable container 3 with the fluid 2. The container 3 thus forms a reservoir for the fluid 2 to be atomized. The container 3 preferably contains a sufficient amount of fluid 2 or active substance in order, for example, to be able to provide up to 200 dose units, i.e., to permit, for example, up to 200 atomizations or uses. A typical container 3, as is disclosed in International Patent Application Publication No. WO 96/06011 A2 (U.S. Pat. No. 5,833,088), accommodates a volume of ca. 2 to 10 ml.
The container 3 is substantially cylindrical or like a cartridge, and after the opening of the nebuliser 1, can be inserted into it, and optionally, replaced. The container is of rigid construction, the fluid 2 being accommodated in the container 3 in a fluid space 4 formed by a deflatable bag.
Furthermore, the nebuliser 1 comprises a pressure generator 5 for delivering and atomizing the fluid 2, in particular, in each case, in a predetermined and optionally adjustable dose amount. The pressure generator 5 has a holder 6 for the container 3, an associated and only partly-shown drive spring 7 with a manually actuatable locking element 8 for unlocking purposes, a delivery tube 9 with a non-return valve 10, a pressure chamber 11 and a delivery nozzle 12 in the region of a mouthpiece 13. The container 3 is fixed via the holder 6, in particular, in a notched manner, in the nebuliser 1, so that the delivery tube 9 dips into the container 3. In this connection, the holder 6 may be designed so that the container 3 can be released and exchanged.
When the drive spring 7 is axially tensioned, the holder 6 together with the container 3 and the delivery tube 9 shown in the drawings is moved downwards and fluid 2 is suctioned from the container 3 through the non-return valve 10 into the pressure chamber 11 of the pressure generator 5.
During the subsequent release of tension after actuating the locking element 8, the fluid 2 in the pressure chamber 11 is pressurized, wherein the delivery tube 9 together with its now closed non-return valve 10 is moved upwardly again due to release of tension on the drive spring 7, and now serves as a plunger. This pressure forces the fluid 2 through the discharge nozzle 12, whereby it is atomized to form an aerosol 14, as illustrated in
A user or patient (not shown) can inhale the aerosol 14, whereby air can be sucked into the mouthpiece 13 through at least one air feed opening 15.
The nebuliser 1 comprises an upper housing part 16 and an inner part 17 rotatable relative thereto (
The housing part 18 may be rotated relative to the upper housing part 16, whereby it engages the lower part 17 b of the inner part 17, as shown in the drawing. In this way, the drive spring 7 is tensioned in the axial direction via a gear mechanism (not shown) acting on the holder 6. As a result of the tensioning, the container 3 is moved axially downwards until the container 3 adopts an end position illustrated in
The design, construction and mode of operation of several embodiments of the proposed nebuliser 1 and container 3 are describe in more detail hereinafter, reference being made to further figures, though only essential differences compared to the nebuliser 1 and container 3 according to
The container 3 comprises a rigid, gas-tight outer case 23. The term �gas-tight� is understood in the context of the present invention to mean that a diffusion of the fluid 2 or at least of an essential constituent of the fluid 2, such as a solvent, for example, water or ethanol, is not possible or is prevented. Therefore, the outer case 23 is, in this respect, at least substantially impermeable. Furthermore, the term �gas-tight� is basically understood to mean that air or other gas cannot penetrate through the outer case 23 for the purposes of pressure compensation.
Preferably, the outer case 23 is made of glass, metal or another suitable, gas-tight plastics, such as COC (cyclopolyolefin polymer) in order to achieve the desired hermeticity. In addition or alternatively, the outer case 23 can also be fabricated from a composite material, for example, with an inner lamination of plastics, inner coating, or the like.
The container 3 does not have a deflatable bag or the like. Instead, the fluid 2 is filled directly into the outer case 23 and is in contact therewith. The outer case 23 forms the fluid space 4 for the fluid 2, the said space consequently being rigid.
Preferably the container 3 is fabricated as a single-walled structure, i.e., without a bag, inner case or the like. The outer case 23 is, preferably, formed as a single layer, though it may also be fabricated from several layers, if necessary.
The container 3 comprises a closure 24 that seals the container 3 in a gas-tight manner, preferably after the latter has been filled with the fluid 2. The closure 24 is preferably mounted on the front or top of the container 3 or on its outer case 23.
The seal 24 preferably comprises an outer cover or seal 25 and a cap or insert 26 arranged thereunder. In order to achieve the desired hermeticity, which is essential for a long storage life, particularly when the container 3 is sealed, the cover or seal 25, which made, in particular, of a metal foil, is formed so as to be gas tight. Preferably, the insert 26 is inserted into the container 3 together with the metal film and is hot-sealed, in order to achieve the desired hermeticity. In addition or alternatively, the insert 26, and optionally the seal 25, may be secured and fastened by crimping a metal ring or the like on the top of the container.
According to a modified embodiment (not shown), the cover or seal 25 may also be formed by a protective cap or the like that is welded on, bonded on or secured in another suitable way.
Preferably the seal 25 forms an original closure of the container 3.
Furthermore, the container 3 comprises a sealing element 27 arranged in the interior, such as a septum, a membrane or the like, shown only partly in the figures. The sealing element 27 is preferably formed by the closure 24 or insert 26 and serves in particular, to radially seal an inserted delivery element, in particular, the delivery tube 9 or the like, which is not shown in
In order to extract fluid 2 the container 3 is inserted into the nebuliser 1, and in particular, is opened by connecting or introducing the delivery element, i.e., in this case, the delivery tube 9. In particular, the delivery tube 9 pierces the seal 25 and is introduced into the sealing element 27 or is possibly even forced through the latter, in order to produce a fluid connection to the fluid 2 in the container 3. The introduction of the delivery tube 9 thus, preferably, leads to an opening of the container 3, in particular, of the seal 25 and of the closure 24. However, the opening may alternatively also take place independently of the removal of fluid and/or independently of the delivery element, in particular, by means of a separate part or the like (not shown).
According to the invention, an aeration device 28 is provided for the preferably direct aeration of the fluid space 4 in the container 3. Thus, the aeration device 28, preferably, forms a direct gas connection between the fluid 2 and the surroundings when the aeration device 28 is open, in order to allow the pressure compensation already mentioned in the introduction.
In the first embodiment the aeration device 28 is integrated into the closure 24 or at least forms a part thereof and/or is arranged thereon. However, the aeration device 28 may, in principle, also be arranged and/or formed on the nebuliser 1, in particular, separately from the container 3 as is also explained hereinafter with the aid of other embodiments.
In the first embodiment, the aeration device 28 includes a flow channel or throttle channel, which hereinafter is briefly denoted as channel 29 and can be seen more clearly in the enlargement of the insert 26 according to
The channel 29 is configured so that it produces a relatively low flow resistance with regard to a rapid pressure compensation�in particular, in the case of rapid successive withdrawal of fluid 2 from the container 3. However, the channel 29 forms a barrier to the evaporation or diffusion of the fluid 2, in particular, of constituents of the fluid 2 such as a solvent, for example, water or ethanol, that is relatively difficult to overcome. The evaporation or diffusion and the escape of fluid 2 or constituents such as solvents or the like�hereinafter also referred to in brief as �fluid evaporation��depends significantly on the resistance to diffusion through the opened aeration device 28�and therefore, in the first embodiment, depends on the channel 29. On account of its length, the channel 29 produces a relatively large diffusion resistance if it has a sufficiently small hydraulic diameter.
Preferably, the channel 29 has a mean or hydraulic diameter of 0.01 mm to 1 mm. The length of the channel 29 is preferably between 10 times and 1000 times the channel diameter and/or is basically 5 to 50 mm, particularly, preferably, about 10 to 25 mm.
The channel 29 is preferably formed by or on the closure 24. In particular, the channel 29 joins the interior or fluid space 4 of the container 3 to a space 30 in the insertion region of the closure 24 for the delivery element or delivery tube 9, and specifically, preferably, between the sealing element 27 and the cover or seal 25. This connection has the advantage that the aeration device 28 and the channel 29 has no connection with the surroundings when the container 3 is closed�i.e., when the cover or seal 25 is intact�and therefore is likewise closed. Only when the cover and seal 25 are opened, in particular, by piercing or introducing the delivery tube 9, are the connection of the space 30 to the surroundings, and thus the aeration device 28, opened.
In the first embodiment the aeration device 28 is designed for permanent aeration of the fluid space 4 in the container 3 when the closure 24 is opened or pierced for the first time and/or after withdrawal of fluid 2 for the first time. In particular, the aeration device 28 is opened by connecting or introducing the delivery element or delivery tube 9. A piercing element 22, in particular, a separate piercing on the base, is therefore not necessary for the aeration. This simplifies the construction.
The container 3 and the aeration device 28 are preferably opened exclusively by mechanical action or manual actuation. This results in a simple and functionally reliable construction.
With the nebuliser 1 according to the invention, the container 3, the delivery element or delivery tube 9 and/or the associated holder 6 for the container 3 are, preferably, movable in a stroke-like manner during the fluid withdrawal, fluid delivery, pressure generation and/or atomization. The opening and piercing of the container 3 by the delivery tube 9 and the insertion of the delivery tube 9 into the container 3 is preferably produced by this movement and during the initial tensioning of the drive spring 7. Accordingly, in the first embodiment, the opening of the aeration device 28 is preferably produced by the aforementioned movement.
Instead of the aeration device 28 being permanently open, it may also be opened only temporarily, in particular, only during the aforementioned movement. This is also explained in more detail hereinafter with the aid of other preferred embodiments.
The channel 29 preferably runs at least over a section between the cap and insert 26 of the closure 24, on the one hand, and the cover and seal 25, on the other hand. This simplifies manufacture since the channel 29 is formed as an open groove in the insert or cap 26 and can then be covered by the seal 25. In particular, the channel 29 surrounds the delivery tube 9 and/or an insertion opening and/or the space 30 for the delivery tube 9, in an annular or spiral manner, at least over a section 31. Alternatively or in addition, the channel 29 may also run in a meandering or zigzag fashion.
When the delivery tube 9 is inserted, a radial gap or annular space exists between the open end of the radial section 33 of the channel 29 and the cylindrical surface of the delivery tube 9, so that the aeration through the channel 29 is not hindered by the delivery tube 9 when the seal 25 is opened. However, the seal 25 may, if necessary, also be configured in such a way�in particular, in the manner of a membrane or the like�and/or may co-operate hermetically with the delivery tube 9, that the free exchange of gas between the space 30 and the surroundings is restricted or prevented, in order to minimize the undesirable vaporization of fluid.
As has already been explained, the aeration device 28 for the direct aeration of the fluid space 4 is formed in the container 3. When the aeration device 28 is open, a direct exchange of gas is possible between the gas space in direct contract with the fluid 2 and the surroundings of the container 3. In order to prevent an escape of fluid 2 through the aeration device 28, the aeration device 28, preferably, comprises at least one semi-permeable element 34 that is impermeable to liquids but permeable to gases. The semi-permeable element 34 thus prevents a possible outflow of the fluid 2 through the aeration device 28.
As is illustrated in
The aeration device 28 is configured in such a way as to permit a relatively rapid pressure compensation. This is necessary for example, in the case of rapid successive withdrawal of fluid 2 from the container 3. In particular, the aeration device 28 is configured in such a way that a pressure compensation of at least 20 hPa takes place with a half-life time of at most 60 sec, in particular, 30 sec or less. In the first embodiment this is achieved by suitably dimensioning the channel 29 and the other possible flow resistances, for example, through the semi-permeable element 34.
In the first embodiment, the insert or cap 26 adjoins a dip tube 35, which, for example, is slipped on, and preferably, extends at least substantially as far as the container base 21 in the interior of the container 3. The dip tube 35 is formed, for example, by a flexible silicone tube.
To open the container 3, the delivery tube 9 is inserted into the container 3, whereby the seal 25 is opened and an at least substantially tight connection is formed between the delivery tube 9 and the sealing element 27 of the closure 24.
Further embodiments according to the invention are explained hereinafter with reference to the further figures, though only essential differences compared to the first embodiment and compared to the known implementation of nebuliser 1 and container 3 illustrated in
The float 36 always floats on the surface of the fluid 2 in the container 3. Accordingly, the second embodiment permits a de-aeration independently of the position/orientation of the container 3. Furthermore, the use of the float 36 permits a possibly easier, namely position-independent, aeration since, in any arbitrary position of the container 3, no fluid 2 can prevent the direct gas connection between the gas space in the container 3 and the channel 29, with the result that only the pressure of the relevant fluid 2 has to be overcome in the aeration.
The aeration element 38 is preferably formed as a line made of glass or another suitable material. The aeration element 38 comprises at least one, preferably a plurality of aeration openings 39, with each of which is associated a semi-permeable element 34 (not shown), in order, on the one hand, to permit an aeration and/or de-aeration, and on the other hand, to prevent an entry of fluid 2 into the aeration element 38 and an outflow of fluid 2 from the container 3 through the aeration device 28. Alternatively or in addition, the semi-permeable element 34 or material may also be arranged in the aeration element 38.
Preferably, the aeration openings 39 are provided in the region of the head and its closure 24 of the container 3, as well as in the region of the container base 21. In addition, a plurality of aeration openings 39 are preferably formed in the region of the container base 21 on a lateral section 40 of the aeration element 38 extending at least substantially in a radial plane. A very good aeration and/or de-aeration is thereby effected, independently of the position of the container 3.
A particular advantage of the fourth embodiment is that, with a plurality of parallel channels 29, a possible blockage of one channel 29 does not lead to a failure of the aeration. A particularly high functional reliability is thus ensured. Apart from this, the previous explanations, in particular, as regards the third embodiment, apply correspondingly to the fourth embodiment.
In the fifth embodiment, the channel 29 basically comprises only a radial section 33, as indicated in
The inner container 41 is designed having at least one aeration opening 39, preferably a plurality of aeration openings 39, to the intermediate space 42 which, in turn, are covered or closed by associated semi-permeable elements 34, as indicated in
In the fifth embodiment, the dip tube 35 is preferably formed by a flexible silicone tube or the like which, in particular, is attached to the insert 26 or its sealing element 27 or is connected thereto in some other way.
Alternatively or in addition to the channel 29, the aeration device 28 may, in all embodiments, include a valve (not shown) for opening and closing the aeration device 28. In particular, the valve, and thus the aeration device 28, is opened only temporarily, and therefore, in contrast to the previously-described embodiments, not permanently when the container 3 is open.
If necessary, the valve may be opened only when a certain pressure difference is exceeded and/or only temporarily during the aforementioned movement, i.e., in particular, during the stroke-like movement involved in fluid withdrawal, fluid delivery, pressure generation and/or atomization of the container 3, delivery element 9 and/or associated holder 6.
The valve (not shown) is preferably integrated into the closure 24. Alternatively or in addition, the valve may, however also be arranged separately from the closure 24 on the container 3, for example, on the base or at the side on the cylindrical surface, or separately from the container 3 on the nebuliser 1.
According to a further variant (not shown), the aeration device 28 may also be formed by an automatically closing membrane, an automatically closing septum, or the like. In this case too, the aeration device 28 may again, if necessary, be arranged on or in the closure 24 or separately therefrom, in particular, on the base or on the circumstantial surface of the container 3.
According to a further variant (not shown), the aeration device 28 may also comprise an, in particular, radial, preferably closable, aeration opening 39 arranged on the outer case 23 of the container 3, for aerating and de-aerating the fluid space 4 of the container 3.
In the previous embodiments, the aeration device 28 was arranged and formed exclusively on the container 3. In the sixth embodiment, the aeration device 28 is arranged or formed at least partly or completely on the nebuliser 1, and in particular, therefore, not on the container 3.
The aeration device 28 in the sixth embodiment includes a bypass on the delivery element or delivery tube 9, which is formed on the outside, in particular, by a preferably oblong or screw-shaped flute 43, groove, flat section or the like. Thus, the bypass also runs axially, in order to form, in particular, a connection between the insertion region or space 30 of the closure 24 and the interior of the container 3 when the aeration device 28 is open. To this end, the channel 29 is also provided in the region of the sealing element 27, which preferably runs radially and forms the connection between the bypass within the sealing element 27 and the interior of the container 3.
Preferably, the bypass�in particular, as regards its axial position and length�and the axial arrangement of the channel 29 as well as the axial position and length of the sealing element 27 are matched to one another in such a way that, with a relative movement of the delivery tube 9 towards the container 3 and the sealing element 27, the aeration device 28, i.e., the gas connection between the interior of the container 3 and the surroundings, is only temporarily opened. In the sixth embodiment, the delivery tube 9 is, for this purpose, axially moveable or displaceable relative to the container 3 during the tensioning of the nebuliser 1 for the withdrawal of fluid and during the release of the tensioning, i.e., during the pressure generation and atomization of the fluid 2. In this connection, the container 3 can, for example, be held rigidly, i.e., not axially displaceably, in the housing part 18. However, it is conversely also possible for the delivery tube 9 to be fixed in the nebuliser 1 and for the container 3 to move preferably in a stroke-like manner during the tensioning and detensioning procedure.
On account of the aforementioned preferred relative movement of the delivery tube 9 in the container 3, the delivery tube 9 adopts, relative to the sealing element, two different end positions in the primed nebuliser 1�i.e., after withdrawal of fluid�and in the deprimed nebuliser 1�i.e. after the atomization stroke. Preferably, in the sixth embodiment, a closure of the aeration device 28 takes place in at least one of the two end positions, preferably in both end positions. In the illustrated example, this is achieved by virtue of the fact that, in the two end positions, a section of the delivery tube 9, arranged as desired either axially above or below the bypass, co-operates with the sealing element 27�in particular, with the part of the sealing element 27 arranged axially above the channel 29 in
During the tensioning procedure for the withdrawal of fluid, the part of the delivery tube 9 arranged axially underneath the bypass and the part of the sealing element 27 arranged axially underneath the channel 29, as shown in
According to a variant (not shown), the semi-permeable element 34 or corresponding semi-permeable material is arranged in the bypass, i.e., in particular, the flute 43, groove, flat section or the like is filled therewith so that only the passage of gas is permitted, but an outflow of fluid 2 through the bypass is prevented.
In the sixth embodiment, the bypass is arranged on the outside on the delivery tube 9. However, in principle, the bypass may be arranged on another part or at another site. In particular, the bypass may also be arranged internally in the delivery tube 9. This is discussed hereinafter with the aid of the seventh embodiment and further embodiments.
Particularly preferably, the delivery tube 9 comprises an inner tube 45 and an outer tube 46, which are arranged concentrically with respect to one another. The inner tube 45 forms the delivery channel 44 in the interior. The annular space between the inner tube 45 and the outer tube 46 forms the aeration channel 29.
The two tubes 45, 46 are securely joined to one another, preferably by welding, for example, in the region of their ends. However the two tubes 45, 46 may also be joined to one another in another suitable way, for example, by adhesion, soldering, deforming or the like.
The multipart design of the delivery tube 9�either from the two tubes 45, 46, as explained hereinbefore, or from even more parts�may, if necessary, also be employed independently of the aeration and aeration device 28, in particular, in a nebuliser 1 of the type mentioned in the introduction or in another nebuliser 1. In particular, in this connection, the aeration channel 29 in the delivery tube 9 may be omitted or sealed. The multipart design allows, in particular, an inexpensive and/or dimensionally accurate production of the delivery tube 9.
In the seventh embodiment, the delivery tube 9 is securely joined to the holder 6. In particular, the delivery tube 9 or its outer tube 46 is, for this purpose, provided with a holding region 47 having a corrugated outer contour or the like. The delivery tube 9 is injection molded together with the holding region 47 into the holder 6. Thus, the holder 6, preferably, engages the holding region 47 in a positive interlocking manner. The delivery tube 9 is thus axially fixed in the holder 6 in a positive interlocking manner.
The delivery tube 9, in the illustrated example, preferably, comprises radial aeration openings 39 in the outer tube 46, in order to produce a gas connection to the channel 29. Preferably, at least one inner aeration opening 39 (in the diagram according to
The inner aeration opening 39 is situated in an aeration region 48 that is arranged, with respect to the sealing element 27, axially within the container 3 and is formed by the closure 24 and its insert 26 or by the adjoining dip tube 35, in particular, by means of a V-shaped or funnel-shaped widening or the like. The aeration region 48 is in contact with the interior of the container 3 in particular, with a gas space above the fluid 2 (not shown in
In order to prevent fluid 2 penetrating into the aeration region 48 and through the inner aeration opening 39 into the channel 29, the aeration space 48 is preferably sealed by the semi-permeable element 34 with respect to the interior of the container 3 and thus against the fluid 2. In the illustrated example, at least one semi-permeable element 34 is arranged between the insert 26 and the dip tube 35. Furthermore, the delivery tube 9 with its free end, optionally, only with its inner tube 45 projecting axially relative to the outer tube 46, seals the aeration region 48 by bearing against or engagement in the dip tube 35. However, other structural solutions are also possible in this case.
Alternatively or in addition, the semi-permeable element 34 or material may also be arranged directly in the delivery tube 9 or channel 29.
In particular, however, the arrangement of the inner aeration opening 39 underneath the sealing element 27 is not absolutely necessary. For example, this arrangement may also be provided in the region of the space 30 or in the region of sealing element 27, as in the sixth embodiment.
From what has been said hereinbefore, it follows that, in the seventh embodiment, in contrast to the sixth embodiment, the delivery tube 9 is not moved relative to the container 3 or closure 24 for withdrawal of fluid, in particular, during the tensioning and untensioning of the nebuliser 1.
Depending on the dimensioning of the channel 29 formed in the delivery tube 9 and the relevant requirements, the aeration device 28 according to the seventh embodiment may, after the piercing and opening of the container 3, i.e., after insertion of the delivery tube 9, remain permanently open or may be opened only temporarily, in particular, only during the withdrawal of fluid or if a certain pressure difference is exceeded.
A seal 49 of the aeration device 28, which is associated with the outer end of the channel 29 and with the outer (surrounding atmosphere side) aeration opening 39 of the channel 29, is shown very diagrammatically in
Various structural solutions are possible for the opening and closure of the aeration device 28, i.e., for the temporary closure, in particular, of the outer aeration opening(s) 39. Individual structural solutions are explained hereinafter with the aid of further embodiments and with reference to FIGS. 12 to 23.
The actuating element 52 is held in a resilient manner by the associated spring element 50 in the position covering the aeration openings 39. When the nebuliser 1 is primed, the actuating element 52 is displaced axially against the spring force of the spring element 50, whereby the aeration openings 39 are at least temporarily freed and opened. In the rest state�also in the primed state�the aeration openings 39 are closed again on account of the restoring force of the spring element 50. In the ninth embodiment, preferably, corresponding to the eighth embodiment, there takes place simply a temporary opening of the aeration device 28, exclusively during the tensioning procedure and during the withdrawal of fluid.
In the illustrated closed state the actuating part 52 is axially pretensioned by the associated spring element 50 with respect to the counter-seal 55, so that the seal 49 is pressed axially tightly against the counter-seal 55. A closed sealing space is thus formed around the aeration opening(s) 39. The seal 49 may optionally comprise an annular, elastic flange or the like to provide a bearing surface for or connection to the delivery tube 9 for the radial sealing with respect to the said delivery tube 9.
The opening of the aeration device 28 and of the sealing space for the release of the outer aeration openings 39 takes place when the nebuliser 1 is primed corresponding to the ninth embodiment. During tensioning, the actuating part 52 is displaced axially against the force of the spring element 50 and the seal 49 is thereby retracted axially from the counter-seal 55. In the primed state, the spring element 50 then effects a re-closure. Thus, in the eleventh embodiment, an only temporary opening of the aeration device 28 again takes place, namely preferably, exclusively during the withdrawal of fluid.
The actuating arm 51 can be elastically radially deflected and has a free end projecting axially beyond the seal 49. When the aeration device 28 is closed, the seal 49 seals off the aeration opening 39, in particular, by radially bearing against it, in which the seal 49 either covers and seals the associated aeration opening 39 directly, or does so only indirectly by bearing against a non-rigid intermediate part 59, illustrated in
Furthermore, the aeration device 28 includes the actuating part 52, which, in the thirteenth embodiment, comprises a bearing curve 60 for the actuating arm 51.
Consequently, in the thirteenth embodiment, preferably, also only a temporary opening is envisaged, in particular, only during the tensioning procedure and withdrawal of fluid. However, other opening times and/or durations are also feasible and a permanent opening of the aeration device 28�in particular, by a suitably altered bearing curve 60�can be realized.
It is obvious that other structural solutions for the temporary release of the outer aeration openings 39 and of the channel 29 are also possible. In particular, other valves or the like may also be used for this purpose.
Preferably, the connecting element 61 is adequately sealed with respect to the closure 24, for example, corresponding to the delivery tube 9, in order to minimise the losses of fluid by diffusion, evaporation or the like.
According to a variant (not shown), the connecting element 61 and the channel 29 for aeration and de-aeration may also be formed separately from the holder 6 by another part of the nebuliser 1 and/or may engage independently of the closure 24 on the container 3, in particular, if necessary, on the base side. The container base 21 is then preferably provided with a corresponding suitable base element or the like.
The possibly only temporary opening of the aeration device 28 may�as already explained on the basis of the various embodiments�take place through and/or during a movement of the delivery element, in particular, delivery tube 9, relative to the container 3. Alternatively or in addition, this may also involve a movement of the holder 6 and/or of the inner part 17 relative to the container 3, or may involve a movement of the container 3 relative to another part of the nebuliser 1. The movement may, in particular, serve for fluid removal, fluid delivery, pressure generation and/or atomization. In particular, the movement may be a translational and/or rotational and/or superimposed and/or stroke-like movement. The movement may, as already mentioned, lead to an initial opening of the container 3 or closure 24 and/or to an initial or temporary opening of the aeration device 28.
According to a further variant (not shown), the nebuliser 1 and container 3 may, in addition to the aeration device 28, which is designed for a rapid pressure compensation, also comprise a pressure compensation device (not shown) for a slow pressure compensation, in particular, when the aeration device 28 is closed, and/or for pressure compensation in the case of changes in temperature or ambient pressure. The pressure compensation device may, optionally, also be designed as a valve that preferably opens when a specific pressure difference is exceeded.
In general it should be mentioned that with the nebuliser 1 according to the invention the container 3 can preferably be inserted, i.e., can be incorporated into the nebuliser 1. Consequently, the container 3 is, preferably, a separate structural part. However, the container 3 may, in principle, also be formed directly by the nebuliser 1 or by a structural part of the nebuliser 1, or may be integrated in some other way into the nebuliser 1.
The container 3 is, preferably, sterile or sterilisable. Particularly preferably, the closed container 3 is designed to be suitably temperature-resistant. In addition, the closure 24 maintains the container 3, preferably, sterile.
As already mentioned, individual features, aspects and/or principles of the aforedescribed embodiments may also be arbitrarily combined with one another and in particular, in the known nebuliser according to
In contrast to fixed equipment or the like, the nebuliser 1 according to the invention is, preferably, designed to be transportable, and in particular, is a mobile hand-held device.
The solution according to the invention may, however, be employed not only in the individual nebulisers 1 described herein, but also in other nebulisers or inhalers, for example, powder inhalers or so-called �metered dose inhalers�.
Particularly preferably, the nebuliser 1 is designed as an inhaler, in particular, for medical aerosol treatment. Alternatively, the nebuliser 1 may, however, also be designed for other purposes, preferably, for the atomization of a cosmetic fluid, and may, in particular, be designed as a perfume or fragrance atomizer. The container 3 accordingly contains, for example, a medicament formulation or a cosmetic liquid, such as perfume or the like.
Preferably, the fluid 2 is a liquid, as already mentioned, in particular, an aqueous or ethanolic medicament formulation. However, it may also be another medicament formulation, a suspension or the like, or also a particulate composition or powder.
Preferred constituents and/or formulations of the preferably medicinal fluid are listed hereinafter. As already mentioned, these may be aqueous or non-aqueous solutions, mixtures, ethanol-containing or solvent-free formulations or the like. The fluid 2, particularly preferably, contains the following:
All inhalable compounds, for example, also inhalable macromolecules, as disclosed in EP 1 003 478, are used as pharmaceutically active substances, substance formulations or substance mixtures. Preferably, substances, substance formulations or substance mixtures that are used for inhalation purposes are employed to treat respiratory pathway conditions.
Particularly preferred in this connection are medicaments that are selected from the group consisting of anticholinergic agents, betamimetics, steroids, phosphodiesterase IV inhibitors, LTD4 antagonists and EGFR kinase inhibitors, antiallergic agents, ergot alkaloid derivatives, triptanes, CGRP antagonists, phosphodiesterase V inhibitors, as well as combinations of such active substances, e.g. betamimetics plus anticholinergic agents or betamimetics plus antiallergic agents. In the case of combinations at least one of the active constituents contains preferably chemically bound water. Anticholinergic agent-containing active substances are preferably used, as single preparations or in the form of combination preparations.
The following, in particular, may be mentioned as examples of effective constituents or their salts:
Anticholinergic agents are preferably selected from the group consisting of tiotropium bromide, oxitropium bromide, flutropium bromide, ipratropium bromide, glycopyrronium salts, trospium chloride, tolterodine, tropenol 2,2-diphenylpropionate methobromide, scopine 2,2-diphenylpropionate methobromide, scopine 2-fluoro-2,2-diphenylacetate methobromide, tropenol 2-fluoro-2,2-diphenylacetate methobromide, tropenol 3,3′,4,4′-tetrafluorobenzilate methobromide, scopine 3,3′,4,4′-tetrafluorobenzilate methobromide, tropenol 4,4′-difluorobenzilate methobromide, scopine 4,4′-difluorobenzilate methobromide, tropenol 3,3′-difluorobenzilate methobromide, scopine 3,3′-difluorobenzilate methobromide, tropenol 9-hydroxy-fluorene-9-carboxylate methobromide, tropenol 9-fluoro-fluorene-9-carboxylate methobromide, scopine 9-hydroxy-fluorene-9-carboxylate methobromide, scopine 9-fluoro-fluorene-9-carboxylate methobromide, tropenol 9-methyl-fluorene-9-carboxylate methobromide, scopine 9-methyl-fluorene-9-carboxylate methobromide, cyclopropyltropine benzilate methobromide, cyclopropyltropine 2,2-diphenylpropionate methobromide, cyclopropyltropine 9-hydroxy-xanthene-9-carboxylate methobromide, cyclopropyltropine 9-methyl-fluorene-9-carboxylate methobromide, cyclopropyltropine 9-methyl-xanthene-9-carboxylate methobromide, cyclopropyltropine 9-hydroxy-fluorene-9-carboxylate methobromide, cyclopropyltropine methyl 4,4′-difluorobenzilate methobromide, tropenol 9-hydroxy-xanthene-9-carboxylate methobromide, scopine 9-hydroxy-xanthene-9-carboxylate methobromide, tropenol 9-methyl-xanthene-9-carboxylate methobromide, scopine 9-methyl-xanthene-9-carboxylate methobromide, tropenol 9-ethyl-xanthene-9-carboxylate methobromide, tropenol 9-difluoromethyl-xanthene-9-carboxylate methobromide and scopine 9-hydroxymethyl-xanthene-9-carboxylate methobromide, optionally in the form of their racemates, enantiomers or diastereomers, and optionally in the form of their solvates and/or hydrates.
Betamimetics which may be used are preferably selected from among albuterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, indacaterol, isoetharine, isoprenaline, levosalbutamol, mabuterol, meluadrine, metaproterenol, orciprenaline, pirbuterol, procaterol, reproterol, rimiterol, ritodrine, salmeterol, salmefamol, soterenot, sulphonterol, tiaramide, terbutaline, tolubuterol, CHF-1035, HOKU-81, KUL-1248, 3-(4-{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-hexyloxy}-butyl)-benzolsulphonamide, 5-[2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one, 4-hydroxy-7-[2-{[2-{[3-(2-phenylethoxy)propyl]-sulphonyl}ethyl]-amino}ethyl]-2(3H)-benzothiazolone, 1-(2-fluoro-4-hydroxy-phenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol, 1-[3-(4-methoxybenzyl-amino)-4-hydroxyphenyl]-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-N,N-dimethylaminophenyl)-2-methyl-2-propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1.4-benzoxazin-8-yl]-2-[3-(4-methoxyphenyl)-2-methyl-2-propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1.4-benzoxazin-8-yl]-2-[3-(4-n-butyloxyphenyl)-2-methyl-2-propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1.4-benzoxazin-8-yl]-2-{4-[3-(4-methoxyphenyl)-1.2.4-triazol-3-yl]-2-methyl-2-butylamino}ethanol, 5-hydroxy-8-(1-hydroxy-2-isopropylaminobutyl)-2H-1.4-benzoxazin-3-(4H)-one, 1-(4-amino-3-chloro-5-trifluormethylphenyl)-2-tert.-butylamino)ethanol and 1-(4-ethoxycarbonyl-amino-3-cyano-5-fluorophenyl)-2-(tert.-butylamino)ethanol, optionally in the form of the racemates, enantiomers or diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and/or hydrates thereof.
Steroids which may be used are preferably selected from among prednisolone, prednisone, butixocortpropionate, RPR-106541, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, ST-126, dexamethasone, (S)-fluoromethyl 6a,9a-difluoro-17a-[(2-furanylcarbonyl)oxy]-11b-hydroxy-16a-methyl-3-oxo-androsta-1,4-diene-17b-carbothionate, (S)-(2-oxo-tetrahydro-furan-3S-yl) 6a,9a-difluoro-11b-hydroxy-16a-methyl-3-oxo-17a-propionyloxy-androsta-1,4-diene-17b-carbothionate and etiprednol-dichloroacetate (BNP-166), optionally in the form of the racemates, enantiomers or diastereomers thereof, and optionally, in the form of the salts and derivatives thereof, the solvates and/or hydrates thereof.
PDE IV-inhibitors which may be used are preferably selected from among enprofyllin, theophyllin, roflumilast, ariflo (cilomilast), CP-325,366, BY343, D-4396 (Sch-351591), AWD-12-281 (GW-842470), N-(3,5-dichloro-1-oxo-pyridin-4-yl)-4-difluoromethoxy-3-cyclopropylmethoxybenzamide, NCS-613, pumafentine, (−)p-[(4aR*,10bS*)-9-ethoxy-1,2,3,4,4a,10b-hexahydro-8-methoxy-2-methylbenzo[s][1,6]naphthyridin-6-yl]-N,N-diisopropylbenzamide, (R)-(+)-1-(4-bromobenzyl)-4-[(3-cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone, 3-(cyclopentyloxy-4-methoxyphenyl)-1-(4-N′-[N-2-cyano-S-methyl-isothioureido]benzyl)-2-pyrrolidone, cis[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane-1-carboxylic acid], 2-carbomethoxy-4-cyano-4-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)cyclohexan-1-one, cis[4-cyano-4-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)cyclohexan-1-ol], (R)-(+)-ethyl[4-(3-cyclopentyloxy-4-methoxyphenyl)pyrrolidin-2-ylidene]acetate, (S)-(−)-ethyl[4-(3-cyclopentyloxy-4-methoxyphenyl)pyrrolidin-2-ylidene]acetate, CDP840, Bay-198004, D-4418, PD-168787, T-440, T-2585, arofyllin, atizoram, V-11294A, Cl-1018, CDC-801, CDC-3052, D-22888, YM-58997, Z-15370, 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-thienyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine and 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(tert-butyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridin, optionally in the form of the racemates, enantiomers or diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and/or hydrates thereof.
LTD4-antagonists which may be used are preferably selected from among montelukast, 1-(((R)-(3-(2-(6,7-difluoro-2-quinolinyl)ethenyl)phenyl)-3-(2-(2-hydroxy-2-propyl)phenyl)thio)methylcyclopropane-acetic acid, 1-(((1(R)-3 (3-(2-(2,3-dichlorothieno[3,2-b]pyridin-5-yl)-(E)-ethenyl)phenyl)-3-(2-(1-hydroxy-1-methyl-ethyl)phenyl)propyl)thio)methyl)cyclopropane-acetic acid, pranlukast, zafirlukast, [2-[[2-(4-tert-butyl-2-thiazolyl)-5-benzofuranyl]oxymethyl]phenyl]acetic acid, MCC-847 (ZD-3523), MN-001, MEN-91507 (LM-1507), VUF-5078, VUF-K-8707 and L-733321, optionally in the form of the racemates, enantiomers or diastereomers thereof optionally in the form of the pharmacologically acceptable acid addition salts thereof and optionally in the form of the salts and derivatives thereof, the solvates and/or hydrates thereof.
EGFR-kinase inhibitors which may be used are preferably selected from among cetuximab, trastuzumab, ABX-EGF, Mab ICR-62, 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-cyclopropylmethoxy-quinazoline, 4-[(R)-(1-phenyl-ethyl)amino]-6-{[4-(morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-cyclopentyloxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{[4-((R)-6-methyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[2-((S)-6-methyl-2-oxo-morpholin-4-yl)-ethoxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline, 4-[(R)-(1-phenyl-ethyl)amino]-6-({4-[N-(tetrahydropyran-4-yl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopentyloxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-[(R)-(tetrahydrofuran-2-yl)methoxy]-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6,7-bis-(2-methoxy-ethoxy)-quinazoline, 4-[(R)-(1-phenyl-ethyl)amino-6-(4-hydroxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine, 3-cyano-4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-ethoxy-quinoline, 4-[(R)-(1-phenyl-ethyl)amino]-6-{4-((R)-6-methyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-[(tetrahydrofuran-2-yl)methoxy]-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-{[4-(5,5-dimethyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{2-[4-(2-oxo-morpholin-4-yl)-piperidin-1-yl]-ethoxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-amino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-methanesulphonylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-3-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(piperidin-3-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[1-(2-acetylamino-ethyl)-piperidin-4-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)-amino]-6-(tetrahydropyran-4-yloxy)-7-ethoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{trans-4-[(morpholin-4-yl)carbonylamino]-cyclohexan-1-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(piperidin-1-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(cis-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-ethansulphonylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-(2-methoxy-ethoxy)-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-(2-methoxy-ethoxy)-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(tetrahydropyran-4-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(cis-4-{N-[(piperidin-1-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{cis-4-[(morpholin-4-yl)carbonylamino]-cyclohexan-1-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[2-(2-oxopyrrolidin-1-yl)ethyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(1-acetyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(1-methyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methyl-piperidin-4-yloxy)-7(2-methoxy-ethoxy)-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(N-methyl-N-2-methoxyethyl-amino)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-ethyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-N-methanesulphonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-acetyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-methylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[trans-4-(N-methanesulphonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-trans-4-dimethylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[2-(2,2-dimethyl-6-oxo-morpholin-4-yl)-ethoxy]-7-[(S)-(tetrahydrofuran-2-yl)-methoxy]-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-cyano-piperidin-4-yloxy)-7-methoxy-quinazoline, and 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(2-methoxyethyl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, optionally in the form of the racemates, enantiomers or diastereomers thereof, optionally in the form of the pharmacologically acceptable acid addition salts thereof, the solvates and/or hydrates thereof.
By acid addition salts, salts with pharmacologically acceptable acids which the compounds may possibly be capable of forming are meant, for example, salts selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrobenzoate, hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-tolenesulphonate, preferably hydrochloride, hydrobromide, hydrosulphate, hydrophosphate, hydrofumarate and hydromethanesulphonate.
Examples of antiallergics are: disodium cromoglycate, nedocromil.
Examples of derivatives of the ergot alkaloids are: dihydroergotamine, ergotamine.
For inhalation, it is possible to use medicaments, medicament formulations and mixtures including the abovementioned active constituents, as well as their salts, esters and combinations of these active constituents, salts and esters.
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Barthes, RolandLine breaks: Ro¦land Barthes
Pronunciation: /bɑːt , baʀt/
Definition of Barthes, Roland in English:
( 1915–80), French writer and critic. Barthes was a leading exponent of structuralism and semiology in literary criticism, while later works were influential in the development of deconstruction and post-structuralism.
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greater than others in power or influence

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Oct 23 -
Lexington - Transportation
CDL-A Truck Drivers - Local Runs
CDL-A Drivers for dedicated local runs out of London, KY. needed.
$700 - $1000 per week
Now offering: $500 Sign-on bonus
$200 Referall bonus
Local Home Every Day
Multiple shifts
Group Health and Dental Care options available
Weekly Pay
Direct Deposit
Oct 21 -
London - Transportation
** CDL Truck Drivers / Owner Operators - DEDICATED, REGIONAL, OTR ***
NOW HIRING Experienced CDL Truck Drivers, and Owner Operators for the following positions in the area:
* Regional / Dedicated Drivers - Home at least Weekly or more, Pay varies by position or experience, up to $1200+ per week
* OTR Tanker / Van / Reefer / Flatbed Solo & ...
Class A CDL Truck Drivers
2 Flatbed Drivers needed for Dedicated Daily Routes to the Louisville, KY/Nashville, TN/Chattanooga, TN/Knoxville, TN area.
Salary $1155 per week ($60,000 annual salary)
• Full Benefits including: Blue Cross Blue Shield Health Insurance, ...
Oct 16 -
Lexington - Transportation
Dedicated Dedicated Dedicated Truck Driver Position !!!
~~Dedicated Dedicated Dedicated Truck Driver Position !!!
Up to $69,000 per year
Drivers travel within 250-300 miles of London, KY
Weekly time at home
Flexible scheduling available
Must hold a valid CLASS A (Commercial Driver's License-CDL)
Live within 125 miles of ...
Oct 15 -
Richmond - Transportation
Oct 15 -
Lexington - Transportation
Oct 15 -
London - Transportation
Oct 9 -
Lexington - Transportation
Dump Truck Driver
Need CDL DOT Dump Truck Driver and endorsements to drive a dump truck in Lexington KY to and from asphalt plants and job sites.
Typical work week is 7:00 AM to 5:00 PM Monday through Friday occasionally Saturday
Need to have a good driving record and DOT driver history
Oct 1 -
Lexington - Construction & trades
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Taxpayers could be on the hook to pay thousands of dollars in health insurance premiums for a former county employee who retired last October.
County Clerk Jason Denny confirmed Monday that the employee retired from his office but remains an active employee on the county's list of workers receiving health care benefits.
Denny said the monthly premium totals around $400, including $125 each month for prescription coverage. Through July, the total would be well over $3,000.
A highway department employee apparently isn't the only one to violate the state's regulation on spraying weed killer on public property.
County employees in other departments, along with inmates on work release from jail, spray weed killer in the county park and around the courthouse, but do not have the required state certifications to do so.
The spraying appears to be done in numerous locations in the park, including the perimeter of the playground, skateboard park, in drainage ditches and around large drainage pipes.
A Franklin County dog that has been missing for over a month may have been spotted in Anderson County, a volunteer involved in the search said Thursday morning.
Copper, an 11-year-old Shiba Inu, was released into the wild on July 3 after being labeled as a coyote by a worker at the Franklin County Humane Society, said Barbara Murray, who is heading up the search effort for the dog.
Murray said the last reported sighting of Copper occurred on the Anderson County side of Ninevah Road.
Lawrenceburg's mayor is set for the next four years, but the council members she will be working with are yet to be determined.
In order to run in the Nov. 2 general election, candidates had to file by last Tuesday, Aug. 10.
Incumbent mayor Edwinna Baker is seeking reelection, but no one filed to challenge her this fall.
However, 10 candidates filed for a chance at a spot on the six-seat city council.
Kaitlyn Riley, a freshman on the Anderson County golf team, turned in the biggest day of her high school career as she won the Ron Zavitz Memorial Tournament, held at High Point golf course near Nicholasville on Saturday.
Riley carded a seven-over 78, one shot better than Boyle County's Rachel Pennington, to take individual honors.
A second Anderson golfer, sophomore Anna Marie Hyatt, finished fourth with an 87 over the 18 holes.
If there was any doubt about the kind of high school football progam Meade County has, Anderson County players and fans only need to think back a year when the Green Wave visited Anderson.
Suffice it to say that the nickname fit. While the Anderson County side was packed with red-clad fans, as usual, there was enough green across the field that if someone did not know better, he might have thought he had stumbled onto a Christmas decoration convention.
LEXINGTON – Anderson County did not really need a howitzer or even a tank last Wednesday.
All the Lady Bearcats needed for their shootout against Henry Clay was someone with a marksman's accuracy and a heart of steel.
After 80 excruciating, scoreless minutes, Hannah Drury answered the call.
The junior mid-fielder is far from the most intimidating figure on the Lady Bearcats. Of the five that got the chance to try to push a penalty shot past Henry Clay goalie Kayla Price, considered by some to be the best keeper in Kentucky, Drury was by far the smallest.
We've all heard about the dangers of drinking or texting while driving, but wearing flip-flops?
Although there is certainly nothing illegal about wearing them behind the wheel, flip-flops are likely the cause of a wreck last Thursday afternoon when a small car hit and became lodge beneath the rear bumper of a school bus at the intersection of Saffell Street and Glensboro Road.
No one was injured in the accident, and no students were aboard the bus.
Ethan Kelly ran for 175 yards and a touchdown and caught two passes for 37 yards and a touchdown to lead Anderson County to an impressive 46-18 win over visiting Garrard County in the Alumni Bowl on Friday night.
Kelly, a junior who had not played football since middle school, scored on a 38-yard run and averaged 10.9 yards on 16 carries.
"Just a super job," Anderson coach Mark Peach said of Kelly. "But all three of our running backs averaged over six yards a carry."
Who were you three years ago? If the you from three years ago met your present-day self, would you know each other?
These sound like crazy questions, but they are precisely the questions being addressed in a novel I'm reading, titled "Remember Me?" by Sophie Kinsella.
(Kinsella is the author of the "Shopaholic" series. "Confessions of a Shopaholic" was made into a movie starring Isla Fisher in 2009. As usual, the books are better.)
Copyright © 2014
The Anderson News is your source for local news, sports, events, and information in Lawrenceburg, KY and the surrounding area.


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Nurture Your Child Before Conception
Induced Labor and Autism: Is There a Risk?
Trustful Parenting: Turning Values Into Action
ADHD Diagnosis: Do Labels Help or Hurt?
The Myth of Self-Settling
The Milestones That Matter Most
Homeschooling: A Natural Fit for the Kinesthetic Child
...and more! Look Inside
Chiropractic care for children offers your family a solid foundation for wellness. Throughout pregnancy, birth, and childhood, the chiropractic lifestyle offers choices and benefits for your greater health and well-being. The following video and articles will help you understand the importance of the chiropractic family wellness lifestyle.


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November 6-7
Project managers must be able to communicate accurately and persuasively with people at all organizational levels. Learn to develop a communication management plan for distributing appropriate information to each stakeholder group through proper forms of media while actively managing stakeholder expectations. Learn tools and approaches for influencing outcomes, negotiating results and managing conflicts. Recognize negotiation styles including your own. Learn to communicate openly and directly within the context of a professional project manager.
St. Ambrose Professional Development can customize a training program to develop a unique program that meets the needs of your organization. For additional information, please call Stacy at 563/333-5723 or email firstname.lastname@example.com.
Get the latest on Professional Development programs through our eNewsletter. Sent conveniently to your inbox, you'll be able to plan ahead–both with your time and company.


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Michael Adams Videos
- Height: 5-8
- Weight: 181
- Age 28
- Seasons: 7
- College: Louisiana-Lafayette
NFL Rumors
Updated Seahawks' Super Bowl odds, and Russell Wilson rushing prop bet
Alshon Jeffery, Brandon Marshall return to practice; Lavonte David misses practice
Bengals QB AJ McCarron excited to be practicing
Bills Thursday injury report
Fantasy Football 2014: Who to start, who to sit for Week 12
Videos: How big a role will Josh Gordon have on Sunday? - Cleveland Browns Berea report
Hamstring injury has Lavonte David not practicing Thursday
No Larry Fitzgerald, Calais Campbell, Justin Bethel among Pro Bowl voting leaders
Chargers' Conner makes impact
Third shift open thread 11/19
Colts Expect Arthur Jones Back this Week
Cowboys LB Bruce Carter on free agency: "it will play itself out"
Emmanuel Sanders injury: Broncos receiver begins conditioning Thursday
Bengals head coach Marvin Lewis isn't worried about the surface at NRG Stadium
Julio Jones, Steven Jackson Miss Thursday Practice With Illnesses
Injury report shows signs of Cowboys' health
Out of rehab, Justin Blackmon pleads no contest to marijuana in Oklahoma
Ford Field to host Bills-Jets game on Monday night
Lions injury report: Five players miss practice
Matthews not concerned groin injury will slow him down
Falcons Sign Former Panthers, Bears Linebacker James Anderson
Matthew Stafford: 0-15 on the Road Against Winning Teams
Kansas City Chiefs @ Oakland Raiders Live Thread
Chiefs vs Raiders preview: What to watch for, storylines, match-ups
Wide receiver Marlon Brown has 'chance to make some some plays' in red zone
Bucs' Mike Evans named NFC offensive player of the week
Saints Thursday Injury Report: Full Zach Strief, Limited Pierre Thomas
What's this? Seahawks' injury reports shows … health?
AFC Playoff Picture: Week 11
Cincinnati Bengals vs Houston Texans practice and injury report
How to win free Eagles free tickets and other prizes
Turner explains decision to bring in Ben Tate
- More
- Fantasy football
- Fantasy baseball
- Fantasy basketball
- Fantasy hockey
- Sports news by city
- All sports topics
- © 2014 SPORTSOVERDOSE.COM All rights reserved.


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Report Maps Out Decarbonization Plan for U.S.
There's no technological or economic barrier standing in the way of the U.S. almost completely eliminating fossil fuels and almost fully decarbonizing by mid-century, according to the report issued by the Deep Decarbonization Pathways Project. … Read More
Climate Investments 'Falling Short' of 2°C Goal
Staving off the worst impacts of climate change by investing in clean energy and smart climate adaptations makes economic sense, but a new report shows that investments are still lagging globally. At the same time, the dropping costs of clean energy, particularly solar, mean that companies are doing more with less. The annual Global Landscape of C… Read More
World Needs to Mind the Carbon Emissions Gap
A new report suggests that policymakers better mind the gap if they want to meet the 2°C global warming threshold. But in spite of the warning, that chasm is growing as the world's carbon dioxide emissions continue to rise. To bridge the gap, the world will have to reduce emissions to reach net carbon dioxide (CO2) neutrality sometime between 2055-… Read More
Post Climate Pact, IEA Warns Fossil Fuel Trends Dire
IEA report says conservation efforts and more use of wind and solar power probably won't slash emissions enough quickly enough to prevent catastrophic climate consequences. … Read More
UN Climate Report Rings Alarm, Offers Guidance
The most sophisticated, comprehensive and succinct scientific account of the accelerating impacts of human activity on the world around us, from warming and rising oceans to the growing toll of heat stroke, was published Sunday by a United Nations panel. The picture that emerged from the 116-page synthesis of three blockbuster climate change report… Read More
Cities Designed like Ecosystems Offer Untold Gains
Of all the things people build, cities are the most important. Cities are the largest things we build, and most people now live in them. But that's not why cities are our most important invention. Cities matter because they represent our greatest hope for long-term survival, not only for humans but for all species. They offer the best chance to d… Read More
Hydropower May Be Huge Source of Methane Emissions
What if reservoirs that store water and produce electricity were among some of the world's largest contributors of greenhouse gas emissions? Scientists are searching for answers to that question, as they study how much methane is emitted into the atmosphere from man-made reservoirs built for hydropower.… Read More
From Grid Waste to Good Taste
The U.S. power grid is a vital part of the nation's infrastructure. It's also a wasteful one. Nearly two-thirds of every megawatt U.S. power plants produce never does a bit of useful work. Some of it is lost due to the natural resistance of power lines. Some is lost as heat during generation. And, perhaps surprisingly, some is lost by design when u… Read More


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Sales Manager Jobs in Durham, North Carolina
537 Durham, NC Sales Manager jobs found on Monster.Jobs 1 to 20 of 537
Overall Purpose: The sales trainer's job is to ensure that all sales professionals have thorough knowledge of our services that they sell, can effectively use closing skills, can easily overcome objections, and use consultative selling techniques. The trainer should be considered a resource for the entire sales staff, as well as the sales managers and team leaders. The sales trainer should conduc...
Description Overview: As a Sales Manager, you will support My Macy's by driving sales and selling with focus on the Macy's customer. All activities related to presenting a clean, neat and organized shopping environment for our customers are under your direction. With training, coaching and development, a team of Associates will grow following your leadership. Key Accountabilities: Sales Drive...
Start building your career and future now! About Mac Tools Mac Tools was founded in 1938 in Sabina, OH. Today, Mac Tools is an international business with Distributors and Franchisees in the United States, Canada, Europe and Japan and is part of Stanley Black & Decker, Inc., a brand synonymous with quality and impeccable customer service. Today, Mac Tools has a product line in excess of 42,000 ...
A well-established North Carolina based Metrology(Measurement) Equipment & Machine Tool Distributor with full integration and turnkey capabilities is seeking an energetic outside sales engineer specializing in their measurement products for their Eastern North Carolina territory. The ideal candidate is a self-starter, whom has passion for sales & marketing and is looking to establish life-long cus...
The Pantry Inc. Durham, NC
JOB SUMMARY: The District Sales Manager Trainee oversees the operations of a group of retail units in an assigned geographic area. Creates district implementation plans to support execution of regional and company initiatives and objectives. Motivates and develops the store management team within the district to deliver outstanding guest service in a "Fast, Clean and Friendly" environment while g...
Best Version Media is one of the fastest growing media companies in North America with growth last year of 280%. We have Account Executive openings located throughout the United States with exclusive, protected territories currently being assigned in your area. The ideal candidate will have excellent communication and relational skills, an entrepreneurial spirit and strong, persuasive closing abi...
Johnson & Johnson Durham, NC, 27701
Ethicon Division Sales Manager Durham, NC – Ethicon US LLC-9658141112 Description Ethicon US, LLC, a part of the Global Surgery Group within the Johnson & Johnson Family of Companies, is recruiting for a Division Sales Manager in Durham, NC. The Ethicon Inc. business offers a broad range of products, platforms and technologies—including, ultrasonic and advanced bipolar energy devices, sutures, ...
Macy's, Inc. Durham, NC, 27701
71746030 Overview: As a Sales Manager, you will support My Macy's by driving sales and selling with focus on the Macy's customer. All activities related to presenting a clean, neat and organized shopping environment for our customers are under your direction. With training, coaching and development, a team of Associates will grow following your leadership. Key Accountabilities: Sales Drive an...
NOW HIRING FOR A REGIONAL MANAGER POSITION! PLEASE BE ADVISED. WE ARE ONLY SEEKING APPLICATIONS FROM LICENSED INSURANCE AGENTS AT THIS TIME. EXCEPTIONAL NON-LICENSED CANDIDATES WILL BE CONSIDERED. Do you have a dominant personality and possess great drive? Are you looking for the chance to build a team of your own? Long term success in team-building demands that the system you're recruiting in h...
Job Title: FT Assistant Customer Service Sales Manager - Food Lion Job Location: Job Duties: Responsible for assisting the store team to build sales and achieve sales goals and for maintaining standards according to the Front End Standard Practice Manual, proper completion and maintenance of all store office functions and the training of Front End Sales Assistants on customer service procedures...
Job Title: Customer Service Sales Manager - Food Lion Job Location: Job Duties: Responsible for achieving and maintaining extraordinary customer service by managing customer service in all departments to build sales and achieve business goals while fostering an environment that produces high levels of customer and associate satisfaction and morale while operating the Front End according to the ...
Children's Place Durham, NC, 27701
Overview: Position Summary: The Store Manager is responsible for leading store teams in driving sales, brand loyalty, providing exceptional customer service as well as recruiting and developing top retail talent. This position has full accountability for the key financial results of the store and is responsible for the overall leadership and development of the store by building an independent, hi...
Appia Durham, NC, 27701
The Ad Sales Account Manager is responsible for supporting Appia's Ad Sales Team in all areas from proposal to reporting. This role will coordinate the launch of advertising campaigns, managing client relationships through day-to-day contact with the client and maintaining advertising campaigns with a heavy focus on the advertiser and network goals, to support the growth and procurement of revenue...
As the Retail Sales Manager you are a key member of the retail store management team. The Sales Manager reports to the Store Manager and leads a team of retail staff to deliver on business goals of sales, memberships, and service. The Sales Manager spends most of their time as an active, visible leader, motivating, directing, and coaching hourly staff. Specific responsibilities include: • Leverag...
Job Title: Deli/Bakery Sales Manager - Food Lion Job Location: Job Duties: Ensure that Food Lion service standards are met. Responsible for sales, profits and associates of the Deli/Bakery Department. Responsible for maintaining standards according to the Deli/Bakery Standard Practice Manual, maximizing sales by providing extraordinary customer service and minimizing shrink through proper utili...
Marketstar Research Triangle Park, NC
Marketstar currently has an opening available in the Research Triangle Park, NC office for an Inside Sales Account Manager (ISAM) responsible for driving sales to small and medium businesses (SMB's). The ideal ISAM is a success-driven salesperson who builds strong relationships with multiple stakeholders, and enjoys a dynamic and changing environment. RESPONSIBILITIES : Generate revenue through ...
Cisco Systems , Inc. RESEARCH TRIANGLE PAR, NC
Senior Manager, Sales Acquisition Integration WW Sales Strategy & Planning works on selected, high impact business and go-to-market opportunities for Cisco's senior sales leaders. Acquisitions and divestitures are challenging, highly visible, global, and cross-functional in nature, requiring strong business acumen and leadership skills to manage effectively. The Senior Manager will be responsibl...
NOW HIRING FOR A REGIONAL MANAGER POSITION! PLEASE BE ADVISED. WE ARE ONLY SEEKING APPLICATIONS FROM LICENSED INSURANCE AGENTS AT THIS TIME. EXCEPTIONAL NON-LICENSED CANDIDATES WILL BE CONSIDERED. Do you have a dominant personality and possess great drive? Are you looking for the chance to build a team of your own? Long term success in team-building demands that the system you're recruiting in h...
SUMMARY The Senior Assistant Store Manager is responsible for assisting the store manager on all operational duties and providing superior customer support for quality service, customer satisfaction and driving profitability. ESSENTIAL DUTIES AND RESPONSIBILITIES Leads recruiting efforts for all available charmer positions with responsibility for the interview process. Makes final decision on a...
SUMMARY The General Sales Manager will have the primary responsibility for managing all aspects of a Charming Charlie retail store. This key position will create a selling environment that is focused on customer service and achieving business results. You must have a personality and attitude that creates an environment where Associates enjoy coming to work every day and customers love to shop. We...
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Sales Career Tools
Sales Manager
$21,840.00 - $120,000.00
Typical Salary for Sales Manager in Durham
(19 Respondents)
Source: Monster.com Careerbenchmarking Tool
Education / Training
Some College Coursework Completed
High School
(17 Respondents)
Source: Monster.com Careerbenchmarking Tool
Sales Manager
Directs distribution of a product; sells products by implementing sales plans; supervises sales staff; analyzes sales statistics; forecasts future sales; manages customer relationships.
Rate of Growth
8.30 %
Size of Industry in 2006:
Source: Bureau of Labor Statistics, May 2006
Related Skills
Active listening
Building Relationships
Decision Making
Related Duties
Maintains professional and technical knowledge by attending educational workshops; reviewing professional publications; establishing personal networks; participating in professional societies.
Maintains sales staff job results by counseling and disciplining employees to develop and control sales and service programs; planning, monitoring, and appraising job results.
Popular Sales Manager Articles
Sample Resume for a Sales Manager
Does your resume effectively sell your track record in sales? This resume sample for a midlevel sales manager will show you how it can.
Marketing Jobs
Jobs in marketing are wide-ranging, encompassing all forms of media and a variety of disciplines and specialties. Explore marketing careers now.
Sample Resumes by Industry
Writing a resume specific to your industry is a great way to be a star candidate. If you need help customizing your resume to your field, check out these resume examples for various careers.
The Jobs Behind the Big (Football) Game
Even though you're no professional football player, you can still be part of the action come game day. Check out this list of jobs that make each game possible.
Sample Resume for a Retail Manager
Does your resume do a good job selling your skills for retail manager jobs to potential employers? Compare it to this sample resume to find out.


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East Dennis House Rental Photos and Description
3 Bedrooms, 2 Baths, Sleeps 6
2015 PRIME SEASON RATE: $1650.00. SUNDAY TO SUNDAY RENTAL!!!! Avoid the Saturday traffic when you rent this elegant Northside home. An easy drive to Sesuit Harbor, Princess Lake, Corporation and Mayflower beaches. Lovely, private and tranquil setting with manicured yard and mature plantings. This home offers a formal living room and dining room as well as a casual family room and delightful sun porch. The kitchen includes a dishwasher, microwave, toaster oven and laundry area. There is an adjoining dining area with sliders to a large rear deck. Ceiling fans are in every bedroom and the family room. Home offers two full bathrooms, two TV's, cable, DVD Wifi, and one window a/c unit in the master bedroom. A gas grill, patio table with chairs and umbrella and chaise lounges are provided.
Bedroom # 1: 1 King
Bedroom # 2: 2 Twins
Bedroom # 3: 2 Twins
Maximum Occupancy 6
Maximum Vehicles 3
Square footage 2000


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Rockland couple recount trek through deadly blizzard, mass hiking tragedy in ...
Bangor Daily News
The Rockland couple, who were caught in the blizzard with more than 300 other hikers along one of the most popular trails around Annapurna, the world's 10th highest peak, said they survived because they were prepared for bad weather and knew they had ...
and more »
Stocks aim for more records; Tesla talking to BMW; 'Hunger Games' debut ...
Yahoo Canada Finance - Insight (blog)
The Annapurna Circuit is part of the Annapurna mountain range of the Himalayas in central Nepal. Of all … More » The ineffable Himalayan glory of Annapurna · The stupidest smugglers in the world. The amount of things, including live animals, that travellers ...
Impoverished seniors complain they have been deprived of benefits of ...
IMPHAL, November 23: Despite the generous Annapurna scheme of Central government implemented for the people below poverty line, little or no benefits of the scheme have been reaching the beneficiaries since August 2012 claimed a group of ...
Motorcycle borne miscreants loot traders
Free Press Journal
Indore: Despite the police efforts, loots are still occurring in Annapurna area. On Wednesday night, a trader moving on his motorcycle was shoved by three motorcycle borne miscreants. While the trader tried to regain balance, the accused looted him. Although ...
Microfinance Monitor
Nagarjuna Next Film 'Soggade Chinni Nayana' Launched
Microfinance Monitor
The shooting of the film was launched on Wednesday tentatively and Nagarjuna plays the dual role of grandfather and grandson. "The film was officially launched in Annapurna Studios with a puja. Regular shooting will start shortly in Rajahmundry," a source ...
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