A release mechanism for telescoping slide assembly including an outer member and an inner member is provided. The mechanism comprises a flexible strip of substantially triangular transverse cross section mounted on the inner member, the flexible strip including two flexible arms each extended from either end of a bottom plate thereof, two opposite recesses, and two locking lugs on the sides of either recess; and an engagement section on outer end of intermediate member, the section including an aperture and a projection on the edge of aperture. In the use position, the locking lugs contact the inner wall of the intermediate member while sliding, and the recesses are clung to both sides of the projection when the inner member has reached a predetermined end of the use position, thus blocking movement of the inner member relative to the intermediate member. Moreover, either arm may be depressed to disengage recess from projection. Hence, inner member may be moved away from outer member or retract inner member. The mechanism can effect a locking or unlocking of inner member in either extending or retracting.

1. Field of Invention
The present invention relates to telescoping slide assembly and more particularly to a flexible strip for slide release mechanism with improved characteristics.
2. Related Art
Conventionally, a slide is widely employed to enable the relative movement of a drawer and a cabinet, a computer desk and a keyboard shelf, or the like. A conventional slide comprises an outer member, an intermediate member, and an inner member. For example in the drawer and cabinet configuration, outer member is fixed to the wall of cabinet, inner member is fixed to the side of drawer, and intermediate member is slidably received in outer member for supporting inner member in a sliding relationship. A well known ball bearing mechanism is employed to interconnect above any two adjacent members. Hence, inner member and intermediate member may coaxially move respect to outer member. Thus drawer is permitted to remove to its maximum extension or retract into the cabinet. Typically, a stop mechanism such as latch is employed to lock slide when it reaches its maximum extension. At this time, intermediate member and outer member are held in place by the latch. Hence, drawer carried by inner member is also held in this place. One such latch based release mechanism for slide assembly in cooperation with inner, intermediate, and outer members is disclosed in U.S. Pat. No. 4,998,828 entitled xe2x80x9cOver And Under Telescoping Slide Assemblyxe2x80x9d, which is incorporated herein by reference. In the ""828 Patent, the slide assembly comprises a cabinet slide member, a drawer slide member, and an intermediate slide member slidably connected the cabinet inner member. A spring lock assembly is mounted on inner end of drawer slide member. A pair of hooks are provided at inner end of the intermediate slide member projected toward drawer slid e member. Spring lock assembly comprises a pair of flexible strips and a pair of receiving apertures. Hence, drawer slide member and its attached drawer may be sliding relative to the intermediate slide member when hooks are clear from the receiving apertures or depressing the flexible strips to disengage from the receiving apertures. However, such design does not block movement of drawer and drawer slide member while de pressing the flexible strips. Thus drawer is susceptible to drop from cabinet if enough care is not taken. The size of receiving aperture is enlarged for permitting the tab of flexible strip to have a sufficient time to fall into engagement therein since the sliding speed of slide may be fast. However, a gap between the receiving aperture and the tab of flexible strip is thus created. This is undesirable for securing drawer to cabinet.
Moreover, U.S. Pat. Nos. 4,993,847 and 5,085,523 both disclosed a similar slide release mechanism. In brief, a flexible strip is mounted on a first slide track fixed to a drawer. A button and a pin-receiving aperture are provided on flexible strip. A pin on a second slide track is activated to fall into the aperture when first slide track and its attached drawer are slid to a use position, thus locking the slide assembly in the use position. In a reverse operation, user may depress button to deform flexible strip for disengaging pin from the aperture. As a result, drawer may be retracted into or removed from cabinet. Such prior art is disadvantageous for employing many small components. Further, it does not block movement of drawer and first slide track while depressing the flexible strip. Thus drawer is susceptible to drop from cabinet if enough care is not taken.
It is therefore an object of the present invention to provide a release mechanism for slide assembly capable blocking movement of inner member and its attached drawer in either extending or retracting, thus ensuring a secure operation.
It is another object of the present invention to provide a precisely positioned release mechanism having reduced components.
The advantages of the present invention are realized by providing a release mechanism for telescoping slide assembly including an outer member and an inner member is provided. The mechanism comprises a flexible strip of substantially triangular transverse cross section mounted on the inner member, the flexible strip including two flexible arms each extended from either end of a bottom plate thereof, two opposite recesses, and two locking lugs on the sides of either recess; and an engagement section on outer end of intermediate member, the section including an aperture and a projection on the edge of aperture. In the use position, the locking lugs contact the inner wall of the intermediate member while sliding, and the recesses are clung to both sides of the projection when the inner member has reached a predetermined end of the use position, thus blocking movement of the inner member relative to the intermediate member. Moreover, either arm may be depressed to disengage recess from projection. Hence, inner member may be moved away from outer member or retract inner member. The mechanism can effect a locking or unlocking of inner member in either extending or retracting.
Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

Flexible strip for slide release mechanism


A digital input signal is input to a real part calculator and an imaginary part calculator. The real part calculator comprises an M-stage shift register formed of an M number of series-connected D-type latch circuits and for delaying the input signal in a stepwise manner where M represents 2 or more positive integers. The imaginary part calculator comprises an N number of series-connected D-type latch circuits for delaying the input signal in a stepwise manner, coefficient registers for storing coefficients corresponding to the respective latch circuits, multipliers for multiplying the output of the latch circuit and the corresponding coefficient thereof, and an adder for adding together all the outputs of the multipliers. Here, N denotes 2 or more positive integers. If N is an odd number, M=(N+1)/2, and, M=N/2 or (N/2)+1 if N is an even number. The coefficient registers store coefficients for enabling the digital filter to perform a Hilbert transformation. The real and imaginary part signals output from the real and imaginary part calculators are input to a phase calculator. The phase calculator comprises a divider for dividing the imaginary part signal by the real part signal, and a calculator for calculating an arctangent of the result of the division. Alternatively, the real and imaginary part signals may be supplied to an envelope calculator, which calculates the root-mean-square of the real and imaginary part signals.

This invention relates to a digital signal processing device capable of calculating real and imaginary parts of an input signal and evaluating the phase and envelope of the input signal from the real and imaginary parts calculated.
In the case of an ultrasonic Doppler blood flowmeter, it is necessary that the phase of a Doppler signal be calculated so as to detect the speed and direction of flow of blood cells. The conventional phase detection method usually employs the Fourier transformation. According to the Fourier transformation method, however, data evaluation cannot begin until all the data to be used for Fourier transformation have been stored in memory. As a result, the corresponding storage time becomes a wait time and therefore increases the length of time required to perform such a transformation. In order for the ultrasonic Doppler blood flowmeter to detect and display the speed of bloodflow in real time, it is necessary for the number of data in a Doppler signal for Fourier transformation to be reduced, thereby reducing the accuracy of the readings obtained. Even if the data of a region not calculated in this way is to be evaluated by means of an interpolation method, any better accuracy is not obtained from this method and thus a time-consuming operation results. Furthermore, in typical ultrasonic diagnostic device it is necessary to detect the envelope of echo signal in order to obtain the tomographic image. The envelope of the echo signal represents the luminance of the image along a scanning line. Therefore, the tomographic image is obtained by scanning the object and by arranging the images with the detected luminance in a two-dimensional manner.
In the conventional method the envelope has been obtained by detecting the echo signal (analog signal) and passing the detected signal through a low-pass filter. However, since the waveform of the echo signal is degraded by its passage through the low-pass filter, the diagnostic data thus obtained is rendered useless due to a lowering of the spatial, densIty resolution of the ultrasonic image, as well as a lowering of the S/N ratio.

Digital signal processing device for calculating real and imaginary parts of an input signal


A medicament dispensing device, a medicament magazine thereof, and a method of removing a medicament from the medicament magazine. The inhaler has a mouthpiece (9) and an air channel (4) connected thereto, as well as a medicament magazine with at least one medicament chamber containing a powdered medicament. A drive current is produced in the air channel, while a vacuum flow (5′) can be produced by the drive current and a constriction formed in the air channel. This narrowest part of the air channel that produces the vacuum flow is connected to a removal opening (2) which communicates with a control opening (3), in order to form an emptying current through the control opening via the removal opening. In a preferred embodiment the at least one medicament chamber including the control opening, the removal opening and a fill opening are housing in the one-piece medicament magazine.

1. Field of the Invention
The invention relates to the field of medicament dispensing devices with a multi-dose magazine, particularly multi-dose powder inhalers, and relates to a medicament dispensing device according to the preamble of the independent claim. Also claimed is a medicament magazine for use in the medicament dispensing device, and a method of removing a medicament, particularly a powdered medicament.
Inhalers are known from the prior art in which a connection is made directly to a medicament chamber by means of a vacuum flow produced by inhaling (Venturi) and a powdered medicament contained therein is removed. In U.S. Pat. No. 6,655,381 a powdered medicament is placed in wells arranged in a circle in an annular magazine. A seal that closes off the wells is removed substantially in its entirety and a Venturi tube is arranged parallel to the magazine with the constriction above the well. Attached to the Venturi tube is a longer turbulence chamber which is needed as the medicament is essentially removed from the well all in one go. With this device it is not possible to achieve accurate dosing of a medicament or adjustment to different dosages.
2. Description of Related Art
In addition, there are various inhalers in which a medicament chamber is opened by piercing. However, openings in a film made by piercing are not very precisely defined, which means that on the one hand the precise amount of a medicament removed is not known and also differences occur between successive removals. This is undesirable particularly with medicaments the activity of which depends to a very high degree on the dosage.
In order to achieve the best possible turbulence in a medicament and thereby dissolve the carrier material and the active substance itself, in EP 1 475 115 and GB 2 340 758, a medicament chamber is essentially divided into an entry and exit chamber which are joined together by a constricted passage. A medicament is placed only in the entry chamber. By piercing or introducing cannulas, an air flow is produced through the medicament chamber from the entry chamber through the constriction into the exit chamber and out of the medicament chamber. In EP 1 475 115, for improved emptying of the medicament chamber, the entry and exit chamber are each provided with two openings. In both specifications, the openings in the chambers are defined by the piercing.
In U.S. Pat. No. 5,715,810 a medicament chamber incorporated in an annular magazine is pierced on both sides. One piercing cannula is attached to a Venturi current, so as to produce an air flow through the chamber. The removal takes place in one step and cannot be metered, or can only be metered poorly. Here, too, the chambers are defined by piercing and pins used for this.
In WO 03/045483 a medicament chamber is pierced and a medicament contained therein is emptied out using an air flow produced by a compressed air source.
EP 0 547 429 discloses a cylindrical medicament magazine in which a fresh medicament chamber is brought into registry with a removal opening inside the apparatus by a screwing movement. In the apparatus, the air flow is subdivided: while one part empties the medicament chamber, the other part is passed through the apparatus and is combined with the medicament air current as an encircling air current.
In WO 2005/002654 an air flow is injected through a medicament chamber. Individual medicament pouches are housed in an annular magazine. During use the pouches are pushed out of the magazine from behind, thereby severing a sealing film and are coupled with a removal mechanism. At the same time an air current is guided into and through the pouch at the maximum possible speed. To trigger aggregation of a powder and prevent medicament from being carried forward into successive inhalations, an individual channel is provided downstream of each pouch. With an additional bypass channel that circumvents the pouch and also opens into a mouthpiece, the total volume of air inhaled is increased and inhalation facilitates or guarantees a sufficient air current being present to transport the medicament to the user. Owing to the fact that some of the air current is deflected through the bypass channel, the air current through the pouch is reduced, so that the removal process is prolonged. The removal of the medicament can thus be spread over a somewhat longer period of time instead of all being removed at once.
The powder inhaler from WO 2005/002654 is relatively complicated in construction. A number of different parts are present, some of which move and have to be coordinated with one another. Moreover, the removal of the medicament is not triggered by an actual Venturi principle, but rather there is an intake current passing directly through the medicament pouches, and this can be weakened by a bypass flow.
The aim of the invention is therefore to provide a medicament dispensing device, a medicament magazine for use in such a medicament dispensing device and a method of removing a medicament form a medicament chamber in which the removal is based on the Venturi principle and the amount taken out can be metered accurately and reproducibly.
This aim is achieved by the medicament dispensing device, the medicament magazine, and the method, as defined in the claims.
The invention is based on the principle known from U.S. Pat. No. 6,655,381, for example, of applying a Venturi-like vacuum flow to a medicament chamber and sucking the medicament contained therein out of the chamber by the vacuum and transporting it with the flow towards a mouthpiece. There, the medicament travels with the air current in the lungs of the user inhaling it.
In the device and method according to the invention, a drive current is now produced in an air channel, which as a result of a constriction in the air channel produces a vacuum flow in this region. The narrowest part of the air channel causing the reduced pressure flow is connected to a removal opening of a medicament chamber. The removal opening is connected to a control opening, so that an emptying current is formed through the control opening via the removal opening and through the medicament chamber. The emptying current is not connected to the drive current before entering the medicament chamber, but combines with the drive current after leaving the removal opening, so that a medicament carried along with the emptying current is transported with the drive current towards the mouthpiece.
The removal and control openings are preferably integrated directly in a medicament magazine. If the openings or the medicament magazine as a whole are produced by injection moulding from plastics, for example, these openings are very precisely defined, in a way which is not possible when an opening is produced by piercing, for example. By integrating the removal and control openings in the medicament magazine, these two openings are pre-defined and are fixed both before and after opening a medicament chamber.
The control and removal openings form a major part of a throttle arrangement by which it is possible to control the emptying current and hence to vary the quantity of medicament removed per unit of time. Other elements of the throttle arrangement with different effects may be the inner configuration of the medicament chamber itself, and the construction of the air channel connected to the removal opening, particularly its diameter.
As a result, the removal can be deliberately controlled, is precisely defined and above all reproducible. A throttle effect and hence an emptying current can be deliberately selected on the basis of the accurately defined but variable elements such as the control opening, removal opening, inner configuration of the medicament chamber and can also easily be changed to other dosages, quantities and types of medicaments.
The inhaler may also have at least one bypass opening to assist the inhalation process, e.g. for children or people with weakened lungs. This bypass opening serves to form a bypass flow which also leads to the mouthpiece and is preferably arranged downstream of a removal opening in the direction of the mouthpiece. However, it does not have any direct influence on a defined correlation between the vacuum flow, the removal opening and control opening.
A medicament chamber is preferably constructed so that at least some of the emptying current flows away over the medicament contained in the medicament chamber. By a suitable inner configuration of the medicament chamber it is also possible to influence the disaggregation and dispersion of a medicament. For example, additional turbulence can be introduced into an emptying current by means of a turbulence element, which is preferably formed by at least one part of the wall of the medicament chamber itself. This can increase the throttling effect or, if necessary, reduce it.
In the medicament chamber an additional vacuum flow can be produced, for example by means of a special configuration of a chamber wall or by means of a turbulence element. This is preferably arranged in a direct line between the control and removal openings, such that a medicament located on the floor of the medicament chamber is detached by this additional vacuum flow in the chamber. This can be achieved by, for example, the medicament chamber itself forming a kind of Venturi tube in all or part of the region between the control and removal openings.
A medicament magazine typically has a fill opening in addition to a control and removal opening. This fill opening is preferably formed independently of the other two openings in the magazine. This has the advantage that the fill opening can be very large, to assist with the filling operation. The fill opening is closed off, preferably sealed with a foil, after the introduction of a powder. If the medicament magazine is constructed as an annular magazine with a plurality of medicament chambers arranged in a circle therein, the control and removal openings of each chamber are spaced from one another, preferably on one side of the magazine, while the fill opening is arranged on the opposite side of the magazine. Thus, the opening of the control and removal openings is also independent of the removal of a sealing foil. Preferably a medicament magazine has a plurality of medicament chambers and single doses contained therein. The number is preferably in the range from 1 to 100 or up to 200 single doses, preferably in the range from 1-60, for example between 7-180 or 14-150, e.g. 30-120, 45-100, 30, 90, 60, 120. For inhalers the maximum number of single doses is preferably 60, for reasons of convenience and therapy.
An inhaler with a medicament magazine of this kind is very versatile in use. Besides the various possibilities of coordination and deliberate and very precise dosing possibilities, particularly their reproducibility, there is also the option of using the inhaler with a wide range of amounts and types of medicament. It is relatively simple to use a different medicament magazine, e.g. with a medicament chamber with a different, e.g. greater or smaller, capacity. If a removal opening is accurately defined by the medicament magazine itself, an adjacent (vacuum) opening in the Venturi suction tube may also be made larger without affecting the removal opening and hence the emptying current. As a result an inhaler can also be used with different medicament magazines, e.g. those with differently designed removal openings. Owing to the fact that only one removal opening has to be coupled at the inhaler end, the remainder of the construction of the inhaler and also the medicament chamber, in relation to a removal mechanism, is substantially independent of the medicament magazine and vice versa. In particular, a medicament chamber may be very elongated, may have an angle, etc., and a control opening may be arranged accordingly at different locations in the magazine. This is possible as the control opening is not directly connected to the arrangement of the Venturi tube, and in particular, the drive current produced in the Venturi tube and the emptying current formed by the coupling of the vacuum flow to the magazine have a different origin.
In the inhaler according to the invention essentially any kind of opening mechanism is possible: a medicament chamber can be opened before the removal of the medicament by piercing, scraping or peeling off a sealing foil that closes off the medicament chamber. A medicament chamber is designed accordingly, preferably such that the removal and control opening, which may also be referred to as control openings, are not affected by the opening mechanism. In particular, they are not affected by openings in the sealing foil itself or by an opening mechanism of the apparatus which produces such openings. This may be achieved for example by removing a sealing foil entirely from the control openings before the medicament is taken out, or by making an opening in a sealing foil so big that its effect on the control openings is negligible.
In one embodiment of the magazine, a medicament is emptied into a preliminary chamber, the preliminary chamber having a corresponding control and removal opening which is connected to a vacuum flow for removing the medicament. For this purpose, a medicament may be sealed in its own medicament chamber with a sealing foil which is preferably opening by an opening means that may be installed in the chamber itself. In this embodiment this fill opening is arranged substantially on the same side as the control openings. The preliminary chamber may be an integral part of the medicament chamber or the medicament magazine, or it may be an integral part formed on an air channel. The advantage of the first variant is that a new unused chamber is available each time medicament is taken.
In a preferred embodiment of the inhaler, two medicament chambers are joined together through a common mouthpiece. In this way, the number of single doses of medicament can be doubled. For this, the individual medicament chambers of the two magazines are preferably arranged offset from one another. However, it is also possible, when removing the medicament, to open one chamber of each magazine and take one medicament from each. This is particularly advantageous if two medicaments have to be taken which cannot be stored together, or if every second time a double quantity of a medicament or medicament mixture has to be taken.
For producing a medicament magazine and optionally also certain parts of a device, pharmaceutically permitted materials are preferably used. The films used may be multi-layer films, for example, which are suitable as films for peeling or piercing or for scraping off. Multi-layer films usually have a layer of PE, PP or PVC and an aluminium layer. Depending on the particular requirement, a film is made more stable or tear-resistant, and this is pref done by incorporating a PET layer. In preferred material combinations, an outer layer of a film comprises the same material as an injected-moulded magazine, for example. In this way it is possible to seal or weld the different elements of a medicament magazine with the same materials. It is also possible to use sealing lacquer, e.g. heat-sealing lacquer. As a result, there are more possible material combinations for the individual elements. A sealing lacquer is applied, for example, to a film and/or to a magazine that is to be closed off. It is also possible for a foil to have a layer of sealing lacquer directly. The strength of the seal is preferably also optimally tailored to the use, so that, for example, a peelable film adheres directly but removably to an elements which is to be sealed.
The compounds specified below may be used in the apparatus according to the invention on their own or in combination. In the compounds specified below, W is a pharmacologically active substance and (for example) is selected from among the betamimetics, anticholinergics, corticosteroids, PDE4-inhibitors, LTD4-antagonists, EGFR-inhibitors, dopamine agonists, H1-antihistamines, PAF-antagonists and PI3-kinase inhibitors. Moreover, double or triple combinations of W may be combined and used in the apparatus accin. Combinations of W might be, for example:                W denotes a betamimetic, combined with an anticholinergic, corticosteroid, PDE4-inhibitor, EGFR-inhibitor or LTD4-antagonist,        W denotes an anticholinergic, combined with a betamimetic, corticosteroid, PDE4-inhibitor, EGFR-inhibitor or LTD4-antagonist,        W denotes a corticosteroid, combined with a PDE4-inhibitor, EGFR-inhibitor or LTD4-antagonist        W denotes a PDE4-inhibitor, combined with an EGFR-inhibitor or LTD4-antagonist        W denotes an EGFR-inhibitor, combined with an LTD4-antagonist.
The compounds used as betamimetics are preferably compounds selected from among albuterol, arformoterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, isoetharine, isoprenaline, levosalbutamol, mabuterol, meluadrine, metaproterenol, orciprenaline, pirbuterol, procaterol, reproterol, rimiterol, ritodrine, salmefamol, salmeterol, soterenol, sulphonterol, terbutaline, tiaramide, tolubuterol, zinterol, CHF-1035, HOKU-81, KUL-1248 and    3-(4-{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-hexyloxy}-butyl)-benzyl-sulphonamide    5-[2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinoline-2-one    4-hydroxy-7-[2-{[2-{[3-(2-phenylethoxy)propyl]sulphonyl}ethyl]-amino}ethyl]-2(3H)-benzothiazolone    1-(2-fluoro-4-hydroxyphenyl)-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)-on    1-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-tert.-butylamino)ethanol    6-hydroxy-8-{1-hydroxy-2-[2-(4-methoxy-phenyl)-1,1-dimethyl-ethylamino]-ethyl}-4H-benzo[1,4]oxazin-3-one    6-hydroxy-8-{1-hydroxy-2-[2-(ethyl 4-phenoxy-acetate)-1,1-dimethyl-ethylamino]-ethyl}-4H-benzo[1,4]oxazin-3-one    6-hydroxy-8-{1-hydroxy-2-[2-(4-phenoxy-acetic acid)-1,1-dimethyl-ethylamino]-ethyl}-4H-benzo[1,4]oxazin-3-one    8-{2-[1,1-dimethyl-2-(2,4,6-trimethylphenyl)-ethylamino]-1-hydroxy-ethyl}-6-hydroxy-4H-benzo[1,4]oxazin-3-one    6-hydroxy-8-{1-hydroxy-2-[2-(4-hydroxy-phenyl)-1,1-dimethyl-ethylamino]-ethyl}-4H-benzo[1,4]oxazin-3-one    6-hydroxy-8-{1-hydroxy-2-[2-(4-isopropyl-phenyl)-1,1dimethyl-ethylamino]-ethyl}-4H-benzo[1,4]oxazin-3-one    8-{2-[2-(4-ethyl-phenyl)-1,1-dimethyl-ethylamino]-1-hydroxy-ethyl}-6-hydroxy-4H-benzo[1,4]oxazin-3-one    8-{2-[2-(4-ethoxy-phenyl)-1,1-dimethyl-ethylamino]-1-hydroxy-ethyl}-6-hydroxy-4H-benzo[1,4]oxazin-3-one    4-(4-{2-[2-hydroxy-2-(6-hydroxy-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-ethylamino]-2-methyl-propyl}-phenoxy)-butyric acid    8-{2-[2-(3,4-difluoro-phenyl)-1,1-dimethyl-ethylamino]-1-hydroxy-ethyl}-6-hydroxy-4H-benzo[1,4]oxazin-3-one    1-(4-ethoxy-carbonylamino-3-cyano-5-fluorophenyl)-2-(tert-butylamino)ethanol    2-hydroxy-5-(1-hydroxy-2-{2-[4-(2-hydroxy-2-phenyl-ethylamino)-phenyl]-ethylamino}-ethyl)-benzaldehyde    N-[2-hydroxy-5-(1-hydroxy-2-{2-[4-(2-hydroxy-2-phenyl-ethylamino)-phenyl]-ethylamino}-ethyl)-phenyl]-formamide    8-hydroxy-5-(1-hydroxy-2-{2-[4-(6-methoxy-biphenyl-3-ylamino)-phenyl]-ethylamino}-ethyl)-1H-quinolin-2-one    8-hydroxy-5-[1-hydroxy-2-(6-phenethylamino-hexylamino)-ethyl]-1H-quinolin-2-one    5-[2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one    [3-(4-{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-hexyloxy}-butyl)-5-methyl-phenyl]-urea    4-(2-{6-[2-(2,6-dichloro-benzyloxy)-ethoxy]-hexylamino}-1-hydroxy-ethyl)-2-hydroxymethyl-phenol    [3-(4-{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-hexyloxy}-butyl)-benzylsulphonamide    3-(3-{7-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-heptyloxy}-propyl)-benzylsulphonamide    4-(2-{6-[4-(3-cyclopentanesulphonyl-phenyl)-butoxy]-hexylamino}-1-hydroxy-ethyl)-2-hydroxymethyl-phenol    N-adamantan-2-yl-2-(3-{2-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenye-ethylamino]-propyl}-phenyl)-acetamide,optionally in the form of the racemates, enantiomers, diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates or hydrates thereof. According to the invention the acid addition salts of the betamimetics are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.
The anticholinergics used are preferably compounds selected from among the tiotropium salts, preferably the bromide salt, oxitropium salts, preferably the bromide salt, flutropium salts, preferably the bromide salt, ipratropium salts, preferably the bromide salt, glycopyrronium salts, preferably the bromide salt, trospium salts, preferably the chloride salt, tolterodine. In the above-mentioned salts the cations are the pharmacologically active constituents. As anions the above-mentioned salts may preferably contain the chloride, bromide, iodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate or p-toluenesulphonate, while chloride, bromide, iodide, sulphate, methanesulphonate or p-toluenesulphonate are preferred as counter-ions. Of all the salts the chlorides, bromides, iodides and methanesulphonates are particularly preferred.
Other preferred anticholinergics are selected from among the salts of formula AC-1
wherein X− denotes an anion with a single negative charge, preferably an anion selected from among the fluoride, chloride, bromide, iodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate, preferably an anion with a single negative charge, particularly preferably an anion selected from among the fluoride, chloride, bromide, methanesulphonate and p-toluenesulphonate, particularly preferably bromide, optionally in the form of the racemates, enantiomers or hydrates thereof. Of particular importance are those pharmaceutical combinations which contain the enantiomers of formula AC-1-ene
wherein X− may have the above-mentioned meanings. Other preferred anticholinergics are selected from the salts of formula AC-2
wherein R denotes either methyl or ethyl and wherein X− may have the above-mentioned meanings. In an alternative embodiment the compound of formula AC-2 may also be present in the form of the free base AC-2-base.

Other specified compounds are:    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;    scopine 9-hydroxymethyl-xanthene-9-carboxylate methobromide,
The above-mentioned compounds may also be used as salts within the scope of the present invention, wherein instead of the methobromide the salts metho-X are used, wherein X may have the meanings given hereinbefore for X−.
As corticosteroids it is preferable to use compounds selected from among beclomethasone, betamethasone, budesonide, butixocort, ciclesonide, deflazacort, dexamethasone, etiprednol, flunisolide, fluticasone, loteprednol, mometasone, prednisolone, prednisone, rofleponide, triamcinolone, RPR-106541, NS-126, ST-26 and    (S)-fluoromethyl 6,9-difluoro-17-[(2-furanylcarbonyl)oxy]-11-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carbothionate    (S)-(2-oxo-tetrahydro-furan-3S-yl)6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-propionyloxy-androsta-1,4-diene-17-carbothionate,    cyanomethyl 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-(2,2,3,3-tetramethylcyclopropylcarbonyl)oxy-androsta-1,4-diene-17β-carboxylateoptionally 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. Any reference to steroids includes a reference to any salts or derivatives, hydrates or solvates thereof which may exist. Examples of possible salts and derivatives of the steroids may be: alkali metal salts, such as for example sodium or potassium salts, sulphobenzoates, phosphates, isonicotinates, acetates, dichloroacetates, propionates, dihydrogen phosphates, palmitates, pivalates or furoates.
PDE4-inhibitors which may be used are preferably compounds selected from among enprofyllin, theophyllin, roflumilast, ariflo (cilomilast), tofimilast, pumafentrin, lirimilast, arofyllin, atizoram, D-4418, Bay-198004, BY343, CP-325,366, D-4396 (Sch-351591), AWD-12-281 (GW-842470), NCS-613, CDP-840, D-4418, PD-168787, T-440, T-2585, V-11294A, Cl-1018, CDC-801, CDC-3052, D-22888, YM-58997, Z-15370 and    N-(3,5-dichloro-1-oxo-pyridin-4-yl)-4-difluoromethoxy-3-cyclopropylmethoxybenzamide    (−)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-difluoromethoxy-phenyl)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    9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-thienyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine    9-cyclopentyl-5,6-dihydro-7-ethyl-3-(tert-butyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridineoptionally in the form of the racemates, enantiomers or diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts thereof, the solvates and/or hydrates thereof. According to the invention the acid addition salts of the PDE4 inhibitors are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.
The LTD4-antagonists used are preferably compounds selected from among montelukast, pranlukast, zafirlukast, MCC-847 (ZD-3523), MN-001, MEN-91507 (LM-1507), VUF-5078, VUF-K-8707, L-733321 and    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    [2-[[2-(4-tert-butyl-2-thiazolyl)-5-benzofuranyl]oxymethyl]phenyl]acetic acidoptionally 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. According to the invention these acid addition salts are preferably selected from among the hydrochloride, hydrobromide, hydroiodide, hydrosulphate, hydrophosphate, ydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate. By salts or derivatives which the LTD4-antagonists may optionally be capable of forming are meant, for example: alkali metal salts, such as for example sodium or potassium salts, alkaline earth metal salts, sulphobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates, palmitates, pivalates or furoates.
EGFR-inhibitors which may be used are preferably compounds selected from among cetuximab, trastuzumab, ABX-EGF, Mab ICR-62 and    4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-cyclopropylmethoxy-quinazoline    4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-diethylamino)-1-oxo-2-buten-1-yl]-amino}-7-cyclopropylmethoxy-quinazoline    4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-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-cyclopropylmethoxy-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-{[4-((R)-2-methoxymethyl-6-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-cyclopropylmethoxy-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-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-cyclopentyloxy-quinazoline    4-[(R)-(1-phenyl-ethyl)amino]-6-{[4-(N,N-bis-(2-methoxy-ethyl)-amino)-1-oxo-2-buten-1-yl]amino}-7-cyclopropylmethoxy-quinazoline    4-[(R)-(1-phenyl-ethyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-ethyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline    4-[(R)-(1-phenyl-ethyl)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,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((R)-tetrahydrofuran-3-yloxy)-quinazoline    4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-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-cyclopropyl-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-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-[(S)-(tetrahydrofuran-2-yl)methoxy]-quinazoline    4-[(3-ethynyl-phenyl)amino]-6,7-bis-(2-methoxy-ethoxy)-quinazoline    4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(morpholin-4-yl)-propyloxy]-6-[(vinyl-carbonyl)amino]-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-{[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]amino}-6-(5-{[(2-methanesulphonyl-ethyl)amino]methyl}-furan-2-yl)quinazoline    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-chloro-4-fluorophenyl)amino]-6-({4-[N,N-bis-(2-methoxy-ethyl)-amino]-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-(2,2-dimethyl-6-oxo-morpholin-4-yl)-ethoxy]-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-[2-(2,2-dimethyl-6-oxo-morpholin-4-yl)-ethoxy]-7-[(R)-(tetrahydrofuran-2-yl)methoxy]-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-7-[2-(2,2-dimethyl-6-oxo-morpholin-4-yl)-ethoxy]-6-[(S)-(tetrahydrofuran-2-yl)methoxy]-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-[1-(tert.-butyloxycarbonyl)-piperidin-4-yloxy]-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-methyl-piperidin-4-yloxy)-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yl-oxy}-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(methoxymethyl)carbonyl]-piperidin-4-yl-oxy}-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-((S)-tetrahydrofuran-3-yloxy)-7-hydroxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-(2-methoxy-ethoxy)-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-{trans-4-[(dimethylamino)sulphonylamino]-cyclohexan-1-yloxy}-7-methoxy-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-{trans-4-[(morpholin-4-yl)sulphonylamino]-cyclohexan-1-yloxy}-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-(2-acetylamino-ethoxy)-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-(2-methanesulphonylamino-ethoxy)-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-(1-aminocarbonylmethyl-piperidin-4-yloxy)-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-(cis-4-{N-[(tetrahydropyran-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-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-(cis-4-{N-[(morpholin-4-yl)sulphonyl]-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-ethoxy-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-chloro-4-fluoro-phenyl)amino]-6-(cis-4-acetylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline    4-[(3-ethynyl-phenyl)amino]-6-[1-(tert.-butyloxycarbonyl)-piperidin-4-yloxy]-7-methoxy-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-{N-[(4-methyl-piperazin-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-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-(2-methoxy-ethoxy)-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-chloro-4-fluoro-phenyl)amino]-6-(1-isopropyloxycarbonyl-piperidin-4-yloxy)-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-(cis-4-methylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-{cis-4-[N-(2-methoxy-acetyl)-N-methyl-amino]-cyclohexan-1-yloxy}-7-methoxy-quinazoline    4-[(3-ethynyl-phenyl)amino]-6-(piperidin-4-yloxy)-7-methoxy-quinazoline    4-[(3-ethynyl-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-methoxy-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-[(cis-2,6-dimethyl-morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(2-methyl-morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(S,S)-(2-oxa-5-aza-bicyclo[2,2,1]hept-5-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-{1-[(2-methoxyethyl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline    4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(3-methoxypropyl-amino)-carbonyl]-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-quinazolineoptionally in the form of the racemates, enantiomers, diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates or hydrates thereof. According to the invention these acid addition salts are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.
The dopamine agonists used are preferably compounds selected from among bromocriptin, cabergoline, alpha-dihydroergocryptine, lisuride, pergolide, pramipexol, roxindol, ropinirol, talipexol, tergurid and viozan, optionally in the form of the racemates, enantiomers, diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates or hydrates thereof. According to the invention these acid addition salts are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.
H1-Antihistamines which may be used are preferably compounds selected from among epinastine, cetirizine, azelastine, fexofenadine, levocabastine, loratadine, mizolastine, ketotifen, emedastine, dimetindene, clemastine, bamipine, cexchlorpheniramine, pheniramine, doxylamine, chlorophenoxamine, dimenhydrinate, diphenhydramine, promethazine, ebastine, desloratidine and meclozine, optionally in the form of the racemates, enantiomers, diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates or hydrates thereof. According to the invention these acid addition salts are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.
In addition, inhalable macromolecules may be used as disclosed in EP 1 003 478.
In addition, the compound may from the group of the derivatives of ergot alkaloids, triptanes, CGRP-inhibitors, phosphodiesterase-V inhibitors, optionally in the form of the racemates, enantiomers or diastereomers thereof, optionally in the form of the pharmacologically acceptable acid addition salts, solvates and/or hydrates thereof. Examples of ergot alkaloid derivatives are: dihydroergotamine, ergotamine.
Examples of substances suitable for inhalation include medicaments, medicament formulations and mixtures containing the above-mentioned active substances, and the salts and esters thereof and combinations of these active substances, salts and esters.
The invention is hereinafter described in more detail by means of examples. In the drawings:

Medicament dispensing device, medicament magazine therefor and method of removing a medicament from a medicament chamber


The present invention relates to a method and also an imaging system to compensate for patient motion when recording a series of images in medical imaging, in which a number of images of an area under examination of a patient (17) are recorded at intervals with an imaging system (1) and are related to one another. With the method a localization system (2) is used as the series of images are being recorded to permanently or at a time close to the recording of the individual images, record a momentary spatial location of the area under examination in a reference system permanently linked to the imaging system (1), a first spatial location of the area under examination recorded close to the time of recording of a first image is stored, and a deviation of the images recorded momentarily in each case of the first spatial location is determined and by changing the geometrical circumstances of the imaging system (1) at a time to close the recording of the spatial location and/or through geometrical adaptation of an image content of an image just recorded, is at least approximately commentated for, so that the images show the area under examination in the same position and orientation. The method does not require any time-consuming interaction with the operator and is also suitable for compensating for larger movements of the patient.

In a main area of application of the present method, the area of digital subtraction angiography, blood vessels of the human body are recorded with an imaging system, in this case an X-ray system, and displayed. With this method series of X-ray images of the area under examination of interest for the patient are recorded while a contrast means is injected to highlight the vessels (filling images). Furthermore an image of the area under investigation is recorded without injecting a contrast means (mask image). By digitally subtracting the mask image from the relevant filling images, subtraction images are obtained on which only the vessels are visible while overlays from other X-ray-absorbing structures, such as for example bones, disappear because of the subtraction.
The subtraction of the images however requires these images to be recorded under the same geometrical conditions so that they cover the same area. As a result of motion of the recorded structures between the individual recordings the result can be disruptive motion artifacts in the subtracted images. These can be caused by the patient moving between the recording of the mask image and the recordings of the filling images. A consequence of these movements can be that the resulting subtraction image can no longer be used for the diagnosis. Thus it can occur in practice that, because of these types of motion artifacts, disrupted subtraction images have to be repeated. This often involves additional effort in time and contrast means as well as exposing the patient to additional radiation.
A method known as roadmapping is a technique associated with digital subtraction angiography. This technique is applied for selective categorization of vessels in interventional therapy. With such vessels the current position of an X-ray-absorbing catheter is shown by X-ray fluoroscopy in a two-dimensional image. To also enable the blood vessel to be recognized as what is known as a roadmap an image is recorded at the start of the intervention for which a small amount of contrast means has been injected. This image is retained as a mask image. The following fluoroscopy images obtained without injection of a contrast means are subtracted from the mask image in each case. In this way subtraction images are obtained on which the catheter is visible as a bright object against the dark blood vessel and the background has been eliminated by subtraction.
Like digital subtraction angiography, roadmapping is also disrupted in the same way by motion of the imaged structures during recording of a series of images. For motion between the recording of the mask image and the relevant fluoroscopy image two problems arise here however. One is that the back-ground is no longer correctly subtracted so that image artifacts occur. The other is that it can occur that the position determined by the image of the catheter relative to the blood vessel shown is not correct. This serious error can for example result in the image showing a catheter outside the vessel although it is actually located inside the vessel. In an extreme case such incorrect representations can lead to errors in catheter control and result in injuries to the vessel. If the patient moves during the intervention it is therefore frequently necessary for the roadmap to be refreshed by recording a new mask image. This requires additional time and uses up more contrast means and is associated with a higher dose of radiation for the patient.
Different solutions are currently known for avoiding or for reducing this problem. The following three types of approach to solutions can thus be identified.
Patient-linked solutions aim to avoid movement of the patient during image recording. Thus for example, during thorax examinations, the patient can be trained to hold their breath while the series of images is being recorded. A further option is to avoid a number of sources of motion artifacts by full anesthetic. A disadvantage of patient-linked methods lies in the fact that they are only partly effective or can-not always be used. A full anesthetic for example involves many risks and is thus not medically advised for many applications of digital subtraction angiography. In addition, even with a full anesthetic, a number of sources of motion artifacts, such as breath movement, are still present.
For the solutions which are linked to how the images are recorded the image recording is executed so that motion artifacts are minimized. Previously the main method known in this area has been the Gating method in which the recording is coupled with a physiological measurement. Thus for example with ECG Gating images of only acquired in a particular heart phase, to compensate for heart movements. Gating methods are however only usable for a few specific applications and can only avoid motion artifacts caused by specific sources for which physiological signals can be measured.
A further approach to a solution for avoiding motion artifacts consists of retrospective image processing of the recorded images. With these techniques the aim is to use image processing to obtain a better match between mask image and filling image. The simplest technique used is known as pixel shifting or subpixel shifting, in which the user shifts the mask image in relation to the filling image manually in two dimensions until a minimization of the motion artifacts is obtained in the subtraction image. This method is implemented in all commercial angiography systems. Automatic methods which define the best match on the basis of quantifiable similarity measures are present in a few commercial angiography systems. More complex methods do not use global pixel shifting over the entire area of the image but optimize local areas of the image separately from one another, as described for example in U.S. Pat. No. 4,870,692 A. Furthermore scientific literature proposes numerous more expensive methods for movement correction. These essentially involve optimization methods in which attempts are made to find the transformation between masking image and a filling image which results in the fewest motion artifacts. Further examples of retrospective image processing can be found in the publications "Motion compensated digital subtraction angiography", M. Hemmendorff et al., SPIE '99, San Diego USA, Proceedings of play International Symposium on Medical Imaging 1999, Volume 3661, Image Processing, February 1999; Meijering E. H. et al., "Reduction of patient motion artifacts in digital subtraction angiography: evaluation of a fast and fully automatic technique", Radiology, 2001 April; 219(1): 288-293; or "Retrospective Motion Correction in Digital Subtraction Angiography: A Review", Erik H. W. Meijering et al., IEEE Transactions on Medical Imaging, Vol. 18, No. 1, January 1999, pp. 2-21.

Method and medical imaging system for compensating for patient motion


One embodiment of a non-precious metal catalyst for treating an exhaust gas stream comprises an alkali metal oxide component comprising lithium oxide, in combination with an alkaline earth support component, wherein the alkaline earth support component is an alkaline earth zeolite catalyst, an alkaline earth alumina catalyst, or a mixture thereof. Another embodiment of a non-precious metal catalyst for treating an exhaust gas stream comprises a substrate supporting a coating having more than about 6 weight percent of a lithium oxide component in combination with less than about 49 weight percent of an barium zeolite catalyst component and less than about 42 weight percent of a barium alumina catalyst component and not more than about 7 weight percent of a ceramic oxide binder.

The present invention relates to a catalyst for purifying exhaust gases from an internal combustion engine. In particular, it relates to a lean NOx catalyst.
It is well known in the art to use catalyst compositions, including those commonly referred to as three-way conversion (xe2x80x9cTWCxe2x80x9d) catalysts to treat the exhaust gases of internal combustion engines. Such catalysts, containing precious metals like platinum, palladium, and rhodium, have been found both to successfully promote the oxidation of unburned hydrocarbons (HC) and carbon monoxide (CO) and to promote the reduction of nitrogen oxides (NOx) in exhaust gas, provided that the engine is operated around balanced stoichiometry for combustion (xe2x80x9ccombustion stoichiometryxe2x80x9d; i.e., between about 14.7 and 14.4 air/fuel (A/F) ratio).
However, fuel economy and global carbon dioxide (CO2) emissions have made it desirable to operate engines under lean-burn conditions, where the air-to-fuel ratio is somewhat greater than combustion stoichiometry to realize a benefit in fuel economy. Diesel and lean-burn gasoline engines generally operate under highly oxidizing conditions (i.e., using much more air than is necessary to burn the fuel), typically at air/fuel ratios greater than 14.7 and generally between 19 and 35 Under these highly lean conditions, typical three-way catalysts exhibit little activity toward NOx reduction, as their reduction activity is suppressed by the presence of excess oxygen.
The control of NOx emissions from vehicles is a worldwide environmental problem. Lean-bum, high air-to-fuel ratio, and diesel engines are certain to become more important in meeting the mandated fuel economy requirements of next-generation vehicles. Development of an effective and durable catalyst for controlling NOx emissions under net oxidizing conditions accordingly is critical.
Recently, copper-ion exchanged zeolite catalysts have been shown to be active for selective reduction of NOx by hydrocarbons in the presence of excess oxygen. Platinum-ion exchanged zeolite catalyst is also known to be active for NOx reduction by hydrocarbons under lean conditions. However, this catalytic activity is significant only in a narrow temperature range around the lightoff temperature of hydrocarbon oxidation. All the known lean-NOx catalysts reported in the literature tend to lose their catalytic activity for NOx reduction when the catalyst temperature reaches well above the lightoff temperature of hydrocarbon oxidation. This narrow temperature window of the lean-NOx catalysts is considered to be one of the major technical obstacles, because it makes practical application of these catalysts difficult for lean-burn gasoline or diesel engines.). As an example, the Cu-zeolite catalysts deactivate irreversibly if a certain temperature is exceeded. Catalyst deactivation is accelerated by the presence of water vapor in the stream and water vapor suppresses the NO reduction activity even at lower temperatures. Also, sulfate formation at active catalyst sites and on catalyst support materials causes deactivation. Practical lean-NOx catalysts must overcome all three problems simultaneously before they can be considered for commercial use. In the case of sulfur poisoning, some gasoline can contain up to 1200 ppm of organo-sulfur compounds. Lean-NOx catalysts promote the conversion of such compounds to SO2 and SO3 during combustion. Such SO2 will adsorb onto the precious metal sites at temperatures below 300xc2x0 C. and thereby inhibits the catalytic conversions of CO, CxHy (hydrocarbons) and NOx. At higher temperatures with an Al2O3 catalyst carrier, SO2 is converted to SO3 to form a large-volume, low-density material, Al2(SO4)3, that alters the catalyst surface area and leads to deactivation. In the prior art, the primary solution to this problem has been to use fuels with low sulfur contents.
Another alternative is to use catalysts that selectively reduce NOx in the presence of a co-reductant, e.g., selective catalytic reduction (SCR) using ammonia or urea as a co-reductant. Selective catalytic reduction is based on the reaction of NO with hydrocarbon species activated on the catalyst surface and the subsequent reduction of NOx to N2. More than fifty such SCR catalysts are conventionally known to exist. These include a wide assortment of catalysts, some containing base metals or precious metals that provide high activity. Unfortunately, just solving the problem of catalyst activity in an oxygen-rich environment is not enough for practical applications. Like most heterogeneous catalytic processes, the SCR process is susceptible to chemical and/or thermal deactivation. Many lean-NOx catalysts are too susceptible to high temperatures, water vapor and sulfur poisoning (from SOx).
Yet another viable alternative involves using co-existing hydrocarbons in the exhaust of mobile lean-bum gasoline engines as a co-reductant and is a more practical, cost-effective, and environmentally sound approach. The search for effective and durable non-selective catalytic reduction xe2x80x9cNSCRxe2x80x9d catalysts that work with hydrocarbon co-reductant in oxygen-rich environments is a high-priority issue in emissions control and the subject of intense investigations by automobile and catalyst companies, and universities, throughout the world.
A leading catalytic technology for removal of NOx from lean-burn engine exhausts involves NOx storage reduction catalysis, commonly called the xe2x80x9clean-NOx trapxe2x80x9d. The lean-NOx trap technology can involve the catalytic oxidation of NO to NO2 by catalytic metal components effective for such oxidation, such as precious metals. However, in the lean NOx trap, the formation of NO2 is followed by the formation of a nitrate when the NO2 is adsorbed onto the catalyst surface. The NO2 is thus xe2x80x9ctrappedxe2x80x9d, i.e., stored, on the catalyst surface in the nitrate form and subsequently decomposed by periodically operating the system under stoichiometrically fuel-rich combustion conditions that effect a reduction of the released NOx (nitrate) to N2.
The lean-NOx-trap technology has been limited to use for low sulfur fuels because catalysts that are active for converting NO to NO2 are also active in converting SO2 to SO3. Lean NOx trap catalysts have shown serious deactivation in the presence of SOx because, under oxygen-rich conditions, SOx adsorbs more strongly on NO2 adsorption sites than NO2, and the adsorbed SOx does not desorb altogether even under fuel-rich conditions. Such presence of SO3 leads to the formation of sulfuric acid and sulfates that increase the particulates in the exhaust and poison the active sites on the catalyst. Attempts with limited success to solve such a problem have encompassed the use of selective SOx adsorbents upstream of lean NOx trap adsorbents. Furthermore, catalytic oxidation of NO to NO2 is limited in its temperature range. Oxidation of NO to NO2 by a conventional Pt-based catalyst maximizes at about 250xc2x0 C. and loses its efficiency below about 100 degrees and above about 400 degrees. Thus, the search continues in the development of systems that improve lean NOx trap technology with respect to temperature and sulfur considerations.
Another NOx removal technique comprises a non-thermal plasma gas treatment of NO to produce NO2 which is then combined with catalytic storage reduction treatment, e.g., a lean NOx trap, to enhance NOx reduction in oxygen-rich vehicle engine exhausts. In the lean NOx trap, the NO2 from the plasma treatment is adsorbed on a nitrate-forming material, such as an alkali material, and stored as a nitrate. An engine controller periodically runs a brief fuel-rich condition to provide hydrocarbons for a reaction that decomposes the stored nitrate into benign products such as N2. By using a plasma, the lean NOx trap catalyst can be implemented with known NOx absorbers, and the catalyst may contain less or essentially no precious metals, such as Pt, Pd and Rh, for reduction of the nitrate to N2. Accordingly, an advantage is that a method for NOx emission reduction is provided that is inexpensive and reliable. The plasma-assisted lean NOx trap can allow the life of precious metal lean NOx trap catalysts to be extended for relatively inexpensive compliance to NOx emission reduction laws. Furthermore, not only does the plasma-assisted lean NOx trap process improve the activity, durability, and temperature window of lean NOx trap catalysts, but it allows the combustion of fuels containing relatively high sulfur contents with a concomitant reduction of NOx, particularly in an oxygen-rich vehicular environment.
What is needed in the art is an exhaust gas catalyst system having improved durability, as well as effective NOx management, over extended operating time. The present invention overcomes many of the shortcomings of the prior art.
Alkali metal oxides, such as lithium oxide, generally are not very good catalysts for NOx treatment, and, additionally, are very susceptible to sulfate poisoning. Alkaline earth oxides, such as barium oxide, generally are good NOx catalysts, but, they also are susceptible to sulfate poisoning. However, alkali metal sulfates generally have a low temperature of decomposition. In particular, lithium sulfate, of all the alkali or alkaline earth sulfates, has the lowest temperature of decomposition. Lithium sulfate formed on a catalyst bed decomposes at xcx9c800xc2x0 C. in an oxidizing atmosphere. In contrast, barium sulfate, of all the alkali or alkaline earth sulfates, has the highest temperature of decomposition, at about 1600xc2x0 C. in an oxidizing atmosphere.
Some lean burn applications, such as diesel engines, are never xe2x80x9crichxe2x80x9d. An always lean system cannot generate an exotherm from hydrocarbon combustion and seldom exceeds about 800xc2x0 C. on a catalyst bed. Alkaline earth sulfates, and even most alkali metal sulfates, accordingly would not typically be expected to ever decompose once formed on an always lean system. Nevertheless, lithium sulfates may decompose even at the temperatures achievable on an always lean system.
According to the present invention, an alkali metal oxide is included into the catalyst formulation of a NOx occluding catalyst. The alkali metal oxide provides a preferential scavenger for sulfates deposited on the catalyst surface. The alkali metal sulfate can be decomposed during high temperature excursions. The alkali metal sulfate sulfate decomposes to lithium oxide and sulfur is released to the exhaust stream as SO2. In this manner, irreversible sulfation of the active NOx agent and ozone agent is thereby prevented.
The above-described and other features and advantages of the present invention will be appreciated and understood by those skilled in the art from the following detailed description, and appended claims.
The catalyst generally comprises a calcined coating of an alkali metal oxide and an alkaline earth/support oxide coated onto a chemically stable and thermally insulating substrate, typically such as cordierite, mullite, and the like. The support oxide generally may be a zeolite or an aluminum oxide or a mixture of zeolite and aluminum oxide. Preferably, the catalyst coating also includes a ceramic oxide binder and/or stabilizer.
The alkali metal oxide catalyst component may comprise any alkali metal. Preferably, the alkali metal oxide catalyst component comprises an alkali metal selected from the group consisting of potassium, sodium, lithium, and mixtures thereof. Sodium and lithium and mixtures thereof are more preferred; lithium is particularly preferred.
Suitable lithium compounds for introduction of the alkali metal component include lithium formate, lithium citrate, lithium acetate, lithium oxylate, lithium nitrate, lithium carbonate, lithium hydroxide and lithium oxide. Lithium acetate, lithium oxylate, and lithium formate are preferred. Lithium formate is particularly preferred.
Suitable sodium compounds for introduction of the alkali metal component include sodium formate, sodium citrate, sodium acetate, sodium oxylate, sodium nitrate, sodium carbonate, sodium hydroxide and sodium oxide. Sodium acetate, sodium oxylate, and sodium formate are preferred. Sodium formate is particularly preferred.
Suitable potassium compounds for introduction of the alkali metal component include potassium formate, potassium citrate, potassium acetate, potassium oxylate, potassium nitrate, potassium carbonate, potassium hydroxide and potassium oxide. Potassium acetate, potassium oxylate, and potassium formate are preferred. Potassium formate is particularly preferred.
The alkaline earth/support catalyst component preferably is not more than about 95 wt % of the total catalyst, and more preferred at not more than about 90 wt %. Particularly preferred is alkaline earth/support component at about 85 wt %. Preferably, the alkali metal oxide catalyst component is at least about 4 wt % and more preferred at least about 8 wt %. Particularly preferred is alkali metal oxide at about 12 wt %. The ceramic binder preferably is greater than about 1 wt % and not more than about 7 wt %; about 3 wt % is particularly preferred.
A preferred calcined catalyst coating comprises less than about 49 wt % alkaline earth/zeolite, less than about 42 wt % alkaline earth/aluminum oxide, more than about 6 wt % alkali metal oxide and not more than about 7 wt % ceramic oxide binder. A more preferred calcined coating comprises less than about 48 wt % alkaline earth/zeolite, less than about 41 wt % alkaline earth/aluminum oxide, more than about 8 wt % alkali metal oxide, and not more than about 5 wt % ceramic oxide binder. A particularly preferred calcined coating comprises about 47 wt % alkaline earth/zeolite, about 40 wt % alkaline earth/aluminum oxide, about 10 wt % alkali metal oxide and about 3 wt % ceramic oxide binder.
The surface area of the alkali metal oxides may be stabilized with other binder oxides, such as oxides of silicon, titanium, and/or zirconium. Titanium and zirconium are preferred; zirconium is particularly preferred. The binder/stabilizer preferably comprises not more than about 7 wt %; more preferred at not more than about 5 wt %; and, particularly preferred not more than about 3 wt %.
Suitable zirconium compounds for introduction of the surface area stabilizer include zirconium acetylacetonate, zirconium n-butoxide, zirconium nitrate, zirconium tetraamine nitrate, zirconium tetraamine citrate, zirconium 2-ethylhexanoate, and zirconium isopropoxide. Zirconium tetraamine citrate, zirconium butoxide, and zirconium isopropoxide are preferred; zirconium butoxide and zirconium isopropoxide are more preferred; and, zirconium isopropoxide is particularly preferred.
Suitable titanium compounds for introduction of the surface area stabilizer include titanium oxylate, titanium ethoxide, titanium methoxide, titanium isopropoxide, zirconium n-butoxide. Titanium butoxide, titanium ethoxide, and titanium isopropoxide are preferred; titanium ethoxide and titanium isopropoxide are more preferred; and, titanium isopropoxide is particularly preferred.
Suitable silicon compounds for introduction of the surface area stabilizer include silicon acetate, tetraethoxysilane, tetramethoxysilane, vinyltrimethoxysilane, ureidopropyltriethoxysilane and aminopropylsilanetriol. Tetraethoxysilane, silicon acetate, and tetramethoxysilane are preferred; silicon acetate and tetramethoxysilane are more preferred; and, tetramethoxysilane is particularly preferred.
The catalyst of the present invention comprises an alkaline earth/support component, wherein the support may be a zeolite and/or alumina. The alumina fraction of the support may be present in a proportion ranging from about 0 wt % to about 100 wt % of the alkaline earth/support fraction. A particularly preferred admixture comprises an alkaline earth/aluminum oxide fraction in a proportion ranging from about 35 wt % to about 45 wt %, and an alkaline earth/zeolite fraction in a proportion ranging from about 55 wt % to about 65 wt %.
Any type zeolite may be used; preferred zeolites include X type zeolite, Y type zeolite, and/or ZSM-5 type zeolite. A ZSM-5 zeolite with pores 4-5 A (angstroms) is preferred and an X zeolite is more preferred and a Y-type zeolite with pores 7-8 A is greatly preferred. A zeolite surface area of at least about 300 m2/gram is preferred, at least about 400 m2/g is more preferred, and a surface area of at least about 500 m2/g is particularly preferred. The preferred zeolite average particle size is less than about 0.9 microns; more preferred are zeolite particles of an average size less than about 0.6 microns; and particularly preferred are zeolites having an average particle size less than about 0.3 microns. The zeolite particles preferably feature average pore sizes ranging from about 4 to about 10 angstroms (xe2x80x9cAxe2x80x9d), with average pore sizes ranging from about 7 to 8 A particularly preferred. Preferably, the zeolite has a Na2O content of at least about 3 wt %; a content of at least about 8 wt % is more preferred; and a content of at least about 13 wt % is particularly preferred.
The aluminum oxide particles providing the matrix comprise agglomerations of small psuedocrystalline alumina particles typically of about 0.3 microns or less. The agglomerations preferably are larger than about 10 microns and less than about 30 microns. The alumina matrix is mixed with a Ba-zeolite catalyst component, typically featuring a particulate size of about 0.3 microns. In general, the smaller the zeolite particle, the more hydrothermally stable the zeolite becomes, thereby improving its long-term activity. Pursuant to the invention, the zeolite active catalysts preferably are dispersed throughout the alumina matrix.
Preferably, the alumina has a surface area of at least about 150 m2/gram; a surface area of at least about 200 m2/g is more preferred; and, a surface area of at least about 250 m2/g is particularly preferred. An average alumina pore size of at least about 40 A is preferred; a pore size of at least about 60 A is more preferred; and, a pore size of at least about 80 A is particularly preferred. Specific acidity ranging from about 50 moles (millimoles) n-butylamine/m2xc3x9710xe2x88x924 to about 500 mmoles n-butylamine/m2xc3x9710xe2x88x924 is preferred; a specific acidity of about 350 mmoles n-butlyamine/m2xc3x9710xe2x88x924 is particularly preferred.
The zeolite catalyst component preferably comprises an alkaline earth content of about 18 wt % to about 36 wt %; about 24 wt % to about 30 wt % is particularly preferred. The aluminum oxide catalyst component preferably comprises an alkaline earth content of about 18 wt % to about 36 wt %; about 24 wt % to about 30 wt % is particularly preferred.
Any alkaline earth element may be used as the active catalyst. For example, the active catalyst element may comprise calcium, strontium, and/or barium. The use of barium is particularly preferred. Tests have indicated that calcium-doped catalysts generally convert about 30% NOx to N2; strontium-doped catalysts generally convert about 50% NOx to N2; barium-doped catalysts generally convert about 70% NOx to N2. Based on a desire in the industry to optimize conversion of NOx to N2 at about 90% or better, barium is the particularly preferred occluding catalyst material.
Accordingly, Ba is the preferred occluding catalyst for both the zeolite and the alumina components of the present catalyst. The alumina matrix features enhanced trapping efficiency if it is doped with a material such as barium. In specific, nitrogen species can neutralize catalytically active sites. Barium is the most robust alkaline earth element for resistance to nitrogen poisoning. The alumina matrix provides sacrificial sites for nitrogen poisoning, thus precluding large polycyclic nitrogen compounds from entering and poisoning the small pores of the zeolite catalyst component. The zeolite catalyst component preferably comprises a barium content of about 18 wt % to about 3,6 wt %; about 24 wt % to about 30 wt % is particularly preferred. The alumina matrix catalyst component preferably has a barium content of at least about 14 wt %; at least about 21 wt % is more preferred; and, at least about 28 wt % is particularly preferred. Exhaust deposits of oil derived xe2x80x9cglassyxe2x80x9d compounds such as calcium phosphate and zinc phosphate can greatly reduce diffusion. High levels of alkaline earths, such as barium, prevent formation of these diffusion limiting barriers.
Suitable barium sources for preparation of a barium-alumina component include barium nitrate, barium acetate, barium hydroxide, barium ethoxide, barium isopropoxide, and/or barium 2-ethylhexanoate. Barium acetate, barium isopropoxide, and barium 2-ethylhexanoate are preferred. Barium 2-ethylhexanoate is particularly preferred.
The following examples are provided to further describe the invention. The examples are intended to be illustrative in nature and are not to be construed as limiting the scope of the invention.

Alkali metal/alkaline earth lean NOx catalyst


The present invention relates to a two-compartment aerosol device containing a hair treatment composition in a first compartment and a compressed gas chosen from air, nitrogen and carbon dioxide, and mixtures thereof, in a second compartment, where the hair treatment composition contains, in an alcoholic or aqueous-alcoholic cosmetically acceptable medium, at least one hair sheen agent and/or conditioner in a concentration of greater than 0.4% by weight relative to the total weight of the composition.

The present invention relates to a two-compartment aerosol device comprising a hair treatment composition and a particular compressed gas, and to a hair treatment process.
Hair treatment compositions, packaged in aerosol spray form, generally contain a liquid phase comprising, in an alcoholic or, less commonly, aqueous-alcoholic cosmetically acceptable medium, a hair treatment agent, for example an agent for giving the hair sheen and/or a hair conditioner, and a propellant, which is a liquefied gas under reduced pressure or dissolved in the liquid phase.
Other aerosol devices comprising such a liquid phase exist, but they comprise compressed gases for propelling the liquid phase. However, these compressed-gas devices have the drawback of losing gas pressure over time. Specifically, it is observed that the compressed gases leak out over time or during poor use of the container, i.e. when it is held upside down.
This drawback results in poor propulsion of the liquid phase and, consequently, poor distribution of the liquid phase on the hair.
The Applicant has made the surprising discovery that mechanical separation of the alcoholic or aqueous-alcoholic liquid phase from the propellent compressed gas makes it possible to solve these problems of leakage and of distribution of the liquid phase on the hair. In addition, the use of a two-compartment aerosol device with a particular compressed gas makes it possible to obtain a gentle and broad spray, which ensures improved distribution of the liquid phase on the hair, disturbs the hairstyle less and maintains the shape of the said hairstyle.
One subject of the invention is thus a two-compartment aerosol device comprising a hair treatment composition and a compressed gas as described below.
Another subject of the present invention consists of a hair treatment process.
Other subjects, characteristics, aspects and advantages of the invention will emerge even more clearly on reading the description and the various examples that follow.
The two-compartment aerosol device according to the invention comprises:                (a) a hair treatment composition comprising, in an alcoholic or aqueous-alcoholic cosmetically acceptable medium, at least one hair sheen agent and/or conditioner in a concentration of greater than 0.4% by weight relative to the total weight of the composition, in a first compartment, and        (b) a compressed gas chosen from air, nitrogen and carbon dioxide, and mixtures thereof, in a second compartment, air being particularly preferred.
The said compressed gas is preferably used at a pressure of between 1 and 12 bar and better still between 9 and 11 bar.
For the purposes of the present invention, the term "sheen agent" means any compound capable of giving the hair sheen greater than that of the hair before treatment. This sheen characteristic may be evaluated in a sensory manner or by means of suitable technical devices, for instance photogoniometers.
For the purposes of the present invention, the term "conditioner" means any compound capable of improving at least one of the cosmetic properties of the hair, such as its disentangling, softness, body or smoothness.
The hair sheen agent and/or conditioner used in the context of the present invention is chosen especially from silicones, fatty substances or other non-silicone agents known for their conditioning or sheen-providing properties, and mixtures thereof.
It is especially possible to use in the context of the present invention non-volatile silicone oils such as polydimethylsiloxanes (PDMS), phenylated polyorganosiloxanes such as phenyltrimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenylmethyldimethyltrisiloxanes, diphenyldimethicones, phenyldimethicones and polymethylphenylsiloxanes, which may be fluorinated; polysiloxanes modified with fatty acids, with fatty alcohols or with polyoxyalkylenes, fluorosilicones and perfluorinated silicone oils, and mixtures thereof.
Among the preferred non-volatile silicone oils that may be mentioned are polydimethylsiloxanes, polymethylphenylsiloxanes, silicones comprising polyoxyalkylene blocks or grafts, in particular polyoxyethylene or copoly (oxyethylene/oxypropylene) blocks or grafts such as dimethicone copolyols, silicones comprising both hydrocarbon-based hydrophobic groups (for example C2–C30 alkyl groups) and polyoxyethylenated or copoly (oxyethylenated/oxypropylenated) blocks or grafts such as alkyldimethicone copolyols, silicones bearing fluoro or perfluoro groups such as perfluoroalkyl polydimethylsiloxanes and perfluoroalkyl polymethylphenylsiloxanes, and mixtures thereof.
These oils may be silicone oils optionally comprising alkyl or alkoxy groups at the end of the silicone chain or pendant thereon.
As volatile silicone oils that may be used in the invention, mention may be made of linear or cyclic silicones, preferably with a viscosity at room temperature and at atmospheric pressure of less than 8 mm2/s (8 cSt), and in particular comprising from 2 to 7 silicon atoms. Mention may be made especially of octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, hexadecamethylcyclohexasiloxane, heptamethylhexyltrisiloxane and heptamethyloctyltrisiloxane, and mixtures thereof.
Hydrocarbon-based oils may also be used in the context of the present invention as sheen agents and/or conditioners.
The term "hydrocarbon-based oil" means an oil predominantly containing carbon and hydrogen atoms and especially alkyl or alkenyl chains, for instance alkanes or alkenes, but also an oil containing, in addition to hydrogen and carbon atoms, oxygen atoms in the form of an ether, ester, alcohol or carboxylic acid function.
Mention may thus be made of hydrocarbon-based oils such as liquid paraffin or liquid petroleum jelly, mink oil, turtle oil, soybean oil, perhydrosqualene, sweet almond oil, beauty-leaf oil, palm oil, grapeseed oil, sesame oil, corn oil, parleam oil, arara oil, rapeseed oil, sunflower oil, cotton oil, apricot oil, castor oil, avocado oil, jojoba oil, olive oil or cereal germ oil; esters of lanolic acid, of oleic acid, of lauric acid and of stearic acid, fatty esters, such as isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, diisopropyl adipate, isononyl isononanoate, 2-ethyhexyl palmitate, 2-hexyldecyl laurate, 2-octyldecyl palmitate, 2-octyldodecyl myristate or lactate, bis(2-ethylhexyl) succinate, diisostearyl malate, glyceryl triisostearate or diglyceryl triisostearate; higher fatty alcohols containing at least 12 carbon atoms, such as stearyl alcohol or oleyl alcohol, linoleyl alcohol linolenyl alcohol, isostearyl alcohol or octyldodecanol.
Waxes may also be used as sheen agents and/or conditioners. These waxes may be of natural origin (carnauba wax or candelilla wax) or of synthetic origin, such as silicone waxes, synthetic ceramides or natural ceramides.
Linear or branched fatty alcohols comprising from 10 to 30 carbon atoms may also be used as sheen agents and/or conditioners.
Among the sheen agents and/or conditioners mentioned above, the ones preferably used are phenylated polyorganosiloxanes, liquid petroleum jelly, isopropyl myristate and isopropyl palmitate, or mixtures thereof.
The said hair sheen agent and/or conditioner is preferably present in an amount of between 0.4% and 40% by weight and better still between 1% and 20 by weight, relative to the total weight of the hair treatment composition, limits included.
The term "cosmetically acceptable medium" means a medium that is compatible with the hair, but which also has a pleasant odour, appearance and feel.
The alcoholic or aqueous-alcoholic cosmetically acceptable medium comprises at least one alcohol such as a C1-4 alcohol, for example ethanol or isopropanol.
In an aqueous-alcoholic medium, the proportion of water may range between 1% and 95% and preferably between 15 and 90% of the total weight of the aerosol composition.
The hair treatment composition may also comprise additives such as nonionic, cationic, anionic or amphoteric fixing polymers, treating active agents, moisturizers such as glycerol, UV-screening agents, acids, bases, plasticizers, solubilizers, preserving agents, colorants, pigments, fragrances, vitamins, provitamins, nonionic, anionic, cationic or amphoteric surfactants and anticorrosion agents, and mixtures thereof.
A person skilled in the art will take care to select the optional additives and the amount thereof such that they do not harm the properties of the compositions of the present invention.
These additives are especially present in the composition according to the invention in an amount ranging from 0% to 20% by weight relative to the total weight of the composition.
Preferably, the two-compartment aerosol device consists of an outer aerosol can comprising an inner pocket hermetically welded to a valve. The composition is introduced into the inner pocket and a compressed gas is introduced between the pocket and the can at a pressure that is sufficient to eject the product in the form of a spray through the orifice of a nozzle. Such a device is sold under the name EP Spray by the company EP-Spray System SA.
The aerosol devices of the invention may preferably be hair lacquers.
The present invention also relates to a hair treatment process, which consists in vaporizing the hair treatment composition contained in the aerosol device according to the invention onto wet or dry hair, and leaving the hair to dry with or without supplying external heat.
The examples that follow are given as illustrations of the present invention.
In the examples that follow, all the amounts are indicated as weight percentages relative to the total weight of the composition, except where otherwise mentioned.

Aerosol device comprising a hair treatment composition, and hair treatment process