Abstract: An inhaler device (1) contains, or is capable of accepting, a plurality of doses of a medicament to be dispensed from the inhaler (1). To ameliorate the problem of double dosing from the inhaler (1), the device further comprises prevention means (26, 28, 40) for preventing, at least temporarily, the dispensing of a dose of medicament, and detection means (32) for detecting the inhalation of a previously dispensed dose of medicament. When the detection means (32) detects the inhalation of the previously dispensed dose of medicament, it releases the prevention means (26, 28, 40), allowing the device to dispense a further dose of medicament. The detection means (32) may be a pressure sensor, and the prevention means (26, 28, 40) may operate by causing a disengagement of an actuation mechanism.

Abstract: This invention is directed to a [di(ether or thioether)heteroaryl or fluoro substituted aryl] compound or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which is useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. The present invention is therefore directed to their pharmacological use for inhibiting TNF and/or cyclic AMP phosphodiesterase, pharmacological compositions comprising the compounds and methods for their preparation.

Abstract: A counter mechanism useable with a dry powder inhaler is disclosed. The mechanism features first and second indicator members rotatable about a central axis. The indicator members have counting indicia visible to indicate inhaler doses remaining or dispensed. A coupling transmits rotary motion from the inhaler to the second indicator member when the inhaler is charged with a dose. A slave wheel, rotatable about an axis offset from the central axis, has a drive transfer wheel on one face and a gear on an opposite face. The gear engages the second indicator member, the drive transfer wheel intermittently engages and rotates the first indicator member in response to rotary motion of the second indicator member.

Abstract: A counter mechanism useable with a dry powder inhaler is disclosed. The mechanism features first and second indicator members rotatable about a central axis. The indicator members have counting indicia visible to indicate inhaler doses remaining or dispensed. A coupling transmits rotary motion from the inhaler to the second indicator member when the inhaler is charged with a dose. A slave wheel, rotatable about an axis offset from the central axis, has a drive transfer wheel on one face and a gear on an opposite face. The gear engages the second indicator member, the drive transfer wheel intermittently engages and rotates the first indicator member in response to rotary motion of the second indicator member.

Abstract: A rotatably actuated counter is disclosed. The counter includes a ratchet driven unit wheel nested within a tens wheel. Each wheel has a radial face displaying counting indicia. The tens wheel is transparent, allowing the indicia on the unit wheel to be viewed adjacent to the indicia on the tens wheel to provide a total count. A slave wheel is positioned between the unit and tens wheels. A gear on one face of the slave wheel engages gear teeth on the tens wheel. A Geneva mechanism on the other face is engaged by a foot on the unit wheel once per rotation. The wheels are rotatably mounted within a housing having a sidewall with a window through which the count indicia may be viewed. The unit wheel rotates in ten increments and then rotates the tens wheel through one increment by engaging and rotating the slave wheel.

Abstract: This invention is directed to a [di(ether or thioether)heteroaryl or fluoro substituted aryl] compound or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which is useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. The present invention is therefore directed to their pharmacological use for inhibiting TNF and/or cyclic AMP phosphodiesterase, pharmacological compositions comprising the compounds and methods for their preparation.

Abstract: A counter mechanism useable with a dry powder inhaler is disclosed. The mechanism features first and second indicator members rotatable about a central axis. The indicator members have counting indicia visible to indicate inhaler doses remaining or dispensed. A coupling transmits rotary motion from the inhaler to the second indicator member when the inhaler is charged with a dose. A slave wheel, rotatable about an axis offset from the central axis, has a drive transfer wheel on one face and a gear on an opposite face. The gear engages the second indicator member, the drive transfer wheel intermittently engages and rotates the first indicator member in response to rotary motion of the second indicator member.

Abstract: A compound of formula XIX wherein R1, R2, Z1, Z2, Q1, Q2 and Q3 as defined in the specification.

Abstract: Compounds of formula (I) are described in which Het is a five or six membered heteroaromatic ring of the formula in which one of R1 and R2 is optionally substituted heteroaryl and the other is optionally substituted heteroaryl or optionally substituted aryl; X1 is a bond, X3 and X4 are each independently N or C and X2 and X5 are independently CH, N, NH, O or S; or X3 and X4 are C, one of X1, X2 and X5 is N and the others are N or CH; but excluding compounds in which X1 is a bond, one of X2 and X5 is N and the other is NH and X3 and X4 are both C; R3 represents a group -L1-R6; R4 represents hydrogen, alkyl or hydroxyalkyl; or R3 and R4, when attached to the same carbon atom, may form with the said carbon atom a cycloalkyl, cycloalkenyl or heterocycloalkyl ring or a group C?CH2; R5 represents hydrogen or alkyl; and m is zero or an integer 1 or 2; and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates of compounds of formula (I) and N-oxides thereof, and their prodrugs.

Abstract: A rotatably actuated counter is disclosed. The counter includes a ratchet driven unit wheel nested within a tens wheel. Each wheel has a radial face displaying counting indicia. The tens wheel is transparent, allowing the indicia on the unit wheel to be viewed adjacent to the indicia on the tens wheel to provide a total count. A slave wheel is positioned between the unit and tens wheels. A gear on one face of the slave wheel engages gear teeth on the tens wheel. A Geneva mechanism on the other face is engaged by a foot on the unit wheel once per rotation. The wheels are rotatably mounted within a housing having a sidewall with a window through which the count indicia may be viewed. The unit wheel rotates in ten increments and then rotates the tens wheel through one increment by engaging and rotating the slave wheel.

Abstract: This invention is directed to a [di(ether or thioether)heteroaryl or fluoro substituted aryl] compound or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which is useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. The present invention is therefore directed to their pharmacological use for inhibiting TNF and/or cyclic AMP phosphodiesterase, pharmacological compositions comprising the compounds and methods for their preparation.

Abstract: A counter mechanism useable with a dry powder inhaler is disclosed. The mechanism features first and second indicator members rotatable about a central axis. The indicator members have counting indicia visible to indicate inhaler doses remaining or dispensed. A coupling transmits rotary motion from the inhaler to the second indicator member when the inhaler is charged with a dose. A slave wheel, rotatable about an axis offset from the central axis, has a drive transfer wheel on one face and a gear on an opposite face. The gear engages the second indicator member, the drive transfer wheel intermittently engages and rotates the first indicator member in response to rotary motion of the second indicator member.

Abstract: This invention is directed to physiologically active compounds of formula (I) wherein represents a bicyclic ring system, of about 10 to about 13 ring members, in which the ring is an azaheterocycle, and the ring represents an azaheteroaryl ring, or an optionally halo substituted benzene ring; and N-oxides thereof, and pharmaceutically acceptable salts of the compounds of formula (I) and N-oxides thereof, Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmnaceutical compositions comprising compoundS of formula (I), their phatmaceUtical use and methods for their preparation.

Abstract: Provided herein are dry powder inhalers for the delivery of metered doses of medicament, counters associated with the inhalers for counting and displaying the number of doses administered or remaining within the inhaler, and methods of use thereof.

Abstract: Chemical compositions containing physiologically active compounds of general formula (I): wherein R1 is aryl or heteroaryl; R2 represents hydrogen, acyl, cyano, halo, lower alkenyl or lower alkyl optionally substituted by a substituent selected from cyano, heteroaryl, heterocycloalkyl, -Z1R8, —C(?O)—NY3Y4, —CO2R8, —NY3Y4, —N(R6)—C(?O)—R7, —N(R6)—C(?O)—NY3Y4, —N(R6)—C(?O)—OR7, —N(R6)—SO2—R7, —N(R6)—SO2—NY3Y4 and one or more halogen atoms; R3 represents hydrogen, aryl, cyano, halo, heteroaryl, lower alkyl, —C(?O)—OR5 or —C(?O)—NY3Y; and X1 represents N, CH, C-halo, C—CN, C—R7, C—NY3Y4, C—OH, C-Z2R7, C—C(?O)—OR5, C—C(?O)—NY3Y4, C—N(R8)—C(?O)—R7, C—SO2—NY3Y4, C—N(R8)—SO2—R7, C-alkenyl, C-alkynyl or C—NO2; and their prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their prodrugs, as well as to novel compounds within the scope of formula (I). Such compounds and compositions have valuable pharmaceutical properties, in particular the ability to inhibit protein kinases.

Abstract: The invention is directed to physiologically active compounds of formula (I): wherein: R1 represents optionally substituted aryl, optionally substituted heteroaryl, R3NH—Ar1—L2— or R3—NH—C(?O)—NH—Ar2—L2—; R3 represents aryl or heteroaryl; Ar1 represents a saturated, partially saturated or fully unsaturated 8- to 10-membered bicyclic ring system containing at least one heteroatom selected from O, S or N; Ar2 represents aryldiyl or heteroaryldiyl; L1 represents a linkage, such as an alkylene linkage; L2 represents an alkylene chain linkage; R2 represents hydrogen, halogen, C1-4alkyl or C1-4alkoxy; and Y is carboxy or an acid bioisostere; but excluding compounds where an oxygen, nitrogen or sulfur atom is attached directly to a carbon carbon multiple bond of an alkenylene or alkynylene residue; and the corresponding N-oxides and ester prodrugs thereof, and the pharmaceutically acceptable salts and solvates of such compounds, and the N-oxides and ester prodrugs thereof.

Abstract: The invention is directed to physiologically active compounds of general formula (I): wherein: represents (i) a saturated 3 to 6 membered carbocycle, optionally substituted by one or more alkyl groups, (ii) indanyl or (iii) a saturated 4 to 6 membered heterocyclic ring; R1 represents R3Z1-Het- or R4N(R5)—C(?O)—NH—Ar1—; L1 represents an —R6—R7— linkage; R2 represents hydrogen, halogen, lower alkyl or lower alkoxy; L2 represents an alkylene linkage; Y is carboxy or an acid bioisostere; and their corresponding N-oxides or prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their corresponding N-oxides or prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (?4?1).

Abstract: The invention relates to the use of an adsorbent and a sealed package, for example an overwrap, to protect a pharmaceutical product in a solid state in the presence of a reducing sugar.

Abstract: A method for maintaining the enclosed volume of a sealed package at about ambient pressure, wherein the package contains a pressurized container comprising a drug, and an HFA (hydrofluoroalkane) propellant selected from the group consisting of HFA 134a and HFA p227, or a mixture thereof; wherein the method comprises the steps of (1) positioning an effective amount of a HFA adsorbent material, and said pressurized container, within a sealable package; (2) sealing the package so that the pressurized container and adsorbent are in an enclosed volume within the package at a pressure equal to about ambient pressure; and (3) adsorbing any leakage of the HFA propellant into the HFA adsorbent material so as to maintain the enclosed volume at about ambient pressure.

Abstract: Provided herein is a stable pharmaceutical product comprising a dry powder inhalation device, and a pharmaceutical composition that comprises R,R-Formoterol L-tartrate salt, in particular crystalline R,R-formoterol L-tartrate; and ciclesonide.