Abstract

The present invention relates to a novel process for the synthesis of the intermediate compounds constituted by chromanyl haloketones of formula III and 6-fluoro-2-(oxiran-2-yl)chromans of formula I. The intermediates thus obtained can be used for the synthesis of Nebivolol.

IPC Classes  ?

• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4
• C07D 407/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond

Abstract

The present invention relates to a novel process for the synthesis of the intermediate compounds constituted by chromanyl haloketones of formula III and 6-fluoro-2-(oxiran-2-yl) chromans of formula I. The intermediates thus obtained can be used for the synthesis of Nebivolol.

IPC Classes  ?

• C07D 407/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4

Abstract

A device for the automatic injection of doses of a drug compound is described. The device has a sliding sheath which, when depressed with its front end against the injection site, interacts with cam means to activate triggering of a plunger, thus controlling delivery of a drug dose. Plunger guide means are provided for controlling the triggering sequence and means for arming the device in the dose delivery condition. Automatic needle re-sheathing and resetting of a lock-out condition after each dose is delivered are also provided.

IPC Classes  ?

• A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
• A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
• A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing

Abstract

A device for the automatic injection of doses of a drug is described. The device has a slide and cam means, a syringe unit with a piston, and guide means. The axial movement of the slide initiated by a user by depressing its front end against an injection site, causes an angular displacement of the cam means that, in cooperation with the guide means, controls movement of the syringe piston and therefore administration of a drug dose.

IPC Classes  ?

• A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
• A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
• A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
• A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
• A61M 5/31 - Syringes Details
• A61M 5/178 - Syringes

Abstract

The present invention relates to a novel process for the synthesis of the Nebivolol product depicted in Scheme 1, comprised of a reduced number of high-yield steps, and characterized by the enzymatic resolution of the chroman ester precursor.

IPC Classes  ?

• C12P 17/16 - Preparation of heterocyclic carbon compounds with only O, N, S, Se, or Te as ring hetero atoms containing two or more hetero rings
• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4

Abstract

The present invention relates to a novel process for the synthesis of Nebivolol product represented in Scheme (1), comprised of a reduced number of high-yield steps, and characterized by the kinetic resolution of the two epoxide pairs diastereoisomeric therebetween (mixture 1), allowing to avoid complex chromatographic separations.

IPC Classes  ?

• C07D 311/00 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings

Abstract

A device for the automatic injection of doses of a drug is disclosed, comprising a slide (30) and cam means (23, 28, 36), a syringe unit (6) with a piston (8), and guide means (26) thereof; the axial movement of the slide initiated by the user by depressing its front end against the injection site, causes the angular displacement of the cam means that, in cooperation with the guide means, controls the movement of the syringe piston and therefore the administration of a drug dose.

IPC Classes  ?

• A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
• A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
• A61M 5/31 - Syringes Details
• A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
• A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles

Abstract

A device for the automatic injection of doses of a drug compound comprising a sliding sheath (30) which, when depressed with its front end (3) against the injection site, interacts with cam means (26, 27, 28) to activate the triggering of a plunger (8), controlling the delivery of a drug dose. Plunger guide means (44) are provide for controlling the triggering sequence and means (4) for arming the device in the dose delivery condition. Automatic needle re-sheathing and resetting of a lock-out condition after each dose is delivered are provided. The number of the device components is reduced resulting in a simpler structure and cost reduction.

IPC Classes  ?

• A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
• A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
• A61M 5/31 - Syringes Details
• A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
• A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles

Abstract

A device for the automatic injection of doses of a drug is disclosed, comprising a slide (30) and cam means (23, 28, 36), a syringe unit (6) with a piston (8), and guide means (26) thereof; the axial movement of the slide initiated by the user by depressing its front end against the injection site, causes the angular displacement of the cam means that, in cooperation with the guide means, controls the movement of the syringe piston and therefore the administration of a drug dose.

IPC Classes  ?

• A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
• A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
• A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
• A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
• A61M 5/31 - Syringes Details

Abstract

A device for the automatic injection of doses of a drug compound comprising a sliding sheath (30) which, when depressed with its front end (3) against the injection site, interacts with cam means (26, 27, 28) to activate the triggering of a plunger (8), controlling the delivery of a drug dose. Plunger guide means (44) are provide for controlling the triggering sequence and means (4) for arming the device in the dose delivery condition. Automatic needle re-sheathing and resetting of a lock-out condition after each dose is delivered are provided. The number of the device components is reduced resulting in a simpler structure and cost reduction.

IPC Classes  ?

• A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
• A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
• A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
• A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
• A61M 5/31 - Syringes Details

Abstract

A two-dose autoinjector for a medicament wherein the locking and releasing of the drive spring of the autoinjector is controlled through stepped guides with ramps for two successive slidings of slides operated by the spring and connected with the syringe and plunger. The guides and the slides are pivotable relative to one another and the sliding direction, while the syringe can only slide axially. To enable or disable the sliding of the slides within the guides an angularly angularly mobile arming member is provided formed with a guide track substantially equal to that of the stationary member where the guides are formed.

IPC Classes  ?

• A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
• A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
• A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles

Abstract

The present invention relates to a novel process of synthesis of epoxides, 6-fluoro-2- (oxiran-2-yl) chroman (Figure 1), intermediates for the synthesis of nebivolol, depicted in Scheme (1), enabling to obtain the above- mentioned epoxides in a racemic or semichiral form.

IPC Classes  ?

• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4
• C07D 407/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond

Abstract

The present invention relates to a novel process for the synthesis of Nebivolol product represented in Scheme (1), comprised of a reduced number of high-yield steps, and characterized by the kinetic resolution of the two epoxide pairs diastereoisomeric therebetween (mixture 1), allowing to avoid complex chromatographic separations.

IPC Classes  ?

• C07D 311/00 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings

Abstract

The present invention relates to a novel process for the synthesis of the Nebivolol product depicted in Scheme 1, comprised of a reduced number of high-yield steps, and characterized by the enzymatic resolution of the chroman ester precursor.

IPC Classes  ?

• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4

Abstract

The present invention relates to a novel process for the synthesis of the Nebivolol product depicted in Scheme 1, comprised of a reduced number of high-yield steps, and characterized by the enzymatic resolution of the chroman ester precursor.

IPC Classes  ?

• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4

Abstract

The present invention relates to an association of active principles, i.e. of a xanthine oxidase inhibitor with one or more calcium antagonists, pharmaceutical compositions comprising said active principles, for use in a human or veterinary therapeutic treatment, and methods for the preparation thereof.

IPC Classes  ?

• A61K 31/426 - 1,3-Thiazoles
• A61K 31/4422 - 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61P 9/12 - Antihypertensives

Abstract

The present invention relates to the association of active principles, i.e. of a xanthine oxidase inhibitor with one or more HMG CoA reductase inhibitors, pharmaceutical compositions comprising said active principles, for use in a human or veterinary therapeutic treatment, and methods for the preparation thereof.

IPC Classes  ?

• A61K 31/426 - 1,3-Thiazoles
• A61P 9/12 - Antihypertensives
• A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• A61K 31/405 - Indole-alkanecarboxylic acidsDerivatives thereof, e.g. tryptophan, indomethacin
• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
• A61K 31/366 - Lactones having six-membered rings, e.g. delta-lactones
• A61K 31/47 - QuinolinesIsoquinolines
• A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim

Abstract

The present invention relates to an association of active principles, i.e. of a xanthine oxidase inhibitor with one or more angiotensin II receptor antagonists, pharmaceutical compositions comprising said active principles, for use in a therapeutic treatment in humans or animals, and methods for the preparation thereof.

IPC Classes  ?

• A61K 31/426 - 1,3-Thiazoles
• A61P 9/12 - Antihypertensives
• A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
• A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles

Abstract

The present invention relates to the association of active principles, i.e. of a xanthine oxidase inhibitor with a biguanide derivative, preferably metformin, pharmaceutical compositions comprising said active principles, for use in a human or veterinary therapeutic treatment, and methods for the preparation thereof.

IPC Classes  ?

• A61K 31/155 - Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (HN=C(OH)NH2), isothiourea (HN=C(SH)—NH2)
• A61K 31/426 - 1,3-Thiazoles
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Abstract

A two-dose autoinjector for a medicament wherein the locking and releasing of the drive spring (27) of the autoinjector is controlled through stepped guide means (16, 24) with ramps for two successive slidings therealong of slide means (28, 29) operated by the spring and connected with the syringe (21) and relevant plunger (26). The guide means and the slide means are pivotable relative to one another and the sliding direction, while the syringe can only slide axially, and the triggering control for each sliding is obtained by pressing a trigger (30), axially slidable relative to a stationary member (1), against the patient's skin to push the slide means first into one ramp and then into the other ramp of the guide means. To enable or disable the sliding of the slide means within the guide means a angularly mobile arming member (11) is provided formed with a guide track (14) substantially equal to that of the stationary member where the guide means are formed. Following two subsequent angular arming displacements of the mobile member relative to the stationary member the ramps and the guide track are radially aligned to enable the slide means to slide under the action of the spring and therefore deliver the first dose and then the second dose.

IPC Classes  ?

• A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
• A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
• A61M 5/50 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests having means for preventing re-use, or for indicating if defective, used, tampered with or unsterile

Abstract

A two-dose autoinjector for a medicament wherein the locking and releasing of the drive spring (27) of the autoinjector is controlled through stepped guide means (16, 24) with ramps for two successive slidings therealong of slide means (28, 29) operated by the spring and connected with the syringe (21) and relevant plunger (26). The guide means and the slide means are pivotable relative to one another and the sliding direction, while the syringe can only slide axially, and the triggering control for each sliding is obtained by pressing a trigger (30), axially slidable relative to a stationary member (1), against the patient's skin to push the slide means first into one ramp and then into the other ramp of the guide means. To enable or disable the sliding of the slide means within the guide means a angularly mobile arming member (11) is provided formed with a guide track (14) substantially equal to that of the stationary member where the guide means are formed. Following two subsequent angular arming displacements of the mobile member relative to the stationary member the ramps and the guide track are radially aligned to enable the slide means to slide under the action of the spring and therefore deliver the first dose and then the second dose.

IPC Classes  ?

• A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
• A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
• A61M 5/50 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests having means for preventing re-use, or for indicating if defective, used, tampered with or unsterile

Abstract

The present invention relates to a novel process for the synthesis of Nebivolol product represented in Scheme (1), comprised of a reduced number of high-yield steps, and characterized by the kinetic resolution of the two epoxide pairs diastereoisomeric therebetween (mixture 1), allowing to avoid complex chromatographic separations.

IPC Classes  ?

• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4

Abstract

The present invention relates to a novel process for the synthesis of Nebivolol product represented in Scheme (1), comprised of a reduced number of high-yield steps, and characterized by the kinetic resolution of the two epoxide pairs diastereoisomeric therebetween (mixture 1), allowing to avoid complex chromatographic separations.

IPC Classes  ?

• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4

Abstract

There are disclosed pharmaceutical compositions containing MUC 16 fragments with antigenic activity and their use for the preparation of antitumor vaccines.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The present invention refers to a pharmaceutical composition for parenteral administration as vaccine comprising a monoclonal antibody and as adjuvant an aluminium derivative.

IPC Classes  ?

• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum

Abstract

The use of a known compound of formula (I) is described for preparing pharmaceutical formulations useful in the treatment of melanoma.

IPC Classes  ?

• A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
• A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
• A61P 35/00 - Antineoplastic agents