WO1999002142A2 - Novel composition comprising an ssri and a beta-blocker - Google Patents

Novel composition comprising an ssri and a beta-blocker Download PDF

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Publication number
WO1999002142A2
WO1999002142A2 PCT/EP1998/004971 EP9804971W WO9902142A2 WO 1999002142 A2 WO1999002142 A2 WO 1999002142A2 EP 9804971 W EP9804971 W EP 9804971W WO 9902142 A2 WO9902142 A2 WO 9902142A2
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
blocker
composition according
ssri
pindolol
Prior art date
Application number
PCT/EP1998/004971
Other languages
French (fr)
Other versions
WO1999002142A3 (en
Inventor
Paul John Cummings
Ian Frederic Tulloch
Original Assignee
Smithkline Beecham P.L.C.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to KR1020007000202A priority Critical patent/KR20010021644A/en
Priority to SK7-2000A priority patent/SK72000A3/en
Priority to BR9810996-0A priority patent/BR9810996A/en
Priority to AU93401/98A priority patent/AU9340198A/en
Application filed by Smithkline Beecham P.L.C. filed Critical Smithkline Beecham P.L.C.
Priority to IL13386998A priority patent/IL133869A0/en
Priority to EP98946294A priority patent/EP0996466A2/en
Priority to JP50818599A priority patent/JP2002508003A/en
Priority to PL98338017A priority patent/PL338017A1/en
Priority to APAP/P/1999/001728A priority patent/AP2000001728A0/en
Priority to EA200000112A priority patent/EA200000112A1/en
Priority to CA002295822A priority patent/CA2295822A1/en
Publication of WO1999002142A2 publication Critical patent/WO1999002142A2/en
Publication of WO1999002142A3 publication Critical patent/WO1999002142A3/en
Priority to NO20000107A priority patent/NO20000107D0/en
Priority to BG104119A priority patent/BG104119A/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs

Definitions

  • This invention is concerned with novel formulations of selective serotonin re-uptake inhibitors (SSRI's).
  • SSRI's selective serotonin re-uptake inhibitors
  • the present invention provides formulations that potentiate the therapeutic activity of an SSRI, and especially that improve the onset of the therapeutic effect.
  • a problem with any co-administration regime is ensuring patient compliance, particularly in a regime such as proposed by Artigas which involves taking medication on three occasions during the day (assuming that the paroxetine dose and the first pindolol dose are taken simultaneously).
  • the present invention aims to overcome the problems associated with co-administration of SSRIs and potentiating compounds.
  • the present invention provides an SSRI composition
  • an SSRI composition comprising an SSRI in quick release form and a ⁇ -blocker in sustained release form.
  • the composition is conveniently in tablet or capsule form.
  • SSRIs used in this invention are paroxetine, fluvoxamine, citalopram and sertraline.
  • the SSRI is paroxetine.
  • the co-administered ⁇ -blocker is preferably pindolol.
  • the preferred combination of SSRI and ⁇ -blocker is paroxetine and pindolol.
  • the tablet or capsule contains 20 mg of paroxetine in an immediate release form and 7.5 mg of pindolol in a sustained release form.
  • the sustained release form of the ⁇ -blocker is provided to release the equivalent of a three times daily dose continuously over a period of 12-16 hours. Alternatively, the dose may be released in three spaced tranches.
  • the composition of the invention is preferably presented as a bi-layer tablet in which one layer contains an SSRI in a conventional quick release formulation and the other layer contains a ⁇ -blocker in a sustained release formulation.
  • the sustained release may be provided by formulating the ⁇ -blocker with any conventional sustained release excipient or blend of excipients that does not interact with the ⁇ -blocker or the SSRI.
  • the sustained release properties are provided by incorporating the ⁇ -blocker in an excipient which swells in gastric juice, typically forming a gel which dissolves and/or is abraded as the tablet passes through the patient's gut, releasing the active ingredient.
  • the rate of release may be controlled in a conventional manner by varying the molecular weight of the excipient and/or co-formulating a primary excipient with materials that dissolve or disintegrate at a different rate than the primary excipient, to form micropores in a swollen or gelled primary excipient.
  • Suitable primary excipients may be selected from swellable binders such as methyl cellulose for example as sold under the trade mark Methocel K4M and E5, ethyl cellulose, polyacrylic acid for example as sold under the trade mark Carbopol 974P, polyacrylic esters for example as sold under the trade mark Eudragit L30D and RS30D, xanthan gum, and starch.
  • swellable binders such as methyl cellulose for example as sold under the trade mark Methocel K4M and E5, ethyl cellulose, polyacrylic acid for example as sold under the trade mark Carbopol 974P, polyacrylic esters for example as sold under the trade mark Eudragit L30D and RS30D, xanthan gum, and starch.
  • the release profile of the primary excipient may be varied by incorporating fillers and disintegrants such as lactose especially lactose monohydrate, microcrystalline cellulose for example as sold under the trade mark Avicel pH102, calcium sulphate, dicalcium phosphate for example as sold under the trade mark Encompress, polyvinyl pyrrolidone for example as sold under the trade mark Povidone 30, hydrogenated vegetable oils for example as sold under the trade mark Lubritab.
  • lactose especially lactose monohydrate
  • microcrystalline cellulose for example as sold under the trade mark Avicel pH102
  • calcium sulphate for example as sold under the trade mark Encompress
  • polyvinyl pyrrolidone for example as sold under the trade mark Povidone
  • hydrogenated vegetable oils for example as sold under the trade mark Lubritab.
  • compositions may be a capsule presentation comprising coated pellets of a ⁇ -blocker, which is a mixture of coated pellets having different dissolution times, dispersed in a powder formulation of an SSRI, all contained within a soluble capsule.
  • the coating of the pellets of the ⁇ -blocker is a material that is resistant to gastric juices but dissolves in the gut, for example. Dissolution times may be varied by varying the coating thickness.
  • the coated pellets are mixed so as to provide a substantially continuous release of pindolol, but if desired the pellets may be a mixture of three coating thicknesses so that pindolol is released in three tranches over a the desired dosage period such as 12-14 hours.
  • a powdered formulation of the SSRI be be made by blending the SSRI with conventional excipients. Soluble capsules to contain the combination of active ingredients may be conventionally made from gelatine.
  • sustained release formulations of the above described hydrophilic matrix type and enteric coating type that may be used in this invention are disclosed in standard textbooks on the subject.
  • sustained release ⁇ -blocker formulation has a release profile measured in vitro in acid/buffer which has a dissolution time T 50 o /o of 1.73 hours, a T 90 o /o of 8.45 hours and a T 100 o /o of 14 hours.
  • a preferred embodiment of the invention provides a formulation of an SSRI and a ⁇ -blocker in which the ⁇ -blocker is in a sustained release form having a release profile in vitro in which the T 50 o /o is 1.73 hours ⁇ 20%, the T 90 o /o is 8.45 hours ⁇ 20% and the T 100 o /o is 14 hours ⁇ 20%.
  • the SSRI is paroxetine hydrochloride, most preferably at a dosage of 20 mg
  • the ⁇ -blocker is pindolol, most preferably at a dosage of 7.5 mg.
  • pindolol is typically used as the commercially available racemate. However, active isomers thereof may be used at a dosage adjusted for bioquivalence to a stated dose of the racemate.
  • compositions of this invention include treatment of alcoholism, anxiety, depression, obsessive compulsive disorder (OCD), panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, premenstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia and substance abuse; referred to herein as "the Disorders”.
  • the present invention also provides
  • a method for the treatment or prophylaxis of the Disorders which comprises administering a tablet or capsule comprising an SSRI and a sustained release form of a ⁇ - blocker to a person or animal in need thereof.
  • the tablet or capsule is preferably a composition of this invention having the preferred values indicated above.
  • Bi-layer tablets of paroxetine and sustained release pindolol were manufactured as follows.
  • a sustained release form of pindolol based upon a hydrophilic matrix with a soluble filler/disintegrant to increase the porosity of the matrix once hydrated was prepared by high shear wet granulation of a mixture of :
  • pindolol base 7.5 parts by weight methylcellulose (Methocel K4M) 35 parts by weight lactose monohydrate 25 parts by weight microcrystalline cellulose (Avicel pH 102) 32 parts by weight
  • paroxetine hydrochloride An immediate release formulation of paroxetine was prepared by blending 20 parts per weight of paroxetine hydrochloride and 80 parts per weight of conventional excipients.
  • 100 mg. amounts of the sustained release pindolol formulation were charged into tablet moulds in a rotary tableting platen at a first charging station. After a preliminary light pressing to locate the powdered formulation in the tablet mould, the platen was indexed to a second charging station where 152 mg. of the paroxetine formulation were introduced on top of the sustained release formulation. The two layer mixture in the tablet mould was then given a full press to prepare 252 mg. tablets containing 20 mg. paroxetine hydrochloride and 7.5 mg. pindolol in a sustained release base, each active component being in separate layers of a bi-layer tablet.

Abstract

A pharmaceutical composition comprising an SSRI in quick-release form and a β-blocker in sustained-release form.

Description

NOVEL COMPOSITION
This invention is concerned with novel formulations of selective serotonin re-uptake inhibitors (SSRI's). In particular the present invention provides formulations that potentiate the therapeutic activity of an SSRI, and especially that improve the onset of the therapeutic effect.
Artigas et al (Arch. Gen Psychiatry, Vol. 51, pp 248-251, Mar. 1994) have reported that administration of pindolol (2.5 mg. three times a day) during treatment with the SSRI paroxetine (20 mg once per day) relieved depression in patients previously showing no benefit from treatment with paroxetine.
Subsequently, it has been proposed in EP-A-0714663 that the effect of the SSRIs citaloprolam, fluvoxamine and paroxetine can be potentiated by co-administration in certain combinations with inter alia pindolol, penbutolol, propranol and tertatolol and other compounds known to be serotonin IA receptor antagonists, but excluding the combination paroxetine-pindolol.
A problem with any co-administration regime is ensuring patient compliance, particularly in a regime such as proposed by Artigas which involves taking medication on three occasions during the day (assuming that the paroxetine dose and the first pindolol dose are taken simultaneously).
The present invention aims to overcome the problems associated with co-administration of SSRIs and potentiating compounds.
In its broadest aspect, the present invention provides an SSRI composition comprising an SSRI in quick release form and a β-blocker in sustained release form. The composition is conveniently in tablet or capsule form.
Typical SSRIs used in this invention are paroxetine, fluvoxamine, citalopram and sertraline. Preferably the SSRI is paroxetine. The co-administered β-blocker is preferably pindolol.
The preferred combination of SSRI and β-blocker is paroxetine and pindolol. Preferably the tablet or capsule contains 20 mg of paroxetine in an immediate release form and 7.5 mg of pindolol in a sustained release form. Typically the sustained release form of the β-blocker is provided to release the equivalent of a three times daily dose continuously over a period of 12-16 hours. Alternatively, the dose may be released in three spaced tranches.
When the SSRI is combined with a β-blocker in a continuous release formulation, then the composition of the invention is preferably presented as a bi-layer tablet in which one layer contains an SSRI in a conventional quick release formulation and the other layer contains a β-blocker in a sustained release formulation.
The sustained release may be provided by formulating the β-blocker with any conventional sustained release excipient or blend of excipients that does not interact with the β-blocker or the SSRI.
Suitably, the sustained release properties are provided by incorporating the β-blocker in an excipient which swells in gastric juice, typically forming a gel which dissolves and/or is abraded as the tablet passes through the patient's gut, releasing the active ingredient. The rate of release may be controlled in a conventional manner by varying the molecular weight of the excipient and/or co-formulating a primary excipient with materials that dissolve or disintegrate at a different rate than the primary excipient, to form micropores in a swollen or gelled primary excipient.
Suitable primary excipients may be selected from swellable binders such as methyl cellulose for example as sold under the trade mark Methocel K4M and E5, ethyl cellulose, polyacrylic acid for example as sold under the trade mark Carbopol 974P, polyacrylic esters for example as sold under the trade mark Eudragit L30D and RS30D, xanthan gum, and starch.
The release profile of the primary excipient may be varied by incorporating fillers and disintegrants such as lactose especially lactose monohydrate, microcrystalline cellulose for example as sold under the trade mark Avicel pH102, calcium sulphate, dicalcium phosphate for example as sold under the trade mark Encompress, polyvinyl pyrrolidone for example as sold under the trade mark Povidone 30, hydrogenated vegetable oils for example as sold under the trade mark Lubritab.
Conventional tableting excipients may also be included to assist tablet manufacture, for example as die lubricants etc., such as magnesium stearate, glyceryl behenate for example as sold under the trade mark Compritol 888. Alternatively, the composition may be a capsule presentation comprising coated pellets of a β-blocker, which is a mixture of coated pellets having different dissolution times, dispersed in a powder formulation of an SSRI, all contained within a soluble capsule.
Suitably, the coating of the pellets of the β-blocker is a material that is resistant to gastric juices but dissolves in the gut, for example. Dissolution times may be varied by varying the coating thickness. Preferably the coated pellets are mixed so as to provide a substantially continuous release of pindolol, but if desired the pellets may be a mixture of three coating thicknesses so that pindolol is released in three tranches over a the desired dosage period such as 12-14 hours. A powdered formulation of the SSRI be be made by blending the SSRI with conventional excipients. Soluble capsules to contain the combination of active ingredients may be conventionally made from gelatine.
Typical sustained release formulations of the above described hydrophilic matrix type and enteric coating type that may be used in this invention are disclosed in standard textbooks on the subject.
We have found that a suitable release profile for clinical use is obtained when the sustained release β-blocker formulation has a release profile measured in vitro in acid/buffer which has a dissolution time T50o/o of 1.73 hours, a T90o/o of 8.45 hours and a T100o/o of 14 hours.
Accordingly, a preferred embodiment of the invention provides a formulation of an SSRI and a β-blocker in which the β-blocker is in a sustained release form having a release profile in vitro in which the T50o/o is 1.73 hours ± 20%, the T90o/o is 8.45 hours ± 20% and the T100o/o is 14 hours ± 20%.
Preferably, the SSRI is paroxetine hydrochloride, most preferably at a dosage of 20 mg, and the β-blocker is pindolol, most preferably at a dosage of 7.5 mg.
The pindolol is typically used as the commercially available racemate. However, active isomers thereof may be used at a dosage adjusted for bioquivalence to a stated dose of the racemate.
Therapeutic uses of compositions of this invention, especially compositions of paroxetine hydrochloride and pindolol, include treatment of alcoholism, anxiety, depression, obsessive compulsive disorder (OCD), panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, premenstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia and substance abuse; referred to herein as "the Disorders".
Accordingly, the present invention also provides
use of an SSRI and a sustained release form of a β-blocker for the manufacture of a tablet or capsule for the treatment or prophylaxis of the Disorders in humans and animals, and
a method for the treatment or prophylaxis of the Disorders, which comprises administering a tablet or capsule comprising an SSRI and a sustained release form of a β- blocker to a person or animal in need thereof.
In the use and method of the invention, the tablet or capsule is preferably a composition of this invention having the preferred values indicated above.
The invention is illustrated by the following Example:
Example 1
Bi-layer tablets of paroxetine and sustained release pindolol were manufactured as follows.
Pindolol Component
A sustained release form of pindolol based upon a hydrophilic matrix with a soluble filler/disintegrant to increase the porosity of the matrix once hydrated was prepared by high shear wet granulation of a mixture of :
pindolol base 7.5 parts by weight methylcellulose (Methocel K4M) 35 parts by weight lactose monohydrate 25 parts by weight microcrystalline cellulose (Avicel pH 102) 32 parts by weight
After drying and screening, 0.5 parts by weight of glyceryl behenate (Compritol 888) as a lubricant were incorporated by tumble blending. Paroxetine Component
An immediate release formulation of paroxetine was prepared by blending 20 parts per weight of paroxetine hydrochloride and 80 parts per weight of conventional excipients.
Tableting
100 mg. amounts of the sustained release pindolol formulation were charged into tablet moulds in a rotary tableting platen at a first charging station. After a preliminary light pressing to locate the powdered formulation in the tablet mould, the platen was indexed to a second charging station where 152 mg. of the paroxetine formulation were introduced on top of the sustained release formulation. The two layer mixture in the tablet mould was then given a full press to prepare 252 mg. tablets containing 20 mg. paroxetine hydrochloride and 7.5 mg. pindolol in a sustained release base, each active component being in separate layers of a bi-layer tablet.

Claims

Claims
1. A pharmaceutical composition comprising an SSRI in quick-release form and a ╬▓- blocker in sustained-release form.
2. A pharmaceutical composition according to claim 1 which takes the form of a bi-layer tablet in which one layer contains the SSRI in a quick-release formulation and the other layer contains the ╬▓-blocker in a sustained-release formulation.
3. A pharmaceutical composition according to claim 1 which takes the form of a capsule which contains an admixture of a quick-release formulation of the SSRI and a sustained- release formulation of the ╬▓-blocker.
4. A pharmaceutical composition according to any one of claims 1 to 3 in which the ╬▓- blocker is in a sustained release form having a release profile in vitro in which the T50o/o is 1.73 hours ┬▒ 20%, the T90o/o is 8.45 hours ┬▒ 20% and the T100o/o is 14 hours ┬▒ 20%.
5. A pharmaceutical composition according to any one of claims 1 to 4 in which the SSRI is paroxetine or a pharmaceutically acceptable derivative thereof.
6. A pharmaceutical composition according to claim 5 in which the paroxetine is in the form of the hydrochloride.
7. A pharmaceutical composition according to any one of claims 1 to 6 in which the ╬▓- blocker is pindolol.
8. A pharmaceutical composition according to claim 7 in which the pindolol is present as the racemate.
9. A pharmaceutical composition according to claim 8 which contains 20mg of paroxetine hydrochloride and 7.5mg of pindolol as the racemate.
10. A pharmaceutical composition according to claim 7 in which the pindolol is present as an active isomer.
11. A method of treatment of alcoholism, anxiety, depression, obsessive compulsive disorder (OCD), panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, premenstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia, and substance abuse which comprises administering an effective or prophylactic amount of a pharmaceutical composition as defined in claim 1 according to any one of claims 1 to 10 to a sufferer in need thereof.
12. The use of a pharmaceutical composition as defined in claims 1 to 10 in the manufacture of a medicament for the treatment or prevention of alcoholism, anxiety, depression, obsessive compulsive disorder (OCD), panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, premenstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia, and substance abuse.
13. A pharmaceutical composition as defined in claims 1 to 10 for use in the treatment or prevention of alcoholism, anxiety, depression, obsessive compulsive disorder (OCD), panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, premenstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia, and substance abuse.
PCT/EP1998/004971 1997-07-11 1998-07-07 Novel composition comprising an ssri and a beta-blocker WO1999002142A2 (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
EP98946294A EP0996466A2 (en) 1997-07-11 1998-07-07 Novel composition comprising an ssri and a beta-blocker
BR9810996-0A BR9810996A (en) 1997-07-11 1998-07-07 Pharmaceutical composition
AU93401/98A AU9340198A (en) 1997-07-11 1998-07-07 Novel composition
PL98338017A PL338017A1 (en) 1997-07-11 1998-07-07 Novel composition
IL13386998A IL133869A0 (en) 1997-07-11 1998-07-07 Novel composition novel formulations comprising an ssri in combination with a beta blocker
SK7-2000A SK72000A3 (en) 1997-07-11 1998-07-07 Novel composition comprising an ssri and a beta-blocker
JP50818599A JP2002508003A (en) 1997-07-11 1998-07-07 Novel composition
KR1020007000202A KR20010021644A (en) 1997-07-11 1998-07-07 Novel Comosition
APAP/P/1999/001728A AP2000001728A0 (en) 1997-07-11 1998-07-07 Novel composition.
EA200000112A EA200000112A1 (en) 1997-07-11 1998-07-07 NEW COMPOSITION
CA002295822A CA2295822A1 (en) 1997-07-11 1998-07-07 Novel composition
NO20000107A NO20000107D0 (en) 1997-07-11 2000-01-10 New mixture
BG104119A BG104119A (en) 1997-07-11 2000-02-01 A new composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9714675.7 1997-07-11
GBGB9714675.7A GB9714675D0 (en) 1997-07-11 1997-07-11 Novel composition

Publications (2)

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WO1999002142A2 true WO1999002142A2 (en) 1999-01-21
WO1999002142A3 WO1999002142A3 (en) 1999-04-15

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PCT/EP1998/004971 WO1999002142A2 (en) 1997-07-11 1998-07-07 Novel composition comprising an ssri and a beta-blocker

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EP (1) EP0996466A2 (en)
JP (1) JP2002508003A (en)
KR (1) KR20010021644A (en)
CN (1) CN1262627A (en)
AP (1) AP2000001728A0 (en)
AR (1) AR016128A1 (en)
AU (1) AU9340198A (en)
BG (1) BG104119A (en)
BR (1) BR9810996A (en)
CA (1) CA2295822A1 (en)
CO (1) CO4950552A1 (en)
DZ (1) DZ2556A1 (en)
EA (1) EA200000112A1 (en)
GB (1) GB9714675D0 (en)
HU (1) HUP0003074A3 (en)
ID (1) ID24191A (en)
IL (1) IL133869A0 (en)
MA (1) MA24604A1 (en)
NO (1) NO20000107D0 (en)
OA (1) OA11276A (en)
PE (1) PE99699A1 (en)
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WO2006030306A2 (en) * 2004-09-17 2006-03-23 Neurocure Ltd Pindolol for treating premenstrual syndrome and premenstrual dysphoric disorder
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US8119163B2 (en) 1998-11-02 2012-02-21 Alkermes Pharma Ireland Limited Nanoparticulate and controlled release compositions comprising cefditoren
US9056052B1 (en) 2000-10-30 2015-06-16 Purdue Pharma L.P. Controlled release hydrocodone formulations
US9669022B2 (en) 1999-10-29 2017-06-06 Purdue Pharma L.P. Controlled release hydrocodone formulations
US10179130B2 (en) 1999-10-29 2019-01-15 Purdue Pharma L.P. Controlled release hydrocodone formulations

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Cited By (17)

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US7417038B1 (en) 1998-10-15 2008-08-26 Imperial Innovations Limited Methods of treating cachexia
US7829596B2 (en) 1998-10-15 2010-11-09 Imperial Innovations Limited Methods of treatment
US8119163B2 (en) 1998-11-02 2012-02-21 Alkermes Pharma Ireland Limited Nanoparticulate and controlled release compositions comprising cefditoren
US9675611B1 (en) 1999-10-29 2017-06-13 Purdue Pharma L.P. Methods of providing analgesia
US9669024B2 (en) 1999-10-29 2017-06-06 Purdue Pharma L.P. Controlled release hydrocodone formulations
US10179130B2 (en) 1999-10-29 2019-01-15 Purdue Pharma L.P. Controlled release hydrocodone formulations
US10076516B2 (en) 1999-10-29 2018-09-18 Purdue Pharma L.P. Methods of manufacturing oral dosage forms
US9669022B2 (en) 1999-10-29 2017-06-06 Purdue Pharma L.P. Controlled release hydrocodone formulations
WO2001062341A3 (en) * 2000-02-22 2002-01-31 Knoll Gmbh Combination product for the treatment of obesity
WO2001062341A2 (en) * 2000-02-22 2001-08-30 Knoll Gmbh Combination product for the treatment of obesity
US9669023B2 (en) 2000-10-30 2017-06-06 Purdue Pharma L.P. Controlled release hydrocodone formulations
US9060940B2 (en) 2000-10-30 2015-06-23 Purdue Pharma L.P. Controlled release hydrocodone
US9682077B2 (en) 2000-10-30 2017-06-20 Purdue Pharma L.P. Methods of providing analgesia
US10022368B2 (en) 2000-10-30 2018-07-17 Purdue Pharma L.P. Methods of manufacturing oral formulations
US9056052B1 (en) 2000-10-30 2015-06-16 Purdue Pharma L.P. Controlled release hydrocodone formulations
WO2006030306A3 (en) * 2004-09-17 2006-09-08 Neurocure Ltd Pindolol for treating premenstrual syndrome and premenstrual dysphoric disorder
WO2006030306A2 (en) * 2004-09-17 2006-03-23 Neurocure Ltd Pindolol for treating premenstrual syndrome and premenstrual dysphoric disorder

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BR9810996A (en) 2000-08-08
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NO20000107D0 (en) 2000-01-10
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