CA2295822A1 - Novel composition - Google Patents
Novel composition Download PDFInfo
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- CA2295822A1 CA2295822A1 CA002295822A CA2295822A CA2295822A1 CA 2295822 A1 CA2295822 A1 CA 2295822A1 CA 002295822 A CA002295822 A CA 002295822A CA 2295822 A CA2295822 A CA 2295822A CA 2295822 A1 CA2295822 A1 CA 2295822A1
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- Prior art keywords
- pharmaceutical composition
- composition according
- blocker
- ssri
- pindolol
- Prior art date
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- 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
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
A pharmaceutical composition comprising an SSRI in quick-release form and a .beta.-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 ~5 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 2o 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 25 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 ~i-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 (3-blocker is preferably pindolol.
The preferred combination of SSRI and ~i-blocker is paroxetine and pindolol.
Preferably the tablet or capsule contains 20 mg of paroxetine in an immediate release form and 7.~
mg of pindolol in a sustained release form.
Typically the sustained release form of the (3-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 (3-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 (3-blocker in a sustained release formulation.
1o The sustained release may be provided by formulating the (3-Mocker with any conventional sustained release excipient or blend of excipients that does not interact with the (3-Mocker or the SSRI.
Suitably, the sustained release properties are provided by incorporating the (3-blocker in ~ 5 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 2o 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, 25 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 3o 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.
35 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 (3-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 (3-Mocker 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 to 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.
VVe have found that a suitable release profile for clinical use is obtained when the sustained release (3-blocker formulation has a release profile measured in vitro in 2o acid/buffer which has a dissolution time Tsooo of 1.73 hours, a T9oo~o of 8.45 hours and a T~oooo of 14 hours.
Accordingly, a preferred embodiment of the invention provides a formulation of an SSRI
and a (3-blocker in which the (3-blocker is in a sustained release form having a release profile in vitro in which the Tsoo~o is 1.73 hours + 20%, the T9ooa is 8.45 hours + 20% and the T, oooo is 14 hours + 20%.
Preferably, the SSRI is paroxetine hydrochloride, most preferably at a dosage of 20 mg, and the ~3-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 (3-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 to administering a tablet or capsule comprising an SSRI and a sustained release form of a ~i-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.
is The invention is illustrated by the following Example:
Example 1 2o 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 25 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 30 lactose monohydrate 25 parts by weight microcrystalline cellulose (Avicel pH102) 32 parts by weight After drying and screening, O.s parts by weight of glyceryl behenate (Compritol 888) as a lubricant were incorporated by tumble blending.
3s 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 1 o 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.S mg. pindolol in a sustained release base, each active component being in separate layers of a bi-layer tablet.
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 ~5 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 2o 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 25 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 ~i-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 (3-blocker is preferably pindolol.
The preferred combination of SSRI and ~i-blocker is paroxetine and pindolol.
Preferably the tablet or capsule contains 20 mg of paroxetine in an immediate release form and 7.~
mg of pindolol in a sustained release form.
Typically the sustained release form of the (3-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 (3-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 (3-blocker in a sustained release formulation.
1o The sustained release may be provided by formulating the (3-Mocker with any conventional sustained release excipient or blend of excipients that does not interact with the (3-Mocker or the SSRI.
Suitably, the sustained release properties are provided by incorporating the (3-blocker in ~ 5 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 2o 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, 25 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 3o 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.
35 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 (3-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 (3-Mocker 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 to 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.
VVe have found that a suitable release profile for clinical use is obtained when the sustained release (3-blocker formulation has a release profile measured in vitro in 2o acid/buffer which has a dissolution time Tsooo of 1.73 hours, a T9oo~o of 8.45 hours and a T~oooo of 14 hours.
Accordingly, a preferred embodiment of the invention provides a formulation of an SSRI
and a (3-blocker in which the (3-blocker is in a sustained release form having a release profile in vitro in which the Tsoo~o is 1.73 hours + 20%, the T9ooa is 8.45 hours + 20% and the T, oooo is 14 hours + 20%.
Preferably, the SSRI is paroxetine hydrochloride, most preferably at a dosage of 20 mg, and the ~3-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 (3-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 to administering a tablet or capsule comprising an SSRI and a sustained release form of a ~i-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.
is The invention is illustrated by the following Example:
Example 1 2o 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 25 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 30 lactose monohydrate 25 parts by weight microcrystalline cellulose (Avicel pH102) 32 parts by weight After drying and screening, O.s parts by weight of glyceryl behenate (Compritol 888) as a lubricant were incorporated by tumble blending.
3s 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 1 o 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.S mg. pindolol in a sustained release base, each active component being in separate layers of a bi-layer tablet.
Claims (13)
1. A pharmaceutical composition comprising an SSRI in quick-release form and a .beta.-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 .beta.-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 .beta.-blocker.
4. A pharmaceutical composition according to any one of claims 1 to 3 in which the .beta.-blocker is in a sustained release form having a release profile in vitro in which the T50% is 1.73 hours ~ 20%, the T90% is 8.45 hours ~ 20% and the T100% is 14 hours ~
20%.
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 .beta.-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.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9714675.7 | 1997-07-11 | ||
| GBGB9714675.7A GB9714675D0 (en) | 1997-07-11 | 1997-07-11 | Novel composition |
| PCT/EP1998/004971 WO1999002142A2 (en) | 1997-07-11 | 1998-07-07 | Novel composition comprising an ssri and a beta-blocker |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2295822A1 true CA2295822A1 (en) | 1999-01-21 |
Family
ID=10815744
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002295822A Abandoned CA2295822A1 (en) | 1997-07-11 | 1998-07-07 | Novel composition |
Country Status (26)
| Country | Link |
|---|---|
| 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) |
| PL (1) | PL338017A1 (en) |
| SK (1) | SK72000A3 (en) |
| TR (1) | TR200000074T2 (en) |
| WO (1) | WO1999002142A2 (en) |
| ZA (1) | ZA986138B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1121111E (en) | 1998-10-15 | 2010-05-17 | Imp Innovations Ltd | Compounds for the treatment of weight loss |
| JP4613275B2 (en) | 1998-11-02 | 2011-01-12 | エラン ファーマ インターナショナル，リミティド | Multiparticulate modified release composition |
| KR20130010512A (en) | 1999-10-29 | 2013-01-28 | 유로-셀티크 소시에떼 아노뉨 | Controlled release hydrocodone formulations |
| US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
| GB0004003D0 (en) * | 2000-02-22 | 2000-04-12 | Knoll Ag | Therapeutic agents |
| KR100960200B1 (en) | 2000-10-30 | 2010-05-27 | 유로-셀티크 소시에떼 아노뉨 | Controlled release hydrocodone formulations |
| WO2006030306A2 (en) * | 2004-09-17 | 2006-03-23 | Neurocure Ltd | Pindolol for treating premenstrual syndrome and premenstrual dysphoric disorder |
| CN100469356C (en) * | 2006-09-08 | 2009-03-18 | 山东益康药业有限公司 | Slowly released tablet of compound atenolol, and preparation method |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2732335C2 (en) * | 1976-07-27 | 1983-01-20 | Sandoz-Patent-GmbH, 7850 Lörrach | Tablet for the enteral administration of indolyloxyalkanolamine derivatives |
| CA2134038C (en) * | 1994-06-16 | 1997-06-03 | David Taiwai Wong | Potentiation of drug response |
| EP0714663A3 (en) * | 1994-11-28 | 1997-01-15 | Lilly Co Eli | Potentiation of drug response by a serotonin 1A receptor antagonist |
| DE69607904T2 (en) * | 1995-08-16 | 2000-10-05 | Eli Lilly And Co., Indianapolis | Potentiation of serotonin drug response |
| EP0792649A1 (en) * | 1996-02-29 | 1997-09-03 | Eli Lilly And Company | Treatment of sleep disorders |
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1997
- 1997-07-11 GB GBGB9714675.7A patent/GB9714675D0/en active Pending
-
1998
- 1998-07-07 BR BR9810996-0A patent/BR9810996A/en not_active Application Discontinuation
- 1998-07-07 CN CN98806975A patent/CN1262627A/en active Pending
- 1998-07-07 WO PCT/EP1998/004971 patent/WO1999002142A2/en not_active Application Discontinuation
- 1998-07-07 ID IDW20000035A patent/ID24191A/en unknown
- 1998-07-07 CA CA002295822A patent/CA2295822A1/en not_active Abandoned
- 1998-07-07 HU HU0003074A patent/HUP0003074A3/en unknown
- 1998-07-07 EP EP98946294A patent/EP0996466A2/en not_active Withdrawn
- 1998-07-07 KR KR1020007000202A patent/KR20010021644A/en not_active Application Discontinuation
- 1998-07-07 AP APAP/P/1999/001728A patent/AP2000001728A0/en unknown
- 1998-07-07 JP JP50818599A patent/JP2002508003A/en active Pending
- 1998-07-07 TR TR2000/00074T patent/TR200000074T2/en unknown
- 1998-07-07 EA EA200000112A patent/EA200000112A1/en unknown
- 1998-07-07 SK SK7-2000A patent/SK72000A3/en unknown
- 1998-07-07 IL IL13386998A patent/IL133869A0/en unknown
- 1998-07-07 AU AU93401/98A patent/AU9340198A/en not_active Abandoned
- 1998-07-07 PL PL98338017A patent/PL338017A1/en unknown
- 1998-07-08 DZ DZ980166A patent/DZ2556A1/en active
- 1998-07-10 CO CO98039260A patent/CO4950552A1/en unknown
- 1998-07-10 AR ARP980103371A patent/AR016128A1/en unknown
- 1998-07-10 PE PE1998000612A patent/PE99699A1/en not_active Application Discontinuation
- 1998-07-10 ZA ZA9806138A patent/ZA986138B/en unknown
- 1998-07-10 MA MA25165A patent/MA24604A1/en unknown
-
2000
- 2000-01-10 NO NO20000107A patent/NO20000107D0/en not_active Application Discontinuation
- 2000-01-11 OA OA1200000006A patent/OA11276A/en unknown
- 2000-02-01 BG BG104119A patent/BG104119A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MA24604A1 (en) | 1999-04-01 |
| AR016128A1 (en) | 2001-06-20 |
| PL338017A1 (en) | 2000-09-25 |
| CN1262627A (en) | 2000-08-09 |
| NO20000107L (en) | 2000-01-10 |
| TR200000074T2 (en) | 2000-05-22 |
| JP2002508003A (en) | 2002-03-12 |
| BG104119A (en) | 2000-12-29 |
| PE99699A1 (en) | 1999-12-21 |
| IL133869A0 (en) | 2001-04-30 |
| CO4950552A1 (en) | 2000-09-01 |
| OA11276A (en) | 2003-07-31 |
| BR9810996A (en) | 2000-08-08 |
| EP0996466A2 (en) | 2000-05-03 |
| NO20000107D0 (en) | 2000-01-10 |
| AU9340198A (en) | 1999-02-08 |
| AP2000001728A0 (en) | 2000-03-31 |
| WO1999002142A3 (en) | 1999-04-15 |
| DZ2556A1 (en) | 2003-02-15 |
| WO1999002142A2 (en) | 1999-01-21 |
| KR20010021644A (en) | 2001-03-15 |
| ZA986138B (en) | 2000-01-10 |
| GB9714675D0 (en) | 1997-09-17 |
| EA200000112A1 (en) | 2000-10-30 |
| HUP0003074A3 (en) | 2001-12-28 |
| SK72000A3 (en) | 2000-12-11 |
| ID24191A (en) | 2000-07-13 |
| HUP0003074A2 (en) | 2001-01-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |