JP2002512189A - Treatment of general anxiety with paroxetine - Google Patents

Abstract

  (57) [Summary] A method of treating general anxiety comprising administering to a human or non-human animal in need thereof an effective and non-toxic amount of paroxetine or a pharmaceutically acceptable salt or solvate thereof. .

Description

DETAILED DESCRIPTION OF THE INVENTION

TECHNICAL FIELD [0001] The present invention relates to methods of treating generalized anxiety disorder, and in particular, the use of paroxetine in such treatment.

BACKGROUND OF THE INVENTION Pharmaceuticals with antidepressant and antiparkinsonian activity are disclosed in US Pat.
No. 3 and U.S. Pat. No. 4,007,196. A particularly important compound is paroxetine, that is, 4- (4′-fluorophenyl).
) -3- (3 ', 4'-Methylenedioxyphenoxymethyl) -piperidine is the (-) trans isomer (see Example 2 of U.S. Patent No. 4,007,196). Paroxetine hydrochloride has been approved for use in humans in therapy to treat depression, obsessive-compulsive disorder (OCD) and panic disease, among others. For commercial use, paroxetine hydrochloride is supplied as a crystalline hemihydrate (see EP-A 0223403 of the Beecham Group). Various crystalline anhydrous forms are also known (WO 96 / SmithKline Beecham plc).
24595).

DISCLOSURE OF THE INVENTION It has now surprisingly been discovered that paroxetine has therapeutic potential as a medicament for treating general anxiety. Accordingly, the present invention is a method of treating general anxiety, comprising administering an effective and non-toxic amount of paroxetine or a pharmaceutically acceptable salt or solvate thereof to a human or non-human animal in need of such treatment. Providing a method, comprising: The present invention also provides the use of paroxetine or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for use in treating general anxiety. A preferred pharmaceutically acceptable salt of paroxetine is the crystalline hydrochloride salt. A suitable method for preparing paroxetine hydrochloride is described in US Pat.
Nos. 1723, 490801, 4861893 and 5039803
And the methods described in PCT / GB93 / 00721. E
Hemihydrate produced as in PA 0223403 is particularly preferred.

Pharmaceuticals used for the treatment of general anxiety can be prepared by mixing paroxetine or a pharmaceutically acceptable salt or solvate thereof with a suitable carrier,
As is conventional, they may contain diluents, binders, fillers, disintegrants, flavoring agents, coloring agents, lubricants or preservatives. Preferably, the medicament is in unit dosage form and is in a form suitable for use in medicine in the field of veterinary medicine. For example, such preparations may be in packaged form with written or printed instructions for use as a therapeutic for the treatment of general anxiety.

[0005] Suitable dosage forms of paroxetine or a pharmaceutically acceptable salt or solvate will depend on the severity of the general anxiety disorder and the condition of the patient. The dosage form is also, inter alia,
The relevance of the efficacy to absorbability and the frequency and route of administration will depend. Paroxetine or a pharmaceutically acceptable salt or solvate thereof can be formulated for administration by any route, for example, oral, sublingual, rectal, topical,
It can be formulated for parenteral, intravenous or intramuscular administration. If desired, paroxetine may be designed to provide delayed release of paroxetine or a pharmaceutically acceptable salt or solvate thereof. The medicament can be, for example, in the form of tablets, capsules, sachets, vials, powders, granules, lozenges, reconstitutable powders, or liquid preparations, such as solutions or suspensions, or suppositories.

[0006] Pharmaceuticals such as those suitable for oral administration include binders such as syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone; fillers such as lactose, sucrose, corn starch, calcium phosphate, sorbitol or glycerin. Tablet lubricants, such as magnesium stearate;
Disintegrants may include conventional excipients such as starch, polyvinylpyrrolidone, sodium starch glycolate or microcrystalline cellulose; or pharmaceutically acceptable gelling agents, such as sodium lauryl sulfate. A solid medicine can be obtained by a conventional operation such as blending, filling and tableting. Paroxetine or a salt or solvate thereof can be distributed throughout the drug utilizing a large amount of filler using an iterative mixing operation. When the medicament is in the form of a tablet, powder or lozenge, any carrier suitable for formulating solid pharmaceutical compositions can be used, for example, magnesium stearate, starch, glucose, lactose, sucrose, rice flour and chalk. . Tablets may be coated according to well known methods in normal pharmaceutical practice, especially with enteric coatings. The medicament can also be, for example, optionally with a carrier or other excipient,
It may be in the form of a capsule for oral ingestion of gelatin containing paroxetine or a salt thereof.

[0007] Pharmaceuticals for oral administration which are liquids may be in the form of, for example, emulsions, syrups or elixirs, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid medicaments include suspending agents such as sorbitol, syrup, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel,
Hardened edible fat; emulsifiers, for example, lecithin, sorbitan monooleic acid or acacia; aqueous or non-aqueous vehicles, which may contain edible oils, for example, tonsils oil, fractionated coconut oil, and oily esters, for example, glycerin or Esters of propylene glycol or ethyl alcohol, glycerin, water or saline; preservatives, such as methyl or propyl p-hydroxybenzoate or sorbic acid; and, if desired, conventional such as conventional flavoring or coloring agents. An additive may be contained.

[0008] Paroxetine or a pharmaceutically acceptable salt or solvate thereof can also be administered by the parenteral route. According to conventional pharmaceutical procedures, the medicament may be formulated for rectal administration, for example, as a suppository. They are also pharmaceutically acceptable liquids,
For example, they may be formulated for administration in injectable form, either as an aqueous or non-aqueous solution, or as a suspension or emulsion, in sterile pyrogen-free water or a parenterally acceptable oil or liquid mixture. . The liquid contains bacteriostats, antioxidants or other preservatives, buffers or solutes that make the solution isotonic with blood, thickeners, suspending agents or other pharmaceutically acceptable additives. You can also. Such forms are provided in unit dose form, such as in ampules or disposable syringes, or in multi-dose forms, such as solid forms or concentrates, which can be used to prepare bottles or injectable forms from which appropriate quantities can be taken. Will be done.

[0009] As noted above, the effective amount of paroxetine or pharmaceutically acceptable salt or solvate will depend on the severity of the general anxiety disorder to be treated, the condition of the patient, the frequency or route of administration. Unit doses generally contain from 2 to 1000 mg, from 30 to 500 mg, in particular from 20, 50, 100, 150, 200, 250, 300,
It preferably contains 350, 400, 450 or 500 mg. The composition is administered one or more times a day, for example, two, three or four times a day, with a total daily dose generally ranging from 100 to 3000 mg for a 70 kg adult. There will be. Preferably, the unit dose contains 2 to 20 mg paroxetine (calculated as the free base) and is administered multiple times, if desired, to administer the daily dose described above. The present invention further relates to a pharmaceutical composition for use in the treatment of general anxiety, comprising an effective amount of paroxetine or a pharmaceutically acceptable salt or solvate thereof.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier. Such a composition can be prepared according to the methods described above.

Examples The following examples are used to disclose suitable pharmaceutical compositions for use in the present invention. EXAMPLES The following ingredients are mixed in a conventional manner and compressed into tablets of about 300 mg weight containing about 20 mg of paroxetine (calculated as free base).

Paroxetine hydrochloride hemihydrate 228.8 g Dibasic calcium phosphate dihydrate 2441.2 g Hydroxypropyl methylcellulose 2910 150.0 g Sodium starch glycolate 150.0 g Magnesium stearate 30.0 g Total weight of tablets 3000. 0g

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Claims (4)

[Claims] 1. A method for treating general anxiety, comprising administering an effective and non-toxic amount of paroxetine or a pharmaceutically acceptable salt or solvate thereof to a human or non-human mammal in need of such treatment. A treatment that involves doing. 2. Use of paroxetine or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for use in treating general anxiety. 3. A pharmaceutical composition for treating general anxiety comprising an effective amount of paroxetine or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier. 4. The method according to claim 1, wherein the pharmaceutically acceptable salt of paroxetine is its hydrochloride, or the pharmaceutical composition according to claim 3 or claim 3.