CN1305379A - Method of treatment - Google Patents

Method of treatment Download PDF

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Publication number
CN1305379A
CN1305379A CN99807465A CN99807465A CN1305379A CN 1305379 A CN1305379 A CN 1305379A CN 99807465 A CN99807465 A CN 99807465A CN 99807465 A CN99807465 A CN 99807465A CN 1305379 A CN1305379 A CN 1305379A
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China
Prior art keywords
paroxetine
smoking
purposes
polymer
pharmaceutical salts
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CN99807465A
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Chinese (zh)
Inventor
M·X·斯泰纳
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SmithKline Beecham Corp
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SmithKline Beecham Corp
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Publication of CN1305379A publication Critical patent/CN1305379A/en
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    • 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
    • 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
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • 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
    • A61K31/465—Nicotine; Derivatives thereof
    • 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
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/5073—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 having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—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 having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • 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
    • A61P25/34—Tobacco-abuse
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Addiction (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Psychiatry (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

A method for promoting smoking cessation or reduction or preventing relapse smoking, comprises administering an effective, non-toxic amount of paroxetine or a pharmaceutically acceptable salt or solvate thereof, to human in need thereof.

Description

Therapeutic Method
The present invention relates to promote to give up smoking or reduce smoking capacity or prevent the method for smoking once again, and be particularly related to the purposes of paroxetine in this therapy.
The medicine of antidepressant and Kang Pajinsenshi is described among U.S. Pat-A-3912743 and the US-A-4007196.Wherein a kind of chemical compound of the particular importance of Miao Shuing is a paroxetine, 4-(4 '-fluorophenyl)-3-(3 ', 4 '-methylene-dioxy phenoxyl methyl) (-) transisomer (seeing the embodiment 2 of US-A-4007196) of piperidines.This chemical compound is a selectivity 5-hydroxy tryptamine reuptake inhibithors (SSRI).The hydrochlorate of paroxetine is permitted in people's the treatment, particularly treatment depression, obsessive-compulsive disorder (OCD) and fear.
In commercial use, paroxetine hydrochloride provides (EP-A-0223403 that sees Beecham Group) with the form of crystalline hemihydrate.Also known multiple crystalline, anhydrous form (seeing the WO96/24595 of SmithKline Beecham plc).
SSRI chemical compound such as fluoxetine and Sertraline be recommended to be used for the treatment of chemicals and to rely on (seeing US5130338) and comprise nicotine withdrawal symptoms (seeing US4940585 and US4999382).But though various clinical studies show that the fluoxetine pair factor relevant with smoking cessation is favourable as weight increase with drinking, it can not improve quit smoking rate and (see Mizes etc., Psychopharmacol.Bull.32, No.3,491; Sullivan etc., J.Clin.Pharmacol.29, No.9,850,1980).
Now being surprised to find paroxetine gives up smoking or reduces smoking capacity or prevent that smoking once again has potential therapeutic use for promoting as medicine.
Therefore, the invention provides and promote smoking cessation or reduce smoking capacity or prevent the method for smoking once again, that this method comprises is effective to the people who needs thus, paroxetine or its pharmaceutical salts or the hydrate of nontoxic amount.
The present invention also provides paroxetine or its pharmaceutical salts or hydrate to be used to promote to give up smoking or to reduce smoking capacity or prevent purposes aspect the medicine of smoking once again in preparation.
Being used for paroxetine of the present invention exists with the form of free alkali or its pharmaceutical salts aptly.The pharmaceutical salts of preferred paroxetine is a crystalline hydrochloride.The proper method of preparation paroxetine hydrochloride comprise United States Patent (USP) 4009196,4721723,4902801,4861893 and 5039803 and PCT/CB93/00721 in the method mentioned.Particularly preferably be semihydrate according to the EP-A-0233403 preparation.
Be used to promote to give up smoking or reduce smoking capacity or prevent the medicine of smoking once again by paroxetine or its pharmaceutical salts or hydrate being mixed with appropriate carriers can prepare, wherein carrier can comprise diluent, binding agent, filler, disintegrating agent, correctives, coloring agent, lubricant or antiseptic in a usual manner.
Preferred this medicine is a unit dosage forms, and is suitable for use in medicine or veterinary applications.For example, these preparations can be the forms of packing, have wherein added to be used to promote to give up smoking or reduce smoking capacity or prevent the hand-written of smoking once again or the explanation of printing.
The suitable dosage range of paroxetine or its pharmaceutical salts or solvate depends on smoking severity of disease and this patient's symptom.It also depends on the relation of absorption intensity and administration frequency and route of administration especially.
Paroxetine or its pharmaceutical salts or solvate can be by any approach preparation administrations, and example is oral, Sublingual, rectum, part, transdermal, non-intestinal, intravenous or intramuscular administration.If desired, preparation can be designed as the slow release form of paroxetine or its pharmaceutical salts or hydrate.These medicines can also contain promoting smoking cessation or reducing smoking capacity or prevent other favourable in the smoking method once again active constituent, as nicotine or its medicinal derivative.
For example, the powder that these medicines can be tablet, capsule, sachet, medicine bottle, powder, granule, lozenge, rebuild, perhaps liquid dosage form, for example solution or suspensoid, or suppository.
For example, those are suitable for the medicine of oral administration, can contain conventional excipients such as binding agent, for example syrup, arabic gum, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone; Filler, for example, lactose, sucrose, corn starch, calcium phosphate, sorbitol or glycerol; Tablet lubricants, for example, magnesium stearate; Disintegrating agent, for example, starch, polyvinylpyrrolidone, Explotab or microcrystalline Cellulose; Or medicinal sclerosing agent such as sodium lauryl sulphate.
Can obtain solid drugs by conventional methods such as mixing, filling, tablettings.Married operation can be used for making paroxetine or its salt or hydrate thoroughly to be distributed in the medicine that has used a large amount of filleies repeatedly.When this medicine is tablet, powder or lozenge form, can use any carrier that is suitable for preparing solid composite medicament, example has magnesium stearate, starch, glucose, lactose, sucrose, wheat flour and Chalk.Tablet coating particularly can be used enteric coating according to the method for knowing in the general medicinal practice.This medicine can also be ingestible capsule form, for example contains the gelatine capsule of paroxetine or its salt and carrier or other excipient (if desired).
The oral administration medicine of liquid form can be, for example, and Emulsion, syrup or elixir, or can exist with the form of dry products, water or other appropriate carrier rebuild before use.Such liquid medicine can contain conventional additives such as suspending agent, as sorbitol, syrup, methylcellulose, gelatin, hydroxyethyl-cellulose, carboxymethyl cellulose, stearic acid aluminium glue, hydrogenant edible fat; Emulsifying agent is as lecithin, Arlacel-60 or arabic gum; Water or nonaqueous carrier, it can comprise edible oil, for example almond oil, fractionated Oleum Cocois, oily ester such as glyceride or propylene glycol or ethanol, glycerol, water or normal saline; Antiseptic, for example methyl parahydroxybenzoate or propyl ester or sorbic acid; And conventional correctives or coloring agent (if desired).
Paroxetine or its pharmaceutical salts or solvate can also pass through non-oral administration.According to the conventional pharmaceutical method, for example, medicine can be formulated as suppository to carry out rectally.They can also be formulated as injection form moisture or non-aqueous solution, suspensoid or emulsion, and this is formulated in the medicinal fluid and carries out, for example sterile pyrogen-free water or parenterai administration oil or liquid mixture.This liquid can bacteriostatic agent, antioxidant or other antiseptic, make this solution and the isoosmotic buffer agent of blood or solute, thickening agent, suspending agent or other medical additive.These forms can exist with the form of unit dosage forms as ampoule or disposable syringe tool, or with the form of multiple dose form such as bottle (can from wherein extracting suitable dosage), maybe can be used for preparing the solid form or the concentrate of injection.
As mentioned above, the effective dose of paroxetine or its pharmaceutical salts or solvate depend on smoking severity of disease, patient's the disease for the treatment of and depend on the frequency and the approach of administration.Unit dose generally contains 2 to 1000mg and preferably contain 30 to 500mg, and particularly 20,50,100,150,200,250,300,350,400,450 or 500mg.This compositions can be administered once or repeatedly on the 1st, for example, and every day 2,3 or 4 times, and total daily dose of 70 kilograms adult generally is 100 to 3000mg.Preferred this unit dose contains about paroxetine of 2 to 20mg (calculating with free alkali) and reaches foregoing every day of dosage with (if desired) administration repeatedly.
The present invention preferably implements with controlled release or delayed release dosage forms, contains paroxetine or its pharmaceutical salts in this dosage form.
Controlled release refers to that the release of the active substance in the dosage form is changed any preparation technique that is able to than promptly releasing the slower speed generation of product (as conventional swallow tablet or capsule).
Postpone to discharge and to refer in the dosage form that the release of active substance is changed and be able to promptly to release the slower time of product and take place than routine.Discharging subsequently of active substance also can be the form of above-mentioned controlled release from delayed release preparation.
Be suitable for mixing paroxetine controlled release preparation case description in:
The slow releasing pharmaceutical treatment, Chemical Technology Review No.177, J.C.Johnson edits.Nyes?Data?Corporation?1980。
The controlled release drug transhipment, basis and application, the 2nd edition.J.R.Robinson,V.H.L.Lee.Mercel.Dekkes?Inc.New?York?1987。
Be suitable for mixing paroxetine delayed release preparation case description in:
Reminton ' s Pharmaceutical Sciences, the 16th edition, Mack PublishingCompany 1980, Ed.A.Osol.
These controlled release preparations are preferably prepared in the mode that the release of active substance such as paroxetine is mainly worked during by the harmonization of the stomach small intestinal, and delayed release preparation preferably is mixed with and makes active substance such as paroxetine avoid discharging under one's belt and mainly working during by small intestinal.
Described preparation preferably is mixed with the release mainly after absorption 1.5 to 3 hours that makes active substance.
Preferred preparation finally is enteric coated tablet or capsule sheet, the tablet of wax or polymer coating or capsule sheet or time-delay basic unit or its combination.
Particularly preferred preparation is described in the U.S. Patent No. 5102666.
Therefore, a particular aspects of the present invention relates to the purposes of polymer release-control composition, wherein contain the reaction complex that (1) Merlon calcium salt component and (2) water interact and forms in the presence of paroxetine, wherein Merlon calcium salt component is that imbibition is still water insoluble, the crosslinked carboxyl functional group polymer of fibroid, it is a plurality of at least about 80% repetitive that contains at least one carboxyl functionality that described polymer contains (a), (b) about 0.05 to about 1.5% cross-linking agent that does not have the polyalkenyl polyethers basically, described percent are respectively based on the weight of polymer repeating unit and cross-linking agent not.Merlon calcium salt amount is about 0.1 to about 99% (weight), for example, and about 10%.The amount of active substance is about 0.0001 to about 65% (weight), for example, and about 5 to 20%.The amount of water is about 5 to about 200% (weight), for example, and 5 to 10%.This interacts between pH about 3 to about 10, and for example, about 6 to 7 carry out.The calcium salt of this Merlon existed with the form of calcium salt originally, contained about 5 to about 25% calcium ion.
Further particularly preferred preparation is described in U.S. Patent No. 5422123.
Therefore, another specific aspect relates to the controlled release system of paroxetine, wherein contain (a) deposition nuclear, it contains the paroxetine of effective dose and has fixed geometric format, and the support platform of (b) providing for described deposition nuclear, wherein said deposition nuclear contains paroxetine, and at least a following component (1) that is selected from is at contact water or expansible polymer and can form the polymer of gel when liquid, aqueous, wherein said expandable polymer and the described ratio that can form the polymer of gel are 1: 9 to 9: 1, and (2) have expansion and the single polymers that becomes gelling properties simultaneously, and described support platform is an elastic supporter, it is applied to described deposition nuclear, so that its part covers deposition nuclear surface and changes with deposition nuclear hydration, and slowly dissolving and/or slowly form gel in liquid, aqueous.This support platform can contain polymer such as hydroxypropyl methylcellulose, plasticizer such as glyceride, binding agent such as polyvinylpyrrolidone, hydrophilic reagent such as lactose and silica gel and/or hydrophobic agents such as magnesium stearate and glyceride.This polymer (one or more) generally accounts for 30 to 90% of this support platform weight, for example, and about 35 to 40%.Plasticizer can account at least 2% of this support platform weight, for example, and about 15 to 20%.General maximum the about 50% of this support platform weight that account for altogether of binding agent (one or more), hydrophilic reagent (one or more) and hydrophobic agents (one or more), for example, about 40 to 50%.
The present invention also provides and has been used to promote to give up smoking or reduces smoking capacity or prevent the pharmaceutical composition of smoking once again, wherein contains paroxetine or its pharmaceutical salts or the solvate and the pharmaceutical carrier of effective dose.These compositionss mode as described above prepare.
Paroxetine product of the present invention can be optionally and smoking cessation auxiliary agent that contains nicotine such as the administration simultaneously of subsides, glue or inhalant.
The following example has been described and has been used for suitable drugs compositions of the present invention.
%w/w in embodiment 1 (hydrophilic skeleton) granule
Paroxetine hydrochloride 11.45
Hydroxypropyl methylcellulose (Methocel) E5 1.25
Outside lactose 12.3 granules
Hydroxypropyl methylcellulose K100LV 30.0
Lactose 44.0
Magnesium stearate 1.0
Amount to 100.0
%w/w in embodiment 2 (hydrophilic skeleton) granule
Paroxetine hydrochloride 11.45
Hydroxypropyl methylcellulose (Methocel) E5 1.25
Outside lactose 12.3 granules
Hydroxypropyl methylcellulose K100LV 27.5
Hydroxypropyl methylcellulose K4M 7.5
Lactose 39.0
Magnesium stearate 1.0
Amount to 100.0
Embodiment 3 (promptly releasing the responsive coating of pH on the nuclear core) tablet core core %w/w
Paroxetine hydrochloride 11.45
Lactose 64.05
Microcrystalline Cellulose 20.0
Explotab 4.0
Magnesium stearate 0.5
Amount to 100.0 tablet coatings (consumption accounts for the 6-10% of tablet core core weight) %w/w hydroxypropyl methylcellulose phthalate, 90.0 glycerol triacetates 10.0
Embodiment 4 (promptly releasing the responsive coating of pH on the nuclear core)
Tablet core core such as embodiment 3
Tablet coating (consumption accounts for the 6-10% of tablet core core weight) %w/w
Cellulose acetate phthalic acid ester 90.0
Diethyl phthalate 10.0
Embodiment 5 (promptly releasing the controlled release coat on the nuclear core)
Tablet core core such as embodiment 3 tablet coatings (consumption accounts for the 5-12% of tablet core core weight) %w/w acrylic emulsion (Eudragit) RS 100 86.0 dibutyl phthalates 10.0 Talcum 4.0FD﹠amp; The yellow No.6 0.01 of C
Embodiment 6 (the responsive coating of pH on the controlled release nuclear core)
Tablet core core such as embodiment 3
Tablet coating such as embodiment 3
Embodiment 7 (the controlled release coat beadlet of sealing)
Microgranule %w/w (pact)
Non-sugar nuclear 30
Paroxetine hydrochloride 40
Gelatin 8
Lactose 20
Talcum 2
Coating %w/w
Glyceryl monostearate 36.6
Glycerol distearate 53.4
White beeswax 10.0
Embodiment 8 (controlled release bilayer tablet)
The active hydroxypropyl methylcellulose K4M of active layer component mg/ sheet function paroxetine hydrochloride 22.89* 15.00 aquogel polymer lactose monohydrates 62.0 hydrophilic reagent polyvinylpyrrolidones 3.0 binding agent magnesium stearate 1.0 hydrophobic agents Syloid 244 1.0 hydrophilic reagents
Support platform
Component mg/ sheet function
Compritol 888 15.04 plasticizers
Lactose monohydrate 29.32 hydrophilic reagents
Polyvinylpyrrolidone 4.0 binding agents
Magnesium stearate 1.52 hydrophobic agents
Hydroxypropyl methylcellulose E5 29.32 aquogel polymers
Ferrum oxide 0.08 coloring agent
Total tablet weight 184.89mg
* be equivalent to 20mg paroxetine free alkali.
With every layer powder wet granulation and dry in fluid bed dryer in high-shear mixer/granulator.This bilayer tablet of compacting on Manesty three laminate machines.
Embodiment 9 (the Merlon calcium salt preparation of enteric coating)
The nuclear core
Component mg/ sheet function
Paroxetine hydrochloride 22.89* activity
Merlon calcium salt 20.00 skeletons
Lactis Anhydrous 146.11 hydrophilic reagents/diluent
Polyvinylpyrrolidone 10.0 binding agents
Magnesium stearate 1.0 hydrophobic agents/lubricant
Water * * 0.024 granulation liquid
Enteric coating
Component mg/ sheet function
Acrylic emulsion 22.19 polymer
Talcum 1.53 lubricants
Triethyl citrate 1.00 plasticizers
Water * * 24.6 diluent
The film coating
Opadry pink 10.5 film coatings
Water * * 94.5 diluent
The polishing coating
Opadry?clear 0.750
Water * * 29.3 diluent
* be equivalent to 20mg paroxetine free alkali.
The * work in-process is removed.
With the active constituent wet granulation, and dry in fluid bed dryer in high-shear mixer/granulator.Add magnesium stearate then and in low shear mixer, handle.Then, on the Type B rotary tablet machine with this mixture tabletting.Carry out coating with Accela cota.
Embodiment 10 (controlled release bilayer tablet)
The active hydroxypropyl methylcellulose K4M of active layer component mg/ sheet function paroxetine hydrochloride 22.89* 20.00 aquogel polymer lactose monohydrates 60.0 hydrophilic reagent polyvinylpyrrolidones 5.0 binding agent magnesium stearate 1.0 hydrophobic agents Syloid 244 1.0 hydrophilic reagents
The total tablet weight 189.89mg of support platform component mg/ sheet function Compritol 888 14.72 plasticizer lactose monohydrate 30.60 hydrophilic reagent polyvinylpyrrolidones, 2.80 binding agent magnesium stearate 0.80 hydrophobic agents hydroxypropyl methylcellulose E5,30.60 aquogel polymer Syloid 244 0.40 hydrophilic reagent ferrum oxides, 0.08 coloring agent
* be equivalent to 20mg paroxetine free alkali.
Method for making is as described in the embodiment 8.
Embodiment 11 (controlled release bilayer tablet)
The active hydroxypropyl methylcellulose K4M of active layer component mg/ sheet function paroxetine hydrochloride 22.89* 15.00 aquogel polymer lactose monohydrates 63.31 hydrophilic reagent polyvinylpyrrolidones 2.0 binding agent magnesium stearate 1.0 hydrophobic agents Syloid 244 0.40 hydrophilic reagents
Support platform-as embodiment 10.
Total tablet weight 184.60mg
* be equivalent to 20mg paroxetine free alkali.
Method for making such as embodiment 8.
Embodiment 12 (enteric coating controlled release bilayer tablet)
The active hydroxypropyl methylcellulose K4M of active layer component mg/ sheet function paroxetine hydrochloride 28.61* 18.75 aquogel polymer lactose monohydrates 79.14 hydrophilic reagent polyvinylpyrrolidones 2.50 binding agent magnesium stearate 1.25 hydrophobic agents Syloid 244 0.50 hydrophilic reagents
Support platform component mg/ sheet function Compritol 888 15.04 plasticizer lactose monohydrates 30.50 hydrophilic reagent polyvinylpyrrolidones 4.00 binding agent magnesium stearate 0.80 hydrophobic agents hydroxypropyl methylcellulose E5 29.32 aquogel polymer Syloid 244 0.32 hydrophilic reagent ferrum oxides 0.02 coloring agent
The total tablet weight 228.66mg of enteric coating component mg/ sheet function acrylic emulsion 13.27 polymer Talcum 3.31 lubricant triethyl citrates, 1.33 plasticizer water * * 36.25 diluent
* be equivalent to 25mg paroxetine free alkali.
The * work in-process is removed.
Method for making such as embodiment 9.
Embodiment 13
According to conventional method with following component mix and suppress attach most importance to about 300mg, contain the tablet of 20mg paroxetine (calculating) with free alkali.The total tablet weight 3000.0g of paroxetine hydrochloride hemihydrate compound 228.8g dicalcium phosphate dihydrate 2441.2g hydroxypropyl methylcellulose 2910 150.0g Explotab 150.0g magnesium stearate 30.0g

Claims (9)

1. promote smoking cessation or reduce smoking capacity or prevent the method for smoking once again that this method comprises that the people to needs uses paroxetine or its pharmaceutical salts or solvate effective, nontoxic amount.
2. paroxetine or its pharmaceutical salts or solvate are used for promoting giving up smoking or reduce smoking capacity or prevent the purposes of the medicine of smoking once again in preparation.
3. the purposes of claim 2, wherein paroxetine is the form of free alkali or its pharmaceutical salts.
4. the purposes of claim 3, wherein the pharmaceutical salts of paroxetine is a crystalline hydrochloride.
5. the purposes of claim 4, wherein hydrochlorate is a semihydrate.
6. each purposes of claim 2 to 5, wherein paroxetine is with the mode administration of controlled release or delayed release preparation.
7. the purposes of claim 6, wherein paroxetine is an oral administration.
8. the purposes of claim 7, wherein controlled release or delayed release preparation contain (a) deposition nuclear, it contains the paroxetine of effective dose and has fixed geometric format, and the support platform of (b) providing for described deposition nuclear, wherein said deposition nuclear contains paroxetine, and at least a following component (1) that is selected from is at contact water or expansible polymer and can form the polymer of gel when liquid, aqueous, wherein said expandable polymer and the described ratio that can form the polymer of gel are 1: 9 to 9: 1, and (2) have expansion and the single polymers that becomes gelling properties simultaneously, and described support platform is an elastic supporter, it is applied to described deposition nuclear, so that its part covers deposition nuclear surface and changes with deposition nuclear hydration, and slowly dissolving and/or slowly form gel in liquid, aqueous.
9. each purposes of claim 2 to 8, wherein paroxetine and the together administration of smoking cessation auxiliary agent that contains nicotine.
CN99807465A 1998-06-16 1999-06-16 Method of treatment Pending CN1305379A (en)

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AU2001296084A1 (en) * 2000-08-28 2002-03-13 Synthon B.V. Paroxetine compositions and processes for making the same
IL162666A0 (en) 2001-12-28 2005-11-20 Teva Pharma A stable pharmaceutical formulation of paroxetine hydrochloride and a process for preparation thereof
US20060039975A1 (en) * 2004-08-20 2006-02-23 Zalman Vilkov Paroxetine formulations
FR2926221A1 (en) * 2008-01-14 2009-07-17 Tassin Thomas COMPOSITIONS FOR THE ARTIFICIAL REPRODUCTION OF THE PHARMACOLOGICAL CONDITIONS OF ADDICTIVE DRUG DEPENDENCE SUCH AS OPIACES, PSYCHOSTIMULANTS, TOBACCO AND ALCOHOL, BY COMBINING NICOTINE AND A LIGAND.

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EP0223403B1 (en) * 1985-10-25 1993-08-04 Beecham Group Plc Piperidine derivative, its preparation, and its use as medicament
CA2096853A1 (en) * 1990-11-24 1992-05-25 Anthony Michael Johnson Use of paroxetine for the treatment of senile dementia, bulimia, migraine or anorexia
AR001982A1 (en) * 1995-02-06 1998-01-07 Smithkline Beecham Plc PAROXETINE CHLORHYDRATE ANHYDRATED, AND PROCEDURE FOR ITS PREPARATION
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EA200100041A1 (en) 2001-06-25
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AP2000002002A0 (en) 2000-12-31
ZA200007396B (en) 2002-02-27
IL139943A0 (en) 2002-02-10
GB9812941D0 (en) 1998-08-12
EA003584B1 (en) 2003-06-26
JP2002518330A (en) 2002-06-25
KR20010052895A (en) 2001-06-25
HUP0102507A2 (en) 2002-05-29
CZ20004698A3 (en) 2002-02-13
AU4688599A (en) 2000-01-05
EP1087766A1 (en) 2001-04-04
PL345261A1 (en) 2001-12-03
EP1087766A4 (en) 2001-11-21
HUP0102507A3 (en) 2003-12-29
NZ508532A (en) 2003-08-29
NO20006383L (en) 2000-12-14
CA2335236A1 (en) 1999-12-23
BR9911150A (en) 2001-03-06
BG105127A (en) 2001-11-30
AU740749B2 (en) 2001-11-15
SK19192000A3 (en) 2001-05-10

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