EP2029097A2 - Comprimé plat combinée d'antidépresseurs - Google Patents

Comprimé plat combinée d'antidépresseurs

Info

Publication number
EP2029097A2
EP2029097A2 EP07725804A EP07725804A EP2029097A2 EP 2029097 A2 EP2029097 A2 EP 2029097A2 EP 07725804 A EP07725804 A EP 07725804A EP 07725804 A EP07725804 A EP 07725804A EP 2029097 A2 EP2029097 A2 EP 2029097A2
Authority
EP
European Patent Office
Prior art keywords
preparation according
derivatives
pharmaceutical preparation
active ingredient
active
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP07725804A
Other languages
German (de)
English (en)
Inventor
Hans-Rainer Hoffmann
Reto BRÄNDLI
Frank Theobald
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LTS Lohmann Therapie Systeme AG
Original Assignee
LTS Lohmann Therapie Systeme AG
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
Application filed by LTS Lohmann Therapie Systeme AG filed Critical LTS Lohmann Therapie Systeme AG
Publication of EP2029097A2 publication Critical patent/EP2029097A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics

Definitions

  • the present invention relates to surface-shaped, rapidly disintegrating on contact with moisture, drug preparation based on hydrophilic polymers for release of at least one active ingredient in a body orifice or body cavity, wherein the dosage form contains a drug combination for depression therapy and at least one of the active compounds from the group of Antidepressants is selected.
  • the invention further relates to the use of such an active ingredient combination for the preparation of an orally administrable medicament for the treatment of depression, as well as the therapeutic treatment of depression by oral administration of one of the said medicament preparations.
  • depressive disorders are susceptible to drug therapy, whereby the therapeutic approach is to restore the disturbed balance. This can be achieved either by increasing the concentration of the neurotransmitters or by improving the neurological signal transmission.
  • therapy with a suitably selected antidepressant drug tailored to the condition of the patient is often sufficient.
  • Another problem of the therapy is to ensure the intake of prescribed medication, since the mental health of the patients is often so bad that they forget the intake, the patients often feel healthy and in their opinion the medication is not needed, or the Patients distrust the medication and refuse to take it, eg in that tablets are collected in the mouth and spat out.
  • Common dosage forms for administration of drugs in therapy are tablets or capsules.
  • buccal or sublingual tablets which release the active substance in the oral cavity, so that it can be absorbed directly through the oral mucosa.
  • the object underlying the invention was therefore to provide pharmaceutical preparations with which a combination therapy for the treatment of depressive disorders in a simple and safe manner is feasible, and which make it possible to avoid or reduce the above-mentioned disadvantages.
  • the invention was also based on the object of demonstrating methods for the drug combination therapy of depressive diseases.
  • the improved therapeutic success of a drug combination in the treatment of depression is due to ren that different drugs act through different mechanisms, which often also the dose - and thus the ADR - of the individual drug can be reduced.
  • the combination therapy may also treat different symptoms of depression or associated mental disorders that an active ingredient alone does not cover.
  • orally administrable dosage forms represent a suitable means.
  • wafers flat-shaped pharmaceutical preparations in the form of wafer-like administration forms, which are referred to as "wafers", wherein the wafers based on hydrophilic polymers rapidly disintegrate on contact with moisture and at least one active ingredient Immediate release of active ingredient combination, which is at least partially absorbed transmucosally, wherein at least one of the active ingredients of the active ingredient combination is selected from the group of antidepressants.
  • the use of a combination of active ingredients with at least one antidepressant and another psychotropic agent is suitable for the production of a wafer for the treatment of depression.
  • the orally administered dosage form as a wafer from a rapidly disintegrating hydrophilic polymer the intake of the drugs is ensured by the patient, as it disintegrates immediately in the mouth.
  • an active ingredient combination adapted to the therapy already exists, so that the administration of the medicament only has to be monitored once.
  • the at least partial absorption of the active ingredients via the oral mucosa offers the advantages over other peroral forms of administration that even patients with dysphagia or patients who refuse to take tablets can receive medication orally.
  • the active ingredients are not subject to the first-pass effect. Since in this way no active ingredient is metabolized before reaching the site of action, the initial dosage can be kept as low as possible. Furthermore, fluctuations in the active ingredient concentration are suppressed or minimized by incomplete or delayed absorption and delayed action as a function of the amount of food previously ingested. The adjustment of the patient can thus be made more reliable and the need, for example, an intake on an empty stomach can be omitted.
  • active ingredients with different mechanisms of action may be present in a combination of active ingredients which act synergistically, so that smaller quantities of the active ingredients can be added due to the different physiological action and treatment of different symptoms of depression than would be the case with one-component compositions.
  • active ingredients with different mechanisms of action may be present in a combination of active ingredients which act synergistically, so that smaller quantities of the active ingredients can be added due to the different physiological action and treatment of different symptoms of depression than would be the case with one-component compositions.
  • Both combinations of different antidepressants and combinations of one or more antidepressants and anxiolytics, tranquilizers, nootropics, neuroleptics, sympathomimetics with psychoanaleptic action, antiarrhythmics, sedatives and / or benzodiazepines can be used here.
  • the wafers may therefore contain up to five, preferably up to three, and particularly preferably two active ingredients, wherein at least one of these active ingredients is an antidepressant.
  • the dosages can be adapted to the respective needs.
  • the ratio of the active ingredients to one another can be adapted to the respective needs.
  • the symptoms of depression e.g. Only a light or low-dose antidepressant be administered while a corresponding sedative or benzodiazepine is given to combat a strong restlessness.
  • drugs can be combined in appropriate proportions so that various symptoms of depression are given priority.
  • the wafer is made of a laminate, then during production e.g. only the layer thickness of a drug-containing layer or the concentration of the active ingredient can be changed.
  • drugs with different active ingredient content but the same active ingredient ratio can be easily prepared via different area blanks of the dosage form.
  • one of the active ingredients may be effective immediately, while a second active ingredient, for example, has a shorter half-life, has a retarding effect. Due to the delayed continuous release, the plasma concentrations of the active ingredients remain constant over a longer period of time.
  • the wafers according to the invention can easily be carried with the active substance combinations because of their flat form, e.g. in the wallet, and are also immediately available on the way, easy to take and fast acting, both in the regular therapy, as well as in sudden attacks, e.g. Panic attacks, anxiety and the like.
  • water-soluble or swellable polymers for the hydrophilic water-soluble and / or swellable polymer film are suitable as the base polymer polymers from the group, the dextran, polysaccharides, including the starch and
  • Starch derivatives such as carboxymethylcellulose loose, ethyl or propylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose (eg Walocel), methylcellulose,
  • polyvinyl alcohols polyethylene glycols
  • polyacrylic acids polyacrylates
  • polyvinylpyrrolidones alginates
  • pectins gelatin, alginic acid, collagen, chitosan, arabinogalactan, galactomannan, agar-agar, agarose, carrageenan natural gums, tragacanth, fumed silica, bentonite , and derivatives of the aforementioned hydrophilic polymers or combinations of two or more of these polymers.
  • the polymer film may also be made of a polyvinyl alcohol-polyethylene glycol graft copolymer.
  • the polymer content of a dosage form according to the invention is preferably from 5 to 95% by weight, more preferably from 15 to 75% by weight, based on the dry weight of the dosage form.
  • Suitable antidepressants for use in a combination wafer include the tricyclic, tetracyclic and noncyclic antidepressants and the general active ingredient groups of phenothiazines, azaphenothiazines, thioxanthenes, butyrophenones, diphenylbutylpiperidines, imidibenzyl derivatives, iminostilbene derivatives,
  • Dibenzocycloheptadiene derivatives dibenzodiazepine derivatives, dibenzoxepine derivatives, benzodiazepines, indole derivatives, phenylethylamine derivatives and hypericin derivatives and pharmaceutically acceptable salts or derivatives of these compounds.
  • SSRI serotonin reuptake inhibitors
  • Selected drugs of these groups of antidepressants are e.g. Amitryptiline, Amitrytilinoxide, Buspirone, Citalopram, Clomipramine, Desipramine, Dibenzepine, Dosulepin, Doxepin, Fluoxetine, Fluvoxamine, Imipramine, Lofepramine, Maprotiline, Mianserin, Mirtazapine, Moclobemide, Nefazodone, Nortryptiline, Opipramol, Oxitriptan, Paroxetine, Reboxetine, Sertraline, Tranylcypromine, Trimipramine, venlafaxine and viloxazine as well as pharmaceutically acceptable salts of these drugs.
  • Amitryptiline Amitrytilinoxide
  • Buspirone Citalopram
  • Clomipramine Desipramine
  • Desipramine Desipramine
  • Dibenzepine Dosulepin
  • Doxepin Doxepin
  • Also suitable for the therapy of depression are the abovementioned groups of active ingredients of the anxiolytics, tranquilizers, nootropics, neuroleptics, sympathomimetics with psychoanaleptic action, antiarrhythmics, sedatives and benzodiazepines, and the active substances selected from these groups, such as caffeine, meprobamate, reserpine, Prolintan, hydroxyzine, lorazepam, chlorpromazine, clozapine, perphenazine, risperidone, sulpiride, meclofenoxate, nicergoline, piracetam, pyritinol, fenetyllin and methylphenidate and the pharmaceutically acceptable salts of these drugs.
  • active ingredients of the anxiolytics such as caffeine, meprobamate, reserpine, Prolintan, hydroxyzine, lorazepam, chlorpromazine, clozapine, perphena
  • the active compound combinations according to the invention contain at least one antidepressant and optionally one or more further active ingredients of the other active ingredient groups.
  • at least one drug is a selective serotonin reuptake inhibitor (SSRI) such as fluoxetine or paroxetine.
  • SSRI selective serotonin reuptake inhibitor
  • the active substance combination consists of mirtazapine and lorazepam or their pharmacologically acceptable salts, the ratio of mirtazapine to lorazepam being 95% -80% to 5% -20%, preferably 88% -12%.
  • the active ingredient combination comprises three active ingredients, mirtazapine, lorazepam and risperidone or their pharmacologically acceptable salts, wherein the ratio of mirtazapine to lorazepam to riserone is preferably 75% to 10% to 15%, but other compositions are possible.
  • Another preferred active ingredient combination consists of the anxiolytic buspirone and trancylpromine, reboxetine or mirtazapine.
  • the active ingredient combination comprises the anxiolytic buspirone and lorazepam, the ratio of buspirone to lorazepam being 95% -80% to 5% -20%, preferably 88% -12%.
  • moisturizers may be added to the film, for example glycerol, propylene glycol, sorbitol, mannitol, polyethylene glycol, polyglycerol esters and the like.
  • antioxidants may be added to the wafer to stabilize the film and the active agents, e.g. Vitamin C (ascorbic acid), ascorbyl palmitate, vitamin E (tocopherol acetate), hydroxybenzoic acid derivatives.
  • active agents e.g. Vitamin C (ascorbic acid), ascorbyl palmitate, vitamin E (tocopherol acetate), hydroxybenzoic acid derivatives.
  • acidic and basic ion exchangers can also be used as stabilizers.
  • further ingredients such as dyes, pigments, flavorings, natural and / or synthetic flavorings, sweeteners, buffering systems may be added to the film. Flavors and aromas in particular can mask the often bad taste or smell of the active ingredients and / or give the dosage form a pleasant taste, so that the willingness to take the medication by the patient is significantly improved.
  • the active ingredient (s) of the preparation may also be bound to an acidic or basic ion exchanger for taste masking.
  • buffering systems serves, on the one hand, to stabilize the film and the active ingredients against external influences and during storage, and on the other hand, it is possible to adjust the pH of the administration form to a physiologically acceptable pH, so that mucous membrane irritation can be achieved. be avoided.
  • a buffer system can also improve the solubility of acidic or basic drugs in the matrix.
  • the administration forms according to the invention are thin, for example in the form of a wafer.
  • the thickness of the dosage form is preferably 0.1 to 5 mm, more preferably 0.5 to 1 mm.
  • the lower limit for the thickness of the dosage forms is about 50 ⁇ m.
  • the area of the dosage form is between 0.09 cm 2 and 12 cm 2 , preferably between 1 cm 2 and 8 cm 2 , and particularly preferably between 3 cm 2 and 6 cm 2 .
  • the wafers of the present invention include a disintegrant or wicking agent, e.g. a bicarbonate-acid mixture or an aerosil, which is activated by contact with liquid and accelerates the disintegration of the wafer after application and thus also the release of active ingredient.
  • a disintegrant or wicking agent e.g. a bicarbonate-acid mixture or an aerosil
  • the wafer is present as a foam, so that the Wirkstoffabgäbe due to the increased surface area is even faster.
  • one or more of the active ingredients or auxiliaries may be in liquid form in the cavities of the foam.
  • permeation promoters for example substances from the groups of the fatty alcohols, fatty acids, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty acid oils.
  • esters, fatty alcohol esters and fatty acid esters in particular sorbitan monolaurate or esters of long-chain fatty acids with methyl, ethyl or isopropyl alcohol, or esters of fatty alcohols with acetic acid or lactic acid, or else substances such as DMSO (dimethyl sulfoxide) and oleic diethanolamine.
  • the proportion of these substances if present, 0.1 wt .-% to 25 wt .-%, preferably from 1 wt .-% to 10 wt .-%, each based on the total weight of the active ingredient matrix.
  • composition of the wafer may contain compounds that retard drug release (e.g., microencapsulation).
  • the wafer has mucoadhesive properties so that it adheres to the mucous membrane until it is completely dissolved.
  • This embodiment additionally facilitates the monitoring of the administration of the medicaments since the wafer adhering to the mucous membrane can not be spit out.
  • At least one of the active ingredients is bound to an ion exchanger, so that the hydrophilic polymer disintegrates rapidly in the oral cavity, but the release of the active ingredient only delayed or at a changed pH, for example in the gastrointestinal tract occurs.
  • active ingredients with different mechanisms of action and absorption can be administered in one dosage form, ie at least one of the released active substances is resorbed at the application site. beer, z. B. on the oral mucosa, and the other is transported and resorbed at another location.
  • the wafer can also be constructed as a laminate with different layers, wherein the active ingredients are contained in discrete layers, which are spatially separated from each other and differ in their construction.
  • the active ingredients can be released at different sites of action or else delayed, if the disintegration time of the different layers of the wafer differs.
  • the active ingredients may be arranged in layers which disintegrate at different rates so that the entire preparation has a sustained-release effect.
  • only one of the outer layers may be mucoadhesive to promote adherence of the dosage form to the mucosa and to facilitate the drug resorption through the mucosa through direct contact.
  • Decay in aqueous medium of the dosage form of the invention is preferably in the range of 1 second to 5 minutes, more preferably in the range of 5 seconds to 1 minute, and most preferably in the range of 10 seconds to 30 seconds.
  • administration forms according to the invention are advantageously suitable for administering medicaments in the oral cavity or for rectal, vaginal or intravenous administration. nasal administration. They can be used in human medicine as well as in veterinary medicine.
  • the present invention is further directed to the use of one of the active ingredient combination according to the invention for the preparation of an oral dosage form for the treatment of depressive disorders, wherein the dosage form is preferably formulated as a wafer.
  • the present invention is directed to a method for the therapeutic treatment of a person suffering from depression, wherein the administration of a previously described drug combination of antidepressants by means of an orally administered dosage form with at least partial transmucosal absorption of at least one active ingredient.
  • the present invention is also directed to a method for producing a sheet-like dosage form, which comprises the following steps:

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Psychiatry (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Cardiology (AREA)
  • Anesthesiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne des compositions d'agents pharmaceutiques planes, se décomposant rapidement au contact de l'humidité, à base de polymères hydrophiles, pour la libération d'au moins un agent actif. La forme galénique contient une combinaison d'agents actifs pour la thérapie de la dépression et au moins un des agents actifs est choisi parmi le groupe d'antidépresseurs. L'invention concerne en outre l'utilisation d'une telle combinaison d'agents actifs pour la préparation d'un agent pharmaceutique, administrable par voie orale, pour le traitement de la dépression, ainsi que le traitement thérapeutique de la dépression par administration orale d'une des compositions d'agents pharmaceutiques citées.
EP07725804A 2006-06-16 2007-06-04 Comprimé plat combinée d'antidépresseurs Withdrawn EP2029097A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102006027792A DE102006027792A1 (de) 2006-06-16 2006-06-16 Antidepressiva-Kombinations-Wafer
PCT/EP2007/004936 WO2007144080A2 (fr) 2006-06-16 2007-06-04 Comprimé plat combinée d'antidépresseurs

Publications (1)

Publication Number Publication Date
EP2029097A2 true EP2029097A2 (fr) 2009-03-04

Family

ID=38667454

Family Applications (1)

Application Number Title Priority Date Filing Date
EP07725804A Withdrawn EP2029097A2 (fr) 2006-06-16 2007-06-04 Comprimé plat combinée d'antidépresseurs

Country Status (7)

Country Link
US (1) US20090203670A1 (fr)
EP (1) EP2029097A2 (fr)
JP (1) JP2009539892A (fr)
CN (1) CN101460145A (fr)
CA (1) CA2652476A1 (fr)
DE (1) DE102006027792A1 (fr)
WO (1) WO2007144080A2 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2252261A2 (fr) * 2008-02-13 2010-11-24 Bayer Schering Pharma Aktiengesellschaft Système d'administration de médicament présentant un effet stabilisateur
BRPI0908477A2 (pt) * 2008-02-13 2018-03-27 Bayer Schering Pharma Ag sistema de distribuição de medicamento contendo estradiol
CN101966151B (zh) * 2010-09-06 2011-11-09 海南美大制药有限公司 马来酸曲米帕明脂质体固体制剂
US9687445B2 (en) 2012-04-12 2017-06-27 Lts Lohmann Therapie-Systeme Ag Oral film containing opiate enteric-release beads
WO2016138357A1 (fr) 2015-02-27 2016-09-01 Kindred Biosciences, Inc. Stimulation de l'appétit, gestion de la perte de poids, et traitement de l'anorexie chez les chiens et les chats
CN106729652A (zh) * 2016-11-30 2017-05-31 郑州仁宏医药科技有限公司 一种治疗抑郁症的西药组合物及其制备方法
JP7704193B2 (ja) * 2021-03-29 2025-07-08 日本電気株式会社 学習装置、判定装置、学習済みモデル生成方法及びプログラム

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Publication number Priority date Publication date Assignee Title
DE19960154A1 (de) * 1999-12-14 2001-07-12 Lohmann Therapie Syst Lts Flache Arzneizubereitung zur transmucosalen Verabreichung von Oxycodon oder einem vergleichbaren Wirkstoff in der Mundhöhle, für die Anwendung in der Schmerztherapie und Suchttherapie
DE10018834A1 (de) * 2000-04-15 2001-10-25 Lohmann Therapie Syst Lts Transdermale oder transmucosale Darreichungsformen mit einer nicotinhaltigen Wirkstoffkombination zur Raucherentwöhnung
DE10207394B4 (de) * 2002-02-21 2007-03-29 Lts Lohmann Therapie-Systeme Ag Geschmacksmaskierte oblatenförmige Arzneizubereitung
BR0302017B1 (pt) * 2003-06-02 2014-10-29 Ems Sigma Pharma Ltda Composição farmacêutica sublingual a base de um agonista do receptor central de benzodiazepínicos
DE10328942A1 (de) * 2003-06-27 2005-01-27 Lts Lohmann Therapie-Systeme Ag Transmukosale Darreichungsformen mit verminderter Schleimhautirritation
DE10354894A1 (de) * 2003-11-24 2005-07-07 Hf Arzneimittelforschung Gmbh Orale Formulierungen des Desoxypeganins und deren Anwendungen

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007144080A2 *

Also Published As

Publication number Publication date
WO2007144080A2 (fr) 2007-12-21
CA2652476A1 (fr) 2007-12-21
DE102006027792A1 (de) 2007-12-20
CN101460145A (zh) 2009-06-17
US20090203670A1 (en) 2009-08-13
JP2009539892A (ja) 2009-11-19
WO2007144080A3 (fr) 2008-04-24

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