Classifications

• • 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
  • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
  • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
  • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
  • A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• • 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
  • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
  • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• • 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
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• • 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
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
  • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• • 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
  • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
  • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
• • 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
  • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
  • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
  • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
• • 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
  • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
  • A61K9/0007—Effervescent
• • 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
  • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• • 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
• • 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
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/20—Hypnotics; Sedatives

Definitions

• the present invention relates to a pharmaceutical composition for oral administration, intended to avoid the misuse of use at the expense of a third party.
• the active ingredients which can be included in the pharmaceutical compositions according to the present invention belong to the therapeutic classes exposed to the risk of misuse.
• the following classes of active principles may be mentioned: analgesics, anxiolytics or hypnotics.
• methadone among the weak opioid analgesics codeine and its derivatives, dextropropoxyphene, tramadol
• the mixed opioid analgesics the morphine agonists / antagonists such as buprenorphine or pentazocine, morphine and morphinomimetics such as phethidine, dextromoramide, oxycodone, fentanyl and tamgesic.
• anxiolytic compounds mention may be made of diazepam, medazepam, oxazepam, lorazepam, benzodiazepines, eprobamate, ydroxyzine, buspirone.
• Hypnotic compounds can belong to all therapeutic classes, whether short or long acting, for example: - compounds of the benzodiazepine class recognized for their hypnotic activity such as triazolam, loprazolam, nitrazepam, lormetazepam, temazepam, estazolam, flunitrazepam, brotizolam, cinolazepam, haloxazolam, doxefazepam and their pharmacologically acceptable salts, for example loprazolam mesilate, - zopiclone and in particular (R) -zopiclone of the therapeutic class cyclopyrrolones,
• zolpidem hemitartrate
• the object of the present invention is to provide a pharmaceutical composition intended for oral administration, comprising an active principle exposed to the risk of misuse or a pharmaceutically acceptable salt thereof, capable of both:
• compositions according to the present invention are of acceptable size for conventional oral administration. Thus, compositions with a weight of less than 800 mg will be preferred.
• compositions according to the present invention can be in the form of a conventional tablet (monolayer), of a multilayer tablet, in particular of 2 or 3 layers or also in the form of conventional capsules (containing powder) or comprising microgranules or sachets comprising powder or granules.
• a conventional tablet monolayer
• a multilayer tablet in particular of 2 or 3 layers
• conventional capsules containing powder
• microgranules or sachets comprising powder or granules.
• two of the layers may contain two different active ingredients independently of each other.
• the term “visual means” means any element indicating the presence of the composition according to the invention in an aqueous alcoholic beverage which may be alcoholic and which may take the form, for example, of a dye, a flotation of the composition on the surface of the drink, of a formation of insoluble particles on the surface of the drink, on the edges of the container, in the drink and on the bottom of the container.
• the optionally alcoholic aqueous beverage may in particular consist of coffee, tea, wine, spirits, hot or cold chocolate drinks, hot or cold milk, any soda such as Coca Cola ®, any carbonated alcoholic drink or not, any cocktail or liquid mixture based on fruit juice, milk or cream, alcohols ...
• the present invention is a pharmaceutical composition
• a pharmaceutical composition comprising an active principle exposed to the risk of misuse or one of its salts, characterized in that it is in the form of a tablet intended for administration by the oral and endowed with means. visuals which are put in place after introduction into an optionally alcoholic beverage, consisting either in the flotation of the tablet, or in the formation of insoluble particles or in a combination of these two visual means.
• the buoyancy of the tablet can be ensured by an effervescence which can be obtained by means of an effervescence generator, as described below.
• the tablet may have viscosity properties appearing in contact with any drink. This last characteristic allows trapping of the gas produced by the effervescence which also results in swelling of the tablet. The drop in density generated then makes it possible to maintain the tablet on the surface of the drink.
• Such viscosity can be obtained by one or more gelling compounds.
• the viscosity measured according to the method described in point 3.3 of Example 3 can vary from 1500 to 6000 mPa.s.
• hydrophilic excipients which are suitable as a gelable compound.
• the particles can be obtained by the combination of a lipophilic excipient with a hydrophilic excipient useful for flotation, as described above.
• a lipophilic excipient with a hydrophilic excipient useful for flotation, as described above.
• a list of suitable lipophilic excipients is given below.
• the tablet may release visible insoluble particles even if the tablet does not float or does not immediately float.
• a preferred embodiment of the invention is therefore a pharmaceutical composition
• a pharmaceutical composition comprising an active principle exposed to misuse or a salt thereof, characterized in that it is in the form of a tablet intended for administration orally, capable of floating and forming particles insoluble in any liquid into which it is introduced and containing one or more generators of effervescence and one or more gelling compounds.
• the effervescence generator can be in the form of an effervescent couple, consisting of a carbon dioxide generating agent and a pharmaceutically acceptable acid compound.
• the carbon dioxide generating agent is usually a carbonate or bicarbonate of an alkali metal, an alkaline earth or an amino acid. Mention may be made, for example, as carbon dioxide generating agent, calcium carbonate, sodium bicarbonate, potassium bicarbonate, potassium carbonate, L-lysine carbonate, arginine carbonate or sodium sesquicarbonate.
• the pharmaceutically acceptable acid compound is an acid anhydride, a monocarboxylic acid, a polycarboxylic acid or a partial salt of polycarboxylic acid.
• the pharmaceutically acceptable acid compound can be chosen more particularly from citric acid, tartaric acid, ascorbic acid, fumaric acid, nicotinic acid, acetylsalicylic acid, malic acid, adipic acid. , succinic acid, glutaric anhydride, citric anhydride, maleic acid, malonic acid, monosodium citrate and succinic anhydride.
• the carbon dioxide generating agent can consist of a mixture of several carbon dioxide generating agents mentioned above.
• the acid compound content is generally chosen so that the ratio between the number of moles in acid compound and the number of moles in carbon dioxide generator is between 1 and 2.
• the gelable compound can consist of one or more hydrophilic excipients causing the tablet to swell and trap the gas formed by the effervescence generator.
• one or more lipophilic excipients are combined with the hydrophilic excipient.
• the tablet in the liquid or on its surface, disintegrates under the action of effervescence. During this disintegration we observe the formation of viscous agglomerates which float and stick to the walls of the container and are suspended in the liquid. This process ends with the end of the effervescence and can, for example, last from 0.5 to 25 minutes depending on the type of liquid or drink.
• a pharmaceutical composition for oral administration, immediate release contains both an effervescence generator and a gelable compound
• another subsequent advantage of this composition lies in the improvement of the characteristics of absorption of the latter. In particular, a decrease in the interindividual variability of absorption can be observed compared to a conventional immediate release formulation. It is thus possible to obtain a regularization of the latency of appearance of the plasma concentrations, as well as a reduction in the variation of the plasma concentrations during the absorption phase.
• lipophilic excipients mention may be made of glycerol stearates, palmitostearates and behenates; hydrogenated vegetable oils and their derivatives; vegetable and animal waxes and their derivatives; hydrogenated castor oils and their derivatives and cetyl esters and alcohols.
• hydrophilic excipients mention may be made of cellulose derivatives, hydroxyethylcellulose, hydroxypropylcellulose (molecular weight from 50 to 1,250 kDa) hydroxypropylmethylcellulose (molecular weight from 10 to 1,500 kDa), carboxymethylcellulose and sodium carboxymethycellulose; vegetable gums and their derivatives; alginic acid derivatives; polyethylene glycols and their derivatives; starches and their derivatives; silicas and their derivatives; polymethacrylates and copolymers of acrylic and methacrylic acids.
• At least one of the constituents of the gelable compound can be chosen so as to be sparingly soluble in alcohol.
• the tablet, sparingly soluble in a liquid or an alcoholic drink of a degree greater than 45 slows down or even prevents the dissolution of the active principle and gives the liquid or the drink the appearance of a suspension of viscous insoluble particles.
• This dye can color the liquid or the particles or both simultaneously.
• the coloring of the particles is particularly advantageous in the case where the drink into which the tablet is introduced is dark (such as coffee, Coca Cola® or cocktails).
• dyes which can be used in the tablet according to the invention there may be mentioned indigotine, cochineal red, orange yellow S, allura red AC, iron oxides, Cucurmine, Riboflavin, Tartrazine, Quinoline yellow, Azorubine , Amarante, Carmins,
• Erythrosine Red 2G, Patented blue V, Bright blue FCF, Chlorophylls, Cupric complexes of chlorophylls, Green S, Caramels, Bright black BN, Vegetable carbon, Brown FK and HT, Carotenes, Annatto Extracts, Paprika Extracts, Lycopene, Lutein, Canthaxanthin, Beet red, Anthocyanins, Calcium carbonate, Titanium dioxide, Aluminum, Silver, Gold and Litholrubine BK or any other coloring suitable for consumption.
• additives can advantageously supplement the composition of the tablet.
• a disintegrating agent such as sodium carboxymethyl starch (molecular mass from 500 to 1000 kDa), such as the product marketed by Avebe under the brand Primojel ® or crosslinked polyvinylpyrrolidone or crospovidone, such as the product marketed by BASF under the brand Kolidon ® CL.
• a disintegrating agent such as sodium carboxymethyl starch (molecular mass from 500 to 1000 kDa), such as the product marketed by Avebe under the brand Primojel ® or crosslinked polyvinylpyrrolidone or crospovidone, such as the product marketed by BASF under the brand Kolidon ® CL.
• - lubricating agents such as magnesium stearate, stearic acid, glycerol monostearate, polyoxyethylene glycols having a molecular weight of 400 to 7,000,000, hydrogenated castor oil, behenate glycerol, mono-, bi- or trisubstituted glycerides, - flow agents, such as colloidal silica or any other silica, for example the product sold by Degussa under the brand Aerosil ⁇ , - binders such as starch, buffers , absorbents, diluents such as lactose and any other pharmaceutically acceptable additive.
• - lubricating agents such as magnesium stearate, stearic acid, glycerol monostearate, polyoxyethylene glycols having a molecular weight of 400 to 7,000,000, hydrogenated castor oil, behenate glycerol, mono-, bi- or trisubstituted glycerides
• - flow agents such as colloidal
• a tablet according to the present invention can be obtained by any conventional compression technology known to a person skilled in the art by mixing powders and / or granulation using, for example, rotary presses.
• Granulation can be carried out for example, according to a conventional technique, by mixing the various compounds to obtain a homogeneous powder, wetting with an alcoholic, aqueous or hydroalcoholic solution then drying until a percentage of residual moisture is obtained. predetermined, in a fluidized air bed, at temperatures between 25 and 80 ° C.
• the alcoholic solution can be based on polyvinylpyrrolidone (molecular mass from 28 to 1500 kDa) but also on hydropropylmethylcellulose or any other pharmaceutically acceptable binder.
• a tablet can take a cylindrical, lenticular, spheroidal, ovoid or other form, which allows for easy administration and swallowing.
• the mixture necessary for compression can also be obtained by dry granulation or direct mixing of the constituents.
• This film may have a base made of a polymeric material such as ethylcellulose, 1 hydroxypropylcellulose or hydroxypropylmethylcellulose and an opacifying agent such as titanium dioxide.
• This film can also be supplemented with any plasticizer and / or lubricant such as polyoxyethylene glycol 400 and colored with a dye er / or in the form of a lacquer such as indigotine lacquer.
• the amounts of active ingredient required are the same as those which are usually administered.
• the amount of zolpidem hemitartrate ranges from 3 to 10 mg.
• a particular embodiment of this tablet is, for example, a bilayer tablet provided with combined visual means constituted by flotation and the formation of insoluble particles:
• the first layer comprising an active principle exposed to the risk of misuse or a salt thereof, associated with at least one hydrophilic excipient as well as an effervescence generator,
• tracer layer comprising an effervescence generator and at least one gelable compound.
• the hydrophilic excipient of the active layer can be chosen from thickening and / or gelling agents and / or binders as described above.
• suitable hydrophilic excipients mention may be made of cellulose derivatives and in particular carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose and methylcellulose.
• sodium carboxymethylcellulose is preferred.
• the effervescent generator for the active layer the effervescent couple composed of calcium carbonate and anhydrous citric acid is preferred.
• the function of the tracer layer is to ensure flotation and the formation of insoluble particles making it possible to avoid any misuse of use at the expense of a third party.
• the tablet according to the present invention can not be dissolved in a glass of an alcoholic or non-alcoholic drink, without the person for whom the glass is intended to realize that the drink contains a foreign body.
• the bilayer tablet due to the presence in the tracer layer of an effervescence generator and of a gellable compound, floats on the surface of the drink into which it is introduced.
• the flotation time depends on the alcoholic degree of the drink and its temperature. It varies from 30 seconds to 15 minutes. In the case of highly alcoholic beverages (40 to 45%), the delay can reach several minutes (5 to 25 minutes).
• the same as those used for the active layer can be used as effervescence generators for the tracer layer.
• the effervescence generator of the tracer layer may be identical to or different from that of the active layer.
• the bilayer tablet may also advantageously contain a dye, examples of which have been given previously. This dye can be placed in the active layer or in the tracer layer or in the two layers at the same time.
• the two-layer tablets containing dye in the two layers are preferred in order to obtain both a coloration of the drink itself, but also a coloration of the insoluble particles. Thus, the coloration is visible on the surface of the drink during and after disintegration.
• the active layer can have a thickness which varies from 1 to 4 mm, and preferably from 1.5 to 2.5 mm.
• the tracer layer may have a thickness which varies from 1 to 4 mm, and preferably from 1.5 to 2.5 mm.
• the bilayer tablet according to the invention comprises from 0.1 to 40% by weight, preferably from 1 to 5% of active principle when it is zolpidem, from 0.5 to 50% by weight, preferably from 2 to 10% of hydrophilic excipient as gelable compound in the active layer, from 5 to 70% by weight, preferably from 25 to 50% of effervescence generator in the active layer and from 5 to 70% by weight , preferably from 15 to 35% of effervescence generator in the tracer layer and, as gelling compound, from 2 to 20% by weight, preferably from 4 to 10% of hydrophilic excipient in the tracer layer and 1 to 20% by weight, preferably from 1 to 5% of lipophilic excipient in the tracer layer, the percentages being expressed relative to the total weight of the composition.
• the tracer layer is obtained by direct mixing before compression, the active layer is obtained by alcoholic granulation.
• Glycerol behenate 2 5.60 5.60 2.15 Sodium bicarbonate 22.22 22.22 8.55 Calcium carbonate 5.00 5.00 1.92 Anhydrous citric acid 33.26 33.26 12.79
• Glycerol behenate 2 5.60 5.60 2.20
• Magnesium stearate 1.20 1.20 0.47 100.00 100.00 39.216
• active layer 1 (10 mg zolpidem hemitartrate) mg per% mass% compressed mass total layer Zolpidem hemitartrate 10.00 6.67 3.92 Carboxymethylcellulose
• Ethylcellulose 22N 1 1.22 24.40 0.48 Hydroxypropylcellulose 1.22 24.40 0.48 Titanium dioxide 2.44 48.80 0.96 Indigot lacquer 0.12 2.40 0.05
• the dissolution of zolpidem hemitartrate is greater than or equal to 80% in 15 minutes.
• the rotary vane apparatus of the European Pharmacopoeia is used with in each bowl 900 ml of 0.01 N hydrochloric acid degassed at a temperature of 37 ° C more or less 0.5 ° C (the tablet being ballasted to avoid its flotation).
• Example 1 flotation after introduction into a liquid
• One of the tablets of Example 1 is introduced into 10 to 20 cl of the following different drinks: red wine, white wine, hot coffee, orange juice and hot chocolate, strong alcohol. Floating, gassing is observed after 5 to 10 seconds in drinks at room temperature
• the tablet If the tablet is crushed and then introduced into an alcoholic drink or not, whatever its temperature, it causes an instant suspension and flotation of the fragments. There is formation of a gelling foam around the fragments and immediate and intense appearance of the coloring of the viscous particles which adhere to the walls of the container in the event of agitation.
• compositions of the invention therefore make it possible, by flotation and by the release of particles in drinks, to avoid ingestion by a person, without their knowledge.
• a measurement is carried out on a Rheostress RS 100 rheometer with a geometry of the plane cone type C 60/2 ° at 20 ° C, under a shear of 10 s -1 with a measurement duration. 300 s. A viscosity of between 1500 and 6000 mPa.s is obtained. This method is derived from the method for measuring the viscosity of the methocel K 100 M excipient.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Epidemiology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• General Chemical & Material Sciences (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Neurosurgery (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Anesthesiology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Zoology (AREA)
• Nutrition Science (AREA)
• Physiology (AREA)
• Medicinal Preparation (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Priority Applications (2)

Applications Claiming Priority (2)

Publications (1)

Family

ID=9534386

Family Applications (1)

Country Status (6)

Cited By (33)

Families Citing this family (7)

Citations (5)

• 1998
  • 1998-12-23 FR FR9816309A patent/FR2787715B1/fr not_active Expired - Lifetime
• 1999
  • 1999-12-14 EP EP99959478A patent/EP1140011A1/fr not_active Withdrawn
  • 1999-12-14 WO PCT/FR1999/003120 patent/WO2000038649A1/fr not_active Application Discontinuation
  • 1999-12-14 AU AU16639/00A patent/AU1663900A/en not_active Abandoned
  • 1999-12-22 AR ARP990106668A patent/AR021981A1/es unknown
  • 1999-12-22 CO CO99080034A patent/CO5150153A1/es unknown

Patent Citations (5)

Also Published As

Similar Documents

Legal Events