EP1076555A1 - Pectic preparations used as medicine carrier - Google Patents

Pectic preparations used as medicine carrier

Info

Publication number
EP1076555A1
EP1076555A1 EP99919330A EP99919330A EP1076555A1 EP 1076555 A1 EP1076555 A1 EP 1076555A1 EP 99919330 A EP99919330 A EP 99919330A EP 99919330 A EP99919330 A EP 99919330A EP 1076555 A1 EP1076555 A1 EP 1076555A1
Authority
EP
European Patent Office
Prior art keywords
pectin
pectic
preparation according
magnesium
pectic preparation
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Withdrawn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
EP99919330A
Other languages
German (de)
French (fr)
Inventor
René Tarral
Maurice Jacob
Jacky Mention
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.)
Gifrer Barbezat
Original Assignee
Gifrer Barbezat
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 Gifrer Barbezat filed Critical Gifrer Barbezat
Publication of EP1076555A1 publication Critical patent/EP1076555A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin

Definitions

  • the present invention relates to pectic preparations usable as a drug carrier, intended to be administered orally and capable of forming a gel in an acid medium, in the presence of calcium ions.
  • Patent FR-A-2733424 proposes pectic preparations capable of being easily dispersed in water and of constituting therein a stable suspension which, after ingestion, constitutes a gel in the stomach medium.
  • These compositions comprise at least one pectin, associated with calcium ions and with an effervescent couple which ensures both easy dispersion in water and hydration of pectin on the one hand, and regulation of the gelling process. on the other hand, whatever the hardness of the water used for the suspension.
  • this effervescent couple which is constituted by a mineral or organic acid or one of their salts, and a carbonate, has a buffering effect and an antacid activity. It requires a larger amount of acid to obtain the formation of a gel. It is therefore a "brake" for the gelling process in the stomach environment, that is to say at a pH below 6.
  • pectic preparations based on an effervescent couple require, before being ingested, a suspension in water, which is not always available.
  • the present invention therefore aims to remedy the aforementioned drawbacks, by providing pectic preparations usable as a drug carrier, in dry form, not forming a gel in the mouth and forming a gel in the stomach.
  • the subject of the invention is a pectic preparation, usable as a drug carrier, intended to be administered by the oral route and capable of forming a gel in an acid medium, comprising at least one pectin, having a degree of methoxylation greater than 15%, and ions calcium, characterized in that it contains an inhibitor of the gelling process at pH greater than 6, in an amount between 1 and 20 parts by weight per part of pectin and in that it is in dry form.
  • the gelling process inhibitor is a dare, or a mixture of dares, which can be chosen from the group consisting of mannitol, sorbitol, maltitol, xylitol, lactitol, maltol, l arabitol, inositol, erythrol, galactitol, and any product resulting from the reduction of the carbonyl function of a ose by chemical way.
  • the proportion of bone is between 1 and 20 parts by weight for one part of pectin.
  • the pectic preparation can contain other divalent cations useful for regulating the gelation process at pH ⁇ 6, that is to say in the stomach environment.
  • divalent cations are advantageously magnesium ions, which participate in the kinetics of availability of calcium.
  • Calcium and magnesium are provided in the form of hydroxides or insoluble or practically insoluble gels, such as calcium carbonate, calcium sulphate, tricalcium citrate, di- or tri-calcium phosphates, carbonate or hydroxycarbonate magnesium, magnesium trisilicate and magnesium stearate.
  • the proportions of calcium and magnesium are lower for each part to three parts for a part of pectin.
  • the pectin used comes from fruits of the apple and citrus groups. It is advantageously methoxylated with a degree of methoxylation greater than or equal to 15%. Preferably, it is a weakly methoxylated pectin (LM), its degree of methoxylation being less than 50%, produced by controlled demethylation of a highly esterified pectin (HM pectin), by acid or alkaline treatment.
  • the pectin can be non-amidated or amidated, with a degree of amidation advantageously less than 35%, and preferably less than or equal to 25%.
  • An amidated pectin is obtained by the aforementioned demethylation treatment, in an ammoniacal medium. By definition, the degree of amidation corresponds to the number of amide groups per 100 galacturonic acid units.
  • the preparations according to the invention can be used as a support for medicaments presented in dry forms such as granules and chewable tablets. Gelation does not occur in the mouth but only occurs in the stomach in the presence of the gastric acid environment.
  • preparations according to the invention can also be used as a carrier for medicaments presented in dry forms for extemporaneous oral suspension such as granules, dispersible tablets. They are then ingested after dispersion in drinking water and as before gelling occurs only in the stomach.
  • the pectic preparations When the pectic preparations must be presented in the form of granules, they are for example compacted by roller compaction and then the compacts are calibrated to the desired particle size. When they must be presented in tablet form, they are either granulated by dry process and then compressed, or compressed directly by direct compression.
  • the pectic preparations are added with the necessary compounds: filler excipients, flavors, sweeteners, disintegrants, lubricants, etc.
  • the pectic preparations according to the invention can be used in compositions for therapeutic purposes with prolonged local action or when it is desired to modify the conditions of release of the active principle (s): delay action for example.
  • active principle s: delay action for example.
  • Example_2 (comparative) In the tank of a blender by inversion, are introduced after having previously passed over a sieve with 1 mm mesh opening:
  • Example 1 The procedure of Example 1 is repeated, but the sucrose is replaced by mannitol.
  • Example 2 The procedure of Example 2 is repeated but with the replacement of the sucrose by sorbitol.
  • Example 2 The procedure of Example 2 is repeated but with replacement of the pectin of apple origin by a pectin of citrus origin and the sucrose by a 50/50 (m / m) sorbitol / mannitol mixture.
  • Example 7 chewable tablet Composition - non-amidated LM pectin 200 mg
  • the mixture is compressed on a rotary machine equipped with flat punches and 18 mm in diameter, with a unit weight of 2 g and an objective duration of 12 Kp.
  • a tablet is roughly ground and the coarse powder is introduced into 40 ml of water at pH 6.1 with gentle stirring. No gelation phenomenon was observed even after several minutes.
  • Example 8 dispersible tablet Composition
  • All the raw materials are passed through a sieve, except for the aroma. All the raw materials, with the exception of calcium carbonate and magnesium stearate, are introduced into an inverting mixer. Mix for 15 minutes. The calcium carbonate and the stearate are then added. Then mix again for 15 minutes.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Zoology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention concerns a pectic preparation useful as medicine carrier, to be orally administered and capable of forming a gel in an acid medium, comprising at least a pectin having a degree of methoxylation higher than 15 % and calcium ions, containing a gelling process inhibitor with pH higher than 6.

Description

Préparations pectiques utilisables comme support de médicament.Pectic preparations usable as drug carrier.
La présente invention concerne des préparations pectiques utilisables comme support de médicament, destinées à être administrées par voie orale et susceptibles de former un gel en milieu acide, en présence d'ions calcium.The present invention relates to pectic preparations usable as a drug carrier, intended to be administered orally and capable of forming a gel in an acid medium, in the presence of calcium ions.
Le brevet FR-A-2733424 propose des préparations pectiques susceptibles d'être aisément dispersées dans l'eau et d'y constituer une suspension stable, qui après ingestion, constitue un gel dans le milieu stomacal. Ces compositions comportent au moins une pectine, associée à des ions calcium et à un couple effervescent qui assure à la fois la dispersion aisée dans l'eau et l'hydratation de la pectine d'une part, et la régulation du processus de gélification d'autre part, quelle que soit la dureté de l'eau utilisée pour la mise en suspension.Patent FR-A-2733424 proposes pectic preparations capable of being easily dispersed in water and of constituting therein a stable suspension which, after ingestion, constitutes a gel in the stomach medium. These compositions comprise at least one pectin, associated with calcium ions and with an effervescent couple which ensures both easy dispersion in water and hydration of pectin on the one hand, and regulation of the gelling process. on the other hand, whatever the hardness of the water used for the suspension.
Cependant, ce couple effervescent, qui est constitué par un acide minéral ou organique ou un de leurs sels, et un carbonate, présente un effet tampon et une activité antacide. Il requiert une quantité plus importante d'acide pour obtenir la formation d'un gel. Il est donc un «frein» pour le processus de gélification dans le milieu stomacal, c'est-à-dire à un pH inférieur à 6.However, this effervescent couple, which is constituted by a mineral or organic acid or one of their salts, and a carbonate, has a buffering effect and an antacid activity. It requires a larger amount of acid to obtain the formation of a gel. It is therefore a "brake" for the gelling process in the stomach environment, that is to say at a pH below 6.
En outre, il complexe les cations divalents.In addition, it complexes divalent cations.
De plus, ces préparations pectiques à base d'un couple effervescent exigent, avant d'être ingérées, une mise en suspension dans l'eau, qui n'est pas toujours à disposition. La présente invention a donc pour but de remédier aux inconvénients précités, en proposant des préparations pectiques utilisables comme support de médicament, sous forme sèche, ne formant pas de gel dans la bouche et formant un gel dans l'estomac.In addition, these pectic preparations based on an effervescent couple require, before being ingested, a suspension in water, which is not always available. The present invention therefore aims to remedy the aforementioned drawbacks, by providing pectic preparations usable as a drug carrier, in dry form, not forming a gel in the mouth and forming a gel in the stomach.
A cet effet, l'invention a pour objet une préparation pectique, utilisable comme support de médicament, destinée à être administrée par voie orale et susceptible de former un gel en milieu acide, comportant au moins une pectine, présentant un degré de methoxylation supérieur à 15%, et des ions calcium, caractérisée en ce qu'elle renferme un inhibiteur du processus de gélification à pH supérieur à 6, en quantité comprise entre 1 et 20 parties en poids pour une partie de pectine et en ce qu'elle se présente sous forme sèche. De manière avantageuse, l'inhibiteur du processus de gélification est un ose, ou un mélange d'osés, qui peuvent être choisis dans le groupe constitué par le mannitol, le sorbitol, le maltitol, le xylitol, le lactitol, le maltol, l'arabitol, l'inositol, l'erythrol, le galactitol, et tout produit résultant de la réduction de la fonction carbonylique d'un ose par voie chimique. De préférence, la proportion d'osé est comprise entre 1 et 20 parties en poids pour une partie de pectine.To this end, the subject of the invention is a pectic preparation, usable as a drug carrier, intended to be administered by the oral route and capable of forming a gel in an acid medium, comprising at least one pectin, having a degree of methoxylation greater than 15%, and ions calcium, characterized in that it contains an inhibitor of the gelling process at pH greater than 6, in an amount between 1 and 20 parts by weight per part of pectin and in that it is in dry form. Advantageously, the gelling process inhibitor is a dare, or a mixture of dares, which can be chosen from the group consisting of mannitol, sorbitol, maltitol, xylitol, lactitol, maltol, l arabitol, inositol, erythrol, galactitol, and any product resulting from the reduction of the carbonyl function of a ose by chemical way. Preferably, the proportion of bone is between 1 and 20 parts by weight for one part of pectin.
Outre les ions calcium, la préparation pectique peut renfermer d'autres cations divalents utiles pour la régulation du processus de gélification à pH < 6, c'est-à-dire en milieu stomacal. Ces cations divalents sont avantageusement des ions magnésium, qui participent à la cinétique de disponibilité du calcium.In addition to the calcium ions, the pectic preparation can contain other divalent cations useful for regulating the gelation process at pH <6, that is to say in the stomach environment. These divalent cations are advantageously magnesium ions, which participate in the kinetics of availability of calcium.
Le calcium et le magnésium sont apportés sous forme dïiydroxydes ou de gels insolubles ou pratiquement insolubles, tels que le carbonate de calcium, le sulfate de calcium, le citrate tricalcique, les phosphates di- ou tri-calciques, le carbonate ou l'hydroxycarbonate de magnésium, le trisilicate de magnésium et le stéarate de magnésium.Calcium and magnesium are provided in the form of hydroxides or insoluble or practically insoluble gels, such as calcium carbonate, calcium sulphate, tricalcium citrate, di- or tri-calcium phosphates, carbonate or hydroxycarbonate magnesium, magnesium trisilicate and magnesium stearate.
De préférence les proportions de calcium et de magnésium sont inférieures pour chacune à trois parties pour une partie de pectine.Preferably the proportions of calcium and magnesium are lower for each part to three parts for a part of pectin.
La pectine utilisée est issue de fruits des groupes pommes et citrus. Elle est avantageusement méthoxylée avec un degré de methoxylation supérieur ou égal à 15%. De préférence, il s'agit d'une pectine faiblement méthoxylée (LM), son degré de methoxylation étant inférieur à 50%, fabriquée par déméthylation contrôlée d'une pectine fortement estérifiée (pectine HM), par traitement acide ou alcalin. La pectine peut être non amidée ou amidée, avec un degré d'amidation avantageusement inférieur à 35%, et de préférence inférieur ou égal à 25%. Une pectine amidée est obtenue par le traitement de déméthylation susmentionné, en milieu ammoniacal. Par définition, le degré d'amidation correspond au nombre de groupes amides pour 100 motifs acide galacturonique.The pectin used comes from fruits of the apple and citrus groups. It is advantageously methoxylated with a degree of methoxylation greater than or equal to 15%. Preferably, it is a weakly methoxylated pectin (LM), its degree of methoxylation being less than 50%, produced by controlled demethylation of a highly esterified pectin (HM pectin), by acid or alkaline treatment. The pectin can be non-amidated or amidated, with a degree of amidation advantageously less than 35%, and preferably less than or equal to 25%. An amidated pectin is obtained by the aforementioned demethylation treatment, in an ammoniacal medium. By definition, the degree of amidation corresponds to the number of amide groups per 100 galacturonic acid units.
Les préparations selon l'invention sont utilisables comme support de médicaments présentés sous formes sèches telles que granulés et comprimés à croquer. La gélification n'intervient pas dans la bouche mais n'intervient que dans l'estomac en présence du milieu acide gastrique.The preparations according to the invention can be used as a support for medicaments presented in dry forms such as granules and chewable tablets. Gelation does not occur in the mouth but only occurs in the stomach in the presence of the gastric acid environment.
Les préparations selon l'invention sont également utilisables comme support de médicaments présentés sous formes sèches pour suspension buvable extemporanées telles que granulés, comprimés dispersibles. Elles sont alors ingérées après dispersion dans l'eau potable et comme précédemment la gélification n'intervient que dans l'estomac.The preparations according to the invention can also be used as a carrier for medicaments presented in dry forms for extemporaneous oral suspension such as granules, dispersible tablets. They are then ingested after dispersion in drinking water and as before gelling occurs only in the stomach.
Lorsque les préparations pectiques doivent être présentées sous forme de granulé, elles sont par exemple compactées par compactage à rouleaux puis les compacts sont calibrés à la granulométrie souhaitée. Lorsqu'elles doivent être présentées sous forme de comprimé, elles sont soit granulées par voie sèche puis comprimées, soit comprimées directement par compression directe.When the pectic preparations must be presented in the form of granules, they are for example compacted by roller compaction and then the compacts are calibrated to the desired particle size. When they must be presented in tablet form, they are either granulated by dry process and then compressed, or compressed directly by direct compression.
Pour permettre la réalisation de la mise en forme pharmaceutique, les préparations pectiques sont additionnées des composés nécessaires: excipients de charge, arômes, édulcorants, désintégrants, lubrifiants, etc..To allow the pharmaceutical form to be carried out, the pectic preparations are added with the necessary compounds: filler excipients, flavors, sweeteners, disintegrants, lubricants, etc.
Les préparations pectiques selon l'invention peuvent être utilisées dans les compositions à visées thérapeutiques à action locale prolongée ou quand on désire modifier les conditions de libération du ou des principes actifs : action retard par exemple. Les exemples suivants permettent de mieux expliciter l'invention:The pectic preparations according to the invention can be used in compositions for therapeutic purposes with prolonged local action or when it is desired to modify the conditions of release of the active principle (s): delay action for example. The following examples allow the invention to be explained more clearly:
Exemple 1 (comparatif)Example 1 (comparative)
Dans la cuve d'un mélangeur par retournement, sont introduits après être préalablement passés sur tamis de 1 mm d'ouverture de maille: 200 parties en poids de pectine d'origine de pommes, amidée, avec un degré de methoxylation de 28% et un degré d'amidation de 18,3% (PH 320 NH)Into the tank of a blender by inversion, are introduced after having previously passed over a sieve with a mesh opening of 1 mm: 200 parts by weight of pectin of apple origin, amidated, with a degree of methoxylation of 28% and a degree of amidation of 18.3% (PH 320 NH)
1650 parties en poids de saccharose Après un mélange de 10 minutes sont ajoutées :1650 parts by weight of sucrose After mixing for 10 minutes are added:
50 parties en poids de carbonate de calcium préalablement passé sur tamis de 1 mm d'ouverture de maille, suivi d'un mélange à nouveau pendant 10 minutes. A 40 ml d'eau, sous légère agitation, est ajouté 1,9 g du mélange ci-dessus. On observe immédiatement la formation d'agglomérats et une gélification du milieu.50 parts by weight of calcium carbonate previously passed through a sieve with a mesh opening of 1 mm, followed by mixing again for 10 minutes. To 40 ml of water, with gentle stirring, is added 1.9 g of the above mixture. The formation of agglomerates and gelling of the medium are immediately observed.
Exemple_2 (comparatif) Dans la cuve d'un mélangeur par retournement, sont introduits après être préalablement passés sur tamis de 1 mm d'ouverture de maille :Example_2 (comparative) In the tank of a blender by inversion, are introduced after having previously passed over a sieve with 1 mm mesh opening:
200 parties en poids de pectine d'origine de pommes, non amidée, avec un degré de methoxylation de 32,5 % (Rouge NAND)200 parts by weight of pectin of apple origin, unamidated, with a degree of methoxylation of 32.5% (NAND Red)
1650 parties en poids de saccharose. Après un mélange de 10 minutes sont ajoutées:1650 parts by weight of sucrose. After mixing for 10 minutes are added:
50 parties en poids de carbonate de calcium préalablement passé sur tamis de 1 mm d'ouverture de maille.50 parts by weight of calcium carbonate previously passed through a sieve with 1 mm mesh opening.
Suivi d'un mélange de nouveau pendant 10 minutes.Follow with mixing again for 10 minutes.
A 40 ml d'eau, sous légère agitation, est ajouté 1,9 g du mélange ci-dessus. On observe immédiatement la formation d'agglomérats et une gélification du milieu.To 40 ml of water, with gentle stirring, is added 1.9 g of the above mixture. The formation of agglomerates and gelling of the medium are immediately observed.
Exemple 3Example 3
Le mode opératoire de l'exemple 1 est répété, mais le saccharose est remplacé par du mannitol.The procedure of Example 1 is repeated, but the sucrose is replaced by mannitol.
A 40 ml d'eau, sous légère agitation, on ajoute 1,9 g du mélange. Il n'est pas observé de phénomène de gélification même après plusieurs minutes.To 40 ml of water, with slight stirring, 1.9 g of the mixture are added. No gelation phenomenon was observed even after several minutes.
La suspension est alors additionnée de 5 ml d'acide chlorhydrique 0,1 N. Il y a immédiatement gélification du milieu. Exemple 45 ml of 0.1N hydrochloric acid are then added to the suspension. The medium is immediately gelled. Example 4
Le mode opératoire de l'exemple 2 est répété mais avec remplacement du saccharose par du sorbitol.The procedure of Example 2 is repeated but with the replacement of the sucrose by sorbitol.
A 40 ml d'eau préalablement ajustée à pH 6,2, on ajoute 1,9 g du mélange sous légère agitation. IL n'est pas observé de phénomène de gélification même après plusieurs minutes.1.9 g of the mixture are added to 40 ml of water previously adjusted to pH 6.2, with gentle stirring. There is no gelation phenomenon observed even after several minutes.
La suspension est alors additionnée de 5 ml d'acide chlorhydrique 0, 1 N. Il y a immédiatement gélification du milieu.5 ml of 0.1N hydrochloric acid are then added to the suspension. The medium is immediately gelled.
Exemple 5Example 5
Le mode opératoire de l'exemple 2 est répété mais avec remplacement de la pectine d'origine de pomme par une pectine d'origine citrus et le saccharose par un mélange 50/50 (m/m) sorbitol/mannitol.The procedure of Example 2 is repeated but with replacement of the pectin of apple origin by a pectin of citrus origin and the sucrose by a 50/50 (m / m) sorbitol / mannitol mixture.
A 40 ml d'eau préalablement ajustée à pH 6,3 on ajoute 1,9 g du mélange sous légère agitation. Il n'est pas observé de phénomène de gélification même après plusieurs minutes.To 40 ml of water previously adjusted to pH 6.3, 1.9 g of the mixture are added with gentle stirring. No gelation phenomenon was observed even after several minutes.
La suspension est alors additionnée de 5 ml d'acide chlorhydrique 0, 1 N. Il y a immédiatement gélification du milieu.5 ml of 0.1N hydrochloric acid are then added to the suspension. The medium is immediately gelled.
Exemple 6Example 6
Dans la cuve d'un mélangeur par retournement, on introduit après les avoir préalablement passés sur tamis de 1 mm d'ouverture de maille:In the tank of a mixer by inversion, the following are introduced after having previously passed through a sieve with a mesh opening of 1 mm:
200 parties en poids de pectine d'origine citrus avec un degré de methoxylation de 25 % et un degré d'amidation de 23% (Rouge NHND) 600 parties de sorbitol200 parts by weight of pectin of citrus origin with a degree of methoxylation of 25% and a degree of amidation of 23% (Red NHND) 600 parts of sorbitol
1000 parties de mannitol1000 parts of mannitol
On mélange pendant 10 minutes.Mix for 10 minutes.
Puis on ajoute au mélange:Then add to the mixture:
70 parties de carbonate de calcium 30 parties de trisilicate de magnésium On mélange de nouveau pendant 10 minutes.70 parts of calcium carbonate 30 parts of magnesium trisilicate Mix again for 10 minutes.
A 40 ml d'eau, sous légère agitation, on ajoute 1,9 g du mélange ci-dessus. Il n'est pas observé de phénomène de gélification même après plusieurs minutes. La suspension est alors additionnée de 5 ml d'acide chlorhydrique 0,1 N. Il y a immédiatement gélification du milieu.To 40 ml of water, with slight stirring, 1.9 g of the above mixture are added. No gelation phenomenon was observed even after several minutes. 5 ml of 0.1N hydrochloric acid are then added to the suspension. The medium is immediately gelled.
Exemple 7: comprimé à croquer Composition - pectine LM non amidée 200 mgExample 7: chewable tablet Composition - non-amidated LM pectin 200 mg
- carbonate de calcium 700 mg- calcium carbonate 700 mg
- potassium acesulfame 5 mg- potassium acesulfame 5 mg
- arôme 12 mg- flavor 12 mg
- stéarate de magnésium 15 mg - mannitol 1068 mg- magnesium stearate 15 mg - mannitol 1068 mg
TOTAL 2000 mgTOTAL 2000 mg
On passe l'ensemble des matières premières sur tamis de 1 mm à l'exception de l'arôme.All the raw materials are passed through a 1 mm sieve, except for the aroma.
Dans un mélangeur par retournement, on introduit la totalité des constituants à l'exception du carbonate de calcium et du stéarate de magnésium. On mélange pendant 15 minutes. On ajoute alors le carbonate de calcium et le stéarate puis on mélange pendant 15 minutes.In all of the constituents, with the exception of calcium carbonate and magnesium stearate, are introduced into an inverting mixer. Mix for 15 minutes. The calcium carbonate and the stearate are then added and then mixed for 15 minutes.
Le mélange est comprimé sur machine rotative équipée de poinçons plat et de 18 mm de diamètre, au poids unitaire de 2 g et à une durée objective de 12 Kp.The mixture is compressed on a rotary machine equipped with flat punches and 18 mm in diameter, with a unit weight of 2 g and an objective duration of 12 Kp.
On broie grossièrement un comprimé et on introduit la poudre grossière dans 40 ml d'eau à pH 6,1 sous légère agitation. Il n'est pas observé de phénomène de gélification même après plusieurs minutes.A tablet is roughly ground and the coarse powder is introduced into 40 ml of water at pH 6.1 with gentle stirring. No gelation phenomenon was observed even after several minutes.
Lorsqu'on ajoute 5 ml d'acide chlorhydrique 0,1 N à la suspension, il se forme immédiatement un gel qui s'épaissit dans le temps. Exemple 8: comprimé dispersible CompositionWhen 5 ml of 0.1 N hydrochloric acid is added to the suspension, a gel which thickens over time is immediately formed. Example 8: dispersible tablet Composition
- pectine LM non amidée 200 mg - carbonate de calcium 600 mg- non-amidated LM pectin 200 mg - calcium carbonate 600 mg
- acesulfame potassium 8 mg- acesulfame potassium 8 mg
- arôme 15 mg- flavor 15 mg
- crospovidone 100 mg- crospovidone 100 mg
- stéarate de magnésium 15 mg - mannitol 1552 mg- magnesium stearate 15 mg - mannitol 1552 mg
Total 2500 mgTotal 2500 mg
On passe l'ensemble des matières premières sur tamis, à l'exception de l'arôme. Dans un mélangeur par retournement on introduit la totalité des matières premières à l'exception du carbonate de calcium et du stéarate de magnésium. On mélange pendant 15 minutes. On ajoute alors le carbonate de calcium et le stéarate. Puis on mélange de nouveau pendant 15 minutes.All the raw materials are passed through a sieve, except for the aroma. All the raw materials, with the exception of calcium carbonate and magnesium stearate, are introduced into an inverting mixer. Mix for 15 minutes. The calcium carbonate and the stearate are then added. Then mix again for 15 minutes.
On comprime sur machine équipée de poinçons plats de diamètre 20 mm, au poids unitaire de 2500 mg et à une dureté objective de 8 à 12 Kp.It is compressed on a machine equipped with flat punches with a diameter of 20 mm, with a unit weight of 2500 mg and an objective hardness of 8 to 12 Kp.
Lorsqu'on introduit un comprimé dans 40 ml d'eau à pH 6, 1, le comprimé se disperse et il n'est pas observé de formation de gel même après plusieurs minutes. Si l'on ajoute 5 ml d'acide chlorhydrique 0,1 N, il y a aussitôt gélification du milieu. When a tablet is introduced into 40 ml of water at pH 6.1, the tablet disperses and no gel formation is observed even after several minutes. If 5 ml of 0.1 N hydrochloric acid is added, the medium immediately gels.

Claims

REVENDICATIONS
1. Préparation pectique, utilisable comme support de médicament, destinée à être administrée par voie orale et susceptible de former un gel en milieu acide, comportant au moins une pectine présentant un degré de methoxylation supérieur à 15 % et des ions calcium, caractérisée en ce qu'elle renferme un inhibiteur du processus de gélification à pH supérieur à 6 en quantité comprise entre 1 et 20 parties en poids pour une partie de pectine et en ce qu'elle se présente sous forme sèche. 1. Pectic preparation, usable as a medicament carrier, intended to be administered orally and capable of forming a gel in an acid medium, comprising at least one pectin having a degree of methoxylation greater than 15% and calcium ions, characterized in that that it contains an inhibitor of the gelling process at a pH greater than 6 in an amount between 1 and 20 parts by weight per part of pectin and in that it is in dry form.
2. Préparation pectique selon la revendication 1, caractérisée en ce que l'inhibiteur du processus de gélification est un ose, ou un mélange d'osés.2. Pectic preparation according to claim 1, characterized in that the inhibitor of the gelling process is a dare, or a mixture of daring.
3. Préparation pectique selon la revendication 2, caractérisée en ce que l'ose, ou les oses, sont choisis dans le groupe constitué par : le mannitol, le sorbitol, le maltitol, le xylitol, le lactitol, le maltol, l'arabitol, l'inositol, l'erythrol, le galactitol.3. Pectic preparation according to claim 2, characterized in that the ose, or the oses, are chosen from the group consisting of: mannitol, sorbitol, maltitol, xylitol, lactitol, maltol, arabitol , inositol, erythrol, galactitol.
4. Préparation pectique selon l'une des revendications précédentes, caractérisée en ce qu'elle renferme également, pour la régulation du processus de gélification à pH < 6, des cations divalents autres que les ions calcium. 4. Pectic preparation according to one of the preceding claims, characterized in that it also contains, for the regulation of the gelling process at pH <6, divalent cations other than calcium ions.
5. Préparation pectique selon la revendication 4, caractérisée en ce que les cations divalents sont des ions magnésium.5. Pectic preparation according to claim 4, characterized in that the divalent cations are magnesium ions.
6. Préparation pectique selon l'une des revendications 1 à 5 caractérisée en ce que la pectine est une pectine amidée.6. Pectic preparation according to one of claims 1 to 5 characterized in that the pectin is an amidated pectin.
7. Préparation pectique selon l'une des revendications 1 à 5 caractérisée en ce que la pectine est une pectine non amidée.7. Pectic preparation according to one of claims 1 to 5 characterized in that the pectin is a non-amidated pectin.
8. Préparation pectique selon l'une quelconque des revendications précédentes, caractérisée en ce que les ions calcium sont apportés sous forme de carbonate de calcium.8. Pectic preparation according to any one of the preceding claims, characterized in that the calcium ions are provided in the form of calcium carbonate.
9. Préparation pectique selon l'une des revendications 4 à 8, caractérisée en ce que les ions magnésium sont apportés sous forme driydroxydes ou de sels insolubles. 9. Pectic preparation according to one of claims 4 to 8, characterized in that the magnesium ions are provided in the form of hydroxides or insoluble salts.
10. Préparation pectique selon la revendication 9 caractérisée en ce que les sels de magnésium sont le trisilicate de magnésium, le stéarate de magnésium, le carbonate ou hydrocarbonate de magnésium.10. Pectic preparation according to claim 9 characterized in that the magnesium salts are magnesium trisilicate, magnesium stearate, carbonate or magnesium hydrocarbonate.
11. Composition pharmaceutique caractérisée en ce qu'elle comprend une préparation pectique sous forme sèche selon l'une quelconque des revendications précédentes et un principe actif comme médicament. 11. Pharmaceutical composition characterized in that it comprises a pectic preparation in dry form according to any one of the preceding claims and an active principle as a medicament.
EP99919330A 1998-05-15 1999-05-14 Pectic preparations used as medicine carrier Withdrawn EP1076555A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9806143 1998-05-15
FR9806143A FR2778566B1 (en) 1998-05-15 1998-05-15 PECTIC PREPARATIONS FOR USE AS MEDICINAL MEDIA
PCT/FR1999/001157 WO1999059542A1 (en) 1998-05-15 1999-05-14 Pectic preparations used as medicine carrier

Publications (1)

Publication Number Publication Date
EP1076555A1 true EP1076555A1 (en) 2001-02-21

Family

ID=9526390

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99919330A Withdrawn EP1076555A1 (en) 1998-05-15 1999-05-14 Pectic preparations used as medicine carrier

Country Status (3)

Country Link
EP (1) EP1076555A1 (en)
FR (1) FR2778566B1 (en)
WO (1) WO1999059542A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7494669B2 (en) * 2001-02-28 2009-02-24 Carrington Laboratories, Inc. Delivery of physiological agents with in-situ gels comprising anionic polysaccharides
US6989166B2 (en) * 2001-12-20 2006-01-24 N.V. Nutricia Soft drink replacer
RU2012147899A (en) 2010-05-24 2014-06-27 Америлаб Текнолоджиз, Инк. Effervescent composition for the formation of a gelatinized composition, tablet for the formation of a gelatinized composition and a method of making a gelatinized composition
JP7162618B2 (en) * 2017-05-12 2022-10-28 コーニング インコーポレイテッド Crosslinked shear-thinning fluids with tunable rheology for 3D bioprinting and drug delivery

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK179687D0 (en) * 1987-04-08 1987-04-08 Farma Food As PREPARATION
US5358702A (en) * 1990-04-10 1994-10-25 Unger Evan C Methoxylated gel particle contrast media for improved diagnostic imaging
FR2733420B1 (en) * 1995-04-28 1997-06-27 Sep Tarral PECTIC PREPARATIONS FOR USE AS MEDICINAL MEDIA

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9959542A1 *

Also Published As

Publication number Publication date
FR2778566A1 (en) 1999-11-19
FR2778566B1 (en) 2001-07-20
WO1999059542A1 (en) 1999-11-25

Similar Documents

Publication Publication Date Title
CA2072513C (en) Lozenge or chewable tablet
JP2907299B2 (en) Pharmaceutical preparations that bind stomach acid
RU2403033C2 (en) Solubilised ibuprofen
CA2061520C (en) Delivery system for enhanced onset and increased potency
TWI317740B (en) Cellulose powder
EA004951B1 (en) Process for preparing oral calcium compositions
KR20010024184A (en) Pharmaceutical preparation comprising clodronate as active ingredient and silicified microcrystalline cellulose as excipient
JP2002524492A5 (en)
CZ294084B6 (en) Free flowing granular composition, process for its preparation and antifoam simethicone oral solid dosage form
MXPA06002257A (en) Pharmaceutical formulation comprising lanthanum compounds.
DE60300862T2 (en) IMPROVEMENTS ON OR RELATED TO PHARMACEUTICAL COMPOSITIONS
RU2161033C2 (en) Combined osmotic and volume-forming purgative agents
US5219889A (en) Dietary supplementation with potassium magnesium citrate
US6447807B1 (en) Potassium (-)-hydroxycitric acid methods for pharmaceutical preparations for stable and controlled delivery
JPS58501590A (en) Bismuth-containing composition and method for producing the composition
FR2563108A1 (en) ANTIACID PHARMACEUTICAL COMPOSITION AND AQUEOUS SUSPENSION CONTAINING THE SAME
US4985593A (en) Magnesium potassium citrate
US5919491A (en) Method and composition for increasing calcium uptake
WO1999059542A1 (en) Pectic preparations used as medicine carrier
US4895980A (en) Method of manufacturing magnesium potassium citrate
US7189416B2 (en) Method for stable and controlled delivery of (-)-hydroxycitric acid
WO1992022305A1 (en) Therapeutic composition for sustained release of magnesium
EP0715520B1 (en) Use of a suspension based on sucralphate gel as antacid
CN1193906A (en) Therapeutic effervescent compositions
EP3094334B1 (en) Pharmaceutical composition comprising a combination of a bisphosphonate and cholecalciferol and method for the preparation thereof

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20001027

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE ES FR GB GR IT LI LU NL PT SE

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20050208