(19)
(11)EP 2 814 467 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
11.03.2020 Bulletin 2020/11

(21)Application number: 13749952.1

(22)Date of filing:  18.02.2013
(51)International Patent Classification (IPC): 
A61K 9/24(2006.01)
A61K 47/36(2006.01)
A61K 9/20(2006.01)
A61K 47/02(2006.01)
(86)International application number:
PCT/US2013/026609
(87)International publication number:
WO 2013/123487 (22.08.2013 Gazette  2013/34)

(54)

ALKALIZED ACACIA GUM ADHESIVE FOR ORAL ADHERING DISCS

ALKALISIERTER AKAZIENGUMMIKLEBSTOFF ZUM KLEBEN VON PLATTEN IM MUNDRAUM

ADHÉSIF À BASE DE GOMME ARABIQUE ALCALINISÉE POUR DISQUES ADHÉSIFS ORAUX


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
Designated Extension States:
BA ME

(30)Priority: 19.02.2012 US 201261600659 P

(43)Date of publication of application:
24.12.2014 Bulletin 2014/52

(60)Divisional application:
20153705.7

(73)Proprietor: Quest Products, LLC
Pleasant Prairie, WI 53158 (US)

(72)Inventor:
  • HALEY, Jeffrey T.
    Mercer Island Washington 98040 (US)

(74)Representative: Fleuchaus, Andrea et al
Fleuchaus & Gallo Partnerschaft mbB Patentanwälte Steinerstraße 15/Haus A
81369 München
81369 München (DE)


(56)References cited: : 
EP-A1- 1 980 245
WO-A1-2007/139661
WO-A2-2009/043588
US-A1- 2007 081 949
WO-A1-2007/120768
WO-A2-2009/036084
RU-C2- 2 234 337
US-A1- 2007 274 927
  
      
    Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


    Description

    BACKGROUND



    [0001] Oral adhering discs, also called adhering troches, are known for time release of ingredients into saliva in the mouth or into the mucosa to which
    the disc is adhered or into mucosa that the disc touches while the disc is adhered to teeth or gums. Some oral adhering discs have two layers, a thin adhesive layer and a thicker, slowly dissolving ingredient release layer. Many synthetic hydrophilic compounds are known for use as the adhesive layer, such as poly-acrylic acid, carbomer, carbopol, and povidone. An effective natural compound, in sufficient concentration, is acacia gum, also known as gum arabic. WO 2009/036084 for example describes an adhering bi layer troche with an adhesive layer made of 80-100% and explicitly 99% acacia gum. As it dissolves in saliva, acacia gum adhesive is acidic, producing a local pH below 5.5, which is more acidic than desirable for contact with teeth.

    [0002] Of course, the adhering objects need not be disc shaped. They may be squarish or oval or oblong or any other shape that is roughly flat at least on one side. A generic term that includes all such shapes is "adhering troche" (which a term for an object held in the mouth to achieve an effect).

    SUMMARY OF THE INVENTION



    [0003] The present invention provides a natural muco-adhesive composition that is effective for adhering troches and is less acidic than pure acacia gum made by mixing an alkalizer (base) with the acacia gum.

    [0004] In one aspect, the invention is an adhering troche having two sides that, when held in a human mouth, adheres and remains in the mouth as a single item that does not smear or break apart, made by a process comprising, (a) forming a first layer, roughly disc-shaped and having a roughly flat side at least 5 mm in two dimensions, comprising an ingredient to be released into saliva and/or mucosa; (b) forming a second, adhesive layer, roughly disc- shaped and having a roughly flat side at least 5 mm in two dimensions, comprising at least 80% acacia gum mixed with a sufficient quantity of alkalizer that the pH of the mixture is 5.5 or higher when dissolved in 10 parts water; and (c) adhering the layers to each other, side to side, such that one entire side of the resulting troche is adhesive and the other entire side of the resulting troche is not adhesive.

    [0005] The particles of the alkalizer may be adhered to particles of the acacia gum by a wet granulation process and the resulting combined particles may then be pressed into a bi-layer troche with a bi-layer tablet press.

    [0006] The particles of the alkalizer may be wet mixed with particles of the acacia gum and the resulting mixture then dried into granules and the granules then pressed into a bi-layer troche with a bi-layer tablet press.
    The particles of the alkalizer may be wet mixed with particles of the acacia gum and the resulting mixture then spread into a layer on a sheet and the sheet then cut into a bi-layer troche.
    The particles of the alkalizer may be mixed with particles of the acacia gum and the resulting mixture then pressure extruded to make a bi-layer sheet which may be cut into troches. These adhering troches may be made by hot pressing the sheet with dies that hot-squish the sheet to separate it into individual troches and then cooling.
    The adhesive layer adheres to a roof of a mouth of a human strongly enough to hold triple the weight of the troche against force of gravity and strongly enough to hold the weight of the troche plus an additional 680 milligrams against force of gravity.
    The preferred alkalizer is calcium carbonate.
    In another aspect, the invention is an adhering troche having two sides that, when held in a human mouth, adheres and remains in the mouth as a single item that does not smear or break apart, comprising (a) a first layer, roughly disc-shaped and having a roughly flat side at least 5 mm in two dimensions, comprising an ingredient to be released into saliva or mucosa; (b) a second, adhesive layer, roughly disc-shaped and having a roughly flat side at least 5 mm in two dimensions, comprising at least 80% acacia gum mixed with a sufficient quantity of alkalizer that the pH of the mixture is 5.5 or higher when dissolved in 10 parts water; and (c) the layers being adhered to each other, side to side, such that one entire side of the resulting troche is adhesive and the other entire side of the resulting troche is not adhesive.
    In another aspect, the invention is an adhering troche, at least 5 mm in two dimensions, that, when held in a human mouth, adheres and remains in the mouth as a single item that does not smear or break apart, comprising, (a) a first layer comprising an ingredient to be released into saliva; and (b) a second, adhesive layer comprising at least 80% acacia gum mixed with a sufficient quantity of alkalizer that the pH of the mixture 5.5 or higher dissolved in 10 parts water.

    Description of the Drawing



    [0007] Figure 1 presents a table of experimental embodiments of the invention made with mixtures of acacia gum with calcium carbonate.

    DETAILED DESCRIPTION OF THE INVENTION



    [0008] In preferred embodiments, the acacia gum is pressed from a dry powder into one layer of a bi-layer disc with a bi-layer tablet press as taught by US patent application # 11/800381 filed May 4, 2007 by the same inventor. The alkalizer (base) may be mixed as a dry powder with the acacia gum powder, or it may be granulated with the acacia gum powder in a wet-granulation process or a dry granulation process.
    In an alternative embodiment, the acacia gum may be mixed with a liquid such as water or alcohol to form a thick paste which is then spread onto a sheet, such as a sheet of a composition including an ingredient to be delivered. The sheet may be dried and then cut into discs or first cut into discs and then dried. The alkalizer is mixed into the paste before spreading on the sheet.
    In another alternative embodiment, the acacia gum may be mixed with the alkalizer and then pressure extruded to form a sheet from which discs are cut.
    The alkalizer (base) is added in the least amount that achieves the desired neutralization, to keep the acacia gum as concentrated as possible to maintain maximum adhesive effectiveness.
    To be an effective adhesive layer for a thin oral adhering disc weighing less than 340 milligrams, the adhesive layer should adhere to a roof of a mouth of a human strongly enough to hold triple the weight of the disc against force of gravity.
    To be an effective adhesive layer for a thick oral adhering disc weighing more than 340 milligrams, the adhesive layer should adhere to a roof of a mouth of a human strongly enough to hold the weight of the disc plus an additional 680 milligrams against force of gravity.
    In the case of acacia gum, for adequate adhesive strength, the acacia gum should be at least 80%, allowing up to 20% alkalizer or other additives.
    Any known alkalizer that allows the finished product to remain adequately shelf stable may be used.
    The alkalizer may be mixed with wet acacia gum, neutralizing the acacia gum before it is granulated, dried, and tablet pressed or spread as a paste. In this method, a strong alkalizer, such as KOH (potassium hydroxide) or sodium hydroxide, may be used and titrated to a pH between 5.5 and 8.0, preferably 6.0 - 7.0.
    For ease of manufacturing finished discs with a bi-layer tablet press, it is preferred to obtain the acacia gum as a powder, then mix in a powdered alkalizer, and then use the mixture directly in a tablet press. Any alkalizer that can be obtained as a powder and will remain shelf stable when mixed with powdered acacia gum can be used. Examples include calcium carbonate, magnesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium carbonate, magnesium hydroxide, aluminum hydroxide, and C7H5BiO4.

    [0009] Effective ratios of calcium carbonate to acacia gum range down to 1:50. A preferred formulation uses fine powder calcium carbonate in a ratio with acacia gum calcium within the range 1 : 15 to 1 : 50. The presently most preferred ratio is 1 to 40. Tests show that this mixture keeps the pH above 5.5 as the mixture dissolves in distilled water. Measured pH's range from 6.0 to 6.4. If the amount of calcium carbonate is increased, the pH can be as high as 7.0 but this is not optimal as the adhesiveness of the acacia gum is somewhat reduced.

    [0010] The powders may be pressed into a disc shaped tablet. Such a tablet is preferably 9-16 mm in diameter and 70-800 milligrams in weight. The upper punch should be shaped for good contact with a surface in the mouth, usually essentially flat, sometimes with a bump in the center to create a dimple in the disc surface, sometimes cupped to give a domed surface such as for adhesion to the roof of the mouth. The lower punch may be cupped to provide a domed outer surface on a thick disc, or it may be nearly flat for a thin disc.

    EXAMPLES



    [0011] The following examples are presented by way of illustration and not by way of limitation on the scope of the invention. To determine appropriate ratios, dry acacia gum was mixed with 10 parts water and the resulting pH was measured at 4.4. The pH was also measured for the following mixtures:
    EXAMPLE 1
    WaterAcacia gumCaCO3Ratio AG/CaCO3pH
    40 4.4 0.6 7.3 :1 > 7.0
    108.2 4.8 0.6 8 : 1 > 7.0
    108.2 5.6 0.6 9.3 : 1 6.7
    108.2 8.4 0.6 14 : 1 6.5
    6.6 3.3 .22 15:1 6.45
    7.0 3.0 .16 19 : 1 6.4
    12.3 4.0 .20 20 : 1 6.35
    9.46 5.5 .27 20 : 1 6.25
    7.0 3.0 .12 25 : 1 6.1
    15.8 7.32 .28 26 : 1 6.2
    15.8 7.32 .22 33 : 1 6 . 1
    13.5 6.59 .18 37 : 1 6.3
    13.5 6.59 .16 41:1 6.1
    EXAMPLE 2
    WaterAcacia gumNaHCO3Ratio AG/alkalipH
    6.3 1.8 .28 6.4 : 1 8.04
    EXAMPLE 3
    WaterAcacia gumK2HPO4Ratio AG/alkalipH
    6.3 1.8 .28 6.4 : 1 8.04
    4.2 3.2 .16 20 : 1 5.8



    Claims

    1. An adhering troche having two sides that, when held in a human mouth, adheres and remains in the mouth as a single item that does not smear or break apart, made by a process comprising:

    (a) forming a first layer, roughly disc-shaped and having a roughly flat side at least 5 mm in two dimensions, comprising an ingredient to be released into saliva;

    (b) forming a second, adhesive layer, roughly disc-shaped and having a roughly flat side at least 5 mm in two dimensions, comprising at least 80% acacia gum mixed with up to 20% alkalizer selected to be calcium carbonate and yielding a pH of the mixture of 5.5 or higher when dissolved in 10 parts water; and

    (c) adhering the layers to each other, side to side, such that a first entire side of the resulting troche is adhesive and a second entire side of the resulting troche is not adhesive.


     
    2. The adhering troche of claim 1 wherein particles of calcium carbonate were adhered to particles of the acacia gum by a wet granulation process and the resulting combined particles were then pressed into a bi-layer troche with a bi-layer tablet press.
     
    3. The adhering troche of claim 1 wherein particles of calcium carbonate were dry mixed with particles of the acacia gum and the resulting mixture was then pressed into a bi-layer troche with a bi-layer tablet press.
     
    4. The adhering troche of claim 1 wherein particles of calcium carbonate were wet mixed with particles of the acacia gum and the resulting mixture was then dried into granules and the granules were then pressed into a bi-layer troche with a bi-layer tablet press.
     
    5. The adhering troche of claim 1 wherein particles of calcium carbonate were wet mixed with particles of the acacia gum and the resulting mixture was then spread into a layer on a sheet and the sheet was then cut into a bi-layer troche.
     
    6. The adhering troche of claim 1 wherein particles of calcium carbonate were mixed with particles of the acacia gum and the resulting mixture was then pressure extruded to make a bi-layer sheet which was cut into troches.
     
    7. The adhering troche of claim 6 made by hot pressing the sheet with dies that hot-squish the sheet to separate it into individual troches and then cooling.
     
    8. The adhering troche of claim 1 wherein the adhesive layer adheres to a roof of a mouth of a human strongly enough to hold triple the weight of the troche against force of gravity.
     
    9. The adhering troche of claim 1 wherein the adhesive layer adheres to a roof of a mouth of a human strongly enough to hold the weight of the troche plus an additional 680 milligrams against force of gravity.
     
    10. The adhering troche obtained according to claim 1 and having two sides comprising:

    (a) a first layer, roughly disc-shaped and having a roughly flat side at least 5 mm in two dimensions, comprising an ingredient to be released into saliva;

    (b) a second, adhesive layer, roughly disc-shaped and having a roughly flat side at least 5 mm in two dimensions, comprising at least 80% acacia gum mixed with up to 20% alkalizer selected to be calcium carbonate and yielding a pH of the mixture of 5.5 or higher when dissolved in 10 parts water; and

    (c) the layers adhered to each other, side to side, such that one entire side of the resulting troche is adhesive and the other entire side of the resulting troche is not adhesive.


     
    11. The adhering troche according to claim 10 having at least 5 mm in two dimensions, that, when held in a human mouth, adheres and remains in the mouth as a single item that does not smear or break apart, comprising:

    (a) a first layer comprising an ingredient to be released into saliva; and

    (b) a second, adhesive layer comprising at least 80% acacia gum mixed with and up to 20% alkalizer selected to be calcium carbonate and yielding a pH of the mixture of 5.5 or higher when dissolved in 10 parts water.


     


    Ansprüche

    1. Eine anhaftende Pastille mit zwei Seiten, die, wenn sie in einem menschlichen Mund gehalten wird, als ein einziger Gegenstand, der nicht verschmiert oder auseinanderbricht, im Mund klebt und dort verbleibt, hergestellt durch ein Verfahren, das Folgendes umfasst:

    (a) Bilden einer ersten Schicht, die nahezu scheibenförmig ist und eine nahezu flache Seite von mindestens 5 mm in zwei Dimensionen hat, mit einem Inhaltsstoff, der in den Speichel abgegeben werden soll;

    (b) Bilden einer zweiten, klebenden Schicht, die nahezu scheibenförmig ist und eine nahezu flache Seite von mindestens 5 mm in zwei Dimensionen aufweist, die mindestens 80% Akaziengummi gemischt mit bis zu 20% Alkalisierungsmittel, das als Kalziumkarbonat ausgewählt ist, enthält und einen pH-Wert der Mischung von 5,5 oder höher ergibt, wenn sie in 10 Teilen Wasser gelöst wird; und

    (c) die Schichten Seite an Seite so aneinander zu kleben, dass eine erste ganze Seite der resultierenden Pastille klebend ist und eine zweite ganze Seite der resultierenden Pastille nicht klebend ist.


     
    2. Anhaftende Pastille nach Anspruch 1, bei der Partikel aus Kalziumkarbonat durch ein Nassgranulationsverfahren an Partikel des Akaziengummis geklebt wurden und die resultierenden kombinierten Partikel dann mit einer Zweischicht-Tablettenpresse zu einer Zweischicht-Pastille gepresst wurden.
     
    3. Anhaftende Pastille nach Anspruch 1, wobei Partikel aus Kalziumkarbonat mit Partikeln des Akaziengummis trocken gemischt wurden und die resultierende Mischung dann mit einer Zweischicht-Tablettenpresse zu einer Zweischicht-Pastille gepresst wurde.
     
    4. Anhaftende Pastille nach Anspruch 1, bei der Partikel aus Kalziumkarbonat mit Partikeln des Akaziengummis nass gemischt wurden und die resultierende Mischung dann zu Körnern getrocknet wurde und die Körner dann mit einer Zweischicht-Tablettenpresse zu einer Zweischicht-Pastille gepresst wurden.
     
    5. Anhaftende Pastille nach Anspruch 1, bei der Partikel von Kalziumkarbonat mit Partikeln des Akaziengummis nass gemischt wurden und die resultierende Mischung dann zu einer Schicht auf einer Platte ausgebreitet wurde und die Platte dann zu zweischichtigen Pastillen geschnitten wurde.
     
    6. Anhaftende Pastille nach Anspruch 1, bei der Partikel von Kalziumkarbonat mit Akaziengummipartikeln gemischt wurden und die resultierende Mischung dann unter Druck extrudiert wurde, um eine zweischichtige Platte herzustellen, die zu Pastillen geschnitten wurde.
     
    7. Die anhaftende Pastille nach Anspruch 6, die durch Heißpressen der Platte mit Matrizen hergestellt wurde, die die Platte durch Heißquetschen in einzelne Pastillen trennen und dann abkühlen.
     
    8. Die anhaftende Pastille nach Anspruch 1, bei der die Klebeschicht am Gaumendach des Mundes eines Menschen stark genug haftet, um das dreifache Gewicht der Pastille gegen die Schwerkraft zu halten.
     
    9. Die anhaftende Pastille nach Anspruch 1, bei der die Klebeschicht am Gaumendach eines Menschen stark genug anhaftet, um das Gewicht der Pastille plus weitere 680 Milligramm gegen die Schwerkraft zu halten.
     
    10. Die anhaftende Pastille nach Anspruch 1, die zwei Seiten hat, die folgendes umfassen

    (a) eine erste Schicht, die nahezu scheibenförmig ist und eine nahezu flache Seite von mindestens 5 mm in zwei Dimensionen hat, die einen Inhaltsstoff enthält, der in den Speichel abgegeben werden soll;

    (b) Bilden einer zweiten, klebenden Schicht, die nahezu scheibenförmig ist und eine nahezu flache Seite von mindestens 5 mm in zwei Dimensionen aufweist, die mindestens 80% Akaziengummi gemischt mit bis zu 20% Alkalisierungsmittel, das als Kalziumkarbonat ausgewählt ist, enthält und einen pH-Wert der Mischung von 5,5 oder höher ergibt, wenn sie in 10 Teilen Wasser gelöst wird; und

    (c) die Schichten Seite an Seite so aneinander zu kleben, dass eine erste ganze Seite der resultierenden Pastille klebend ist und eine zweite ganze Seite der resultierenden Pastille nicht klebend ist.


     
    11. Die anhaftende Pastille nach Anspruch 10 mit mindestens 5 mm in zwei Dimensionen, die, wenn sie in einem menschlichen Mund gehalten wird, als ein einziger Gegenstand, der nicht verschmiert oder auseinanderbricht, im Mund klebt und dort verbleibt, umfasst:

    (a) eine erste Schicht mit einem in den Speichel freizusetzenden Inhaltsstoff; und

    (b) eine zweite, klebende Schicht, die mindestens 80 % Akaziengummi gemischt mit und bis zu 20 % Alkalisierungsmittel enthält, das als Kalziumkarbonat ausgewählt wurde und einen pH-Wert der Mischung von 5,5 oder höher ergibt, wenn es in 10 Teilen Wasser gelöst wird.


     


    Revendications

    1. Pastille adhérente possédant deux côtés, qui lorsqu'elle est maintenue dans une bouche humaine, adhère et reste dans la bouche en tant qu'élément individuel qui ne tache pas ni ne se casse, fabriquée par un processus comprenant :

    (a) la formation d'une première couche, approximativement en forme de disque et possédant un côté approximativement plat d'au moins 5 mm en deux dimensions, comprenant un ingrédient destiné à être libéré dans la salive ;

    (b) la formation d'une seconde couche adhésive, approximativement en forme de disque et possédant un côté approximativement plat d'au moins 5 mm en deux dimensions, comprenant au moins 80 % de gomme d'acacia mélangée avec jusqu'à 20 % d'alcalinisant sélectionné pour être du carbonate de calcium et rendant un pH du mélange de 5,5 ou supérieur lorsqu'il est dissous dans 10 volumes d'eau ; et

    (c) l'adhésion des couches l'une à l'autre, côté sur côté, de sorte qu'un premier côté entier de la pastille en résultant est adhésif et qu'un second côté de la pastille en résultant n'est pas adhésif.


     
    2. Pastille adhérente selon la revendication 1, dans laquelle des particules de carbonate de calcium ont adhéré à des particules de la gomme d'acacia par un processus de granulation mouillé et les particules combinées en résultant ont été ensuite comprimées en une pastille bicouches avec une compression de comprimé bicouches.
     
    3. Pastille adhérente selon la revendication 1, dans laquelle des particules de carbonate de calcium ont été mélangées à sec à des particules de la gomme d'acacia et le mélange en résultant a été ensuite comprimé en une pastille bicouches avec une compression de comprimé bicouches.
     
    4. Pastille adhérente selon la revendication 1, dans laquelle des particules de carbonate de calcium ont été mélangées à l'état mouillé à des particules de la gomme d'acacia et le mélange en résultant a été ensuite séché en des granulés et les granulés ont été ensuite comprimés en une pastille bicouches avec une compression de comprimé bicouches.
     
    5. Pastille adhérente selon la revendication 1, dans laquelle des particules de carbonate de calcium ont été mélangées à l'état mouillé à des particules de la gomme d'acacia et le mélange en résultant a été ensuite diffusé en une couche sur une feuille et la feuille a été ensuite découpée en une pastille bicouches.
     
    6. Pastille adhérente selon la revendication 1, dans laquelle des particules de carbonate de calcium ont été mélangées à des particules de la gomme d'acacia et le mélange en résultant a été ensuite extrudé sous pression afin de fabriquer une feuille bicouches qui a été découpé en pastilles.
     
    7. Pastille adhérente selon la revendication 6, fabriquée par pression à chaud de la feuille avec des matrices qui écrasent à chaud la feuille pour la séparer en des pastilles individuelles, puis par refroidissement.
     
    8. Pastille adhérente selon la revendication 1, dans laquelle la couche adhésive adhère à un palais d'une bouche d'un humain assez fort pour retenir le triple du poids de la pastille contre la force de gravité.
     
    9. Pastille adhérente selon la revendication 1, dans laquelle la couche adhésive adhère à un palais d'une bouche d'un humain assez fort pour retenir le poids de la pastille plus 680 milligrammes supplémentaires contre la force de gravité.
     
    10. Pastille adhérente obtenue selon la revendication 1 et possédant deux côtés comprenant :

    (a) une première couche, approximativement en forme de disque et possédant un côté approximativement plat d'au moins 5 mm en deux dimensions, comprenant un ingrédient destiné à être libéré dans la salive ;

    (b) une seconde couche adhésive, approximativement en forme de disque et possédant un côté approximativement plat d'au moins 5 mm en deux dimensions, comprenant au moins 80 % de gomme d'acacia mélangée avec jusqu'à 20 % d'alcalinisant sélectionné pour être du carbonate de calcium et rendant un pH du mélange de 5,5 ou supérieur lorsqu'il est dissous dans 10 volumes d'eau ; et

    (c) les couches adhérant l'une à l'autre, côté sur côté, de sorte qu'un premier côté entier de la pastille en résultant est adhésif et qu'un second côté de la pastille en résultant n'est pas adhésif.


     
    11. Pastille adhérente selon la revendication 10, possédant au moins 5 mm en deux dimensions, qui lorsqu'elle est maintenue dans une bouche humaine, adhère et reste dans la bouche en tant qu'élément individuel qui ne tache pas ni ne se casse, comprenant :

    (a) une première couche comprenant un ingrédient destiné à être libéré dans la salive ; et

    (b) une seconde couche adhésive, comprenant au moins 80 % de gomme d'acacia mélangée avec jusqu'à 20 % d'alcalinisant sélectionné pour être du carbonate de calcium et rendant un pH du mélange de 5,5 ou supérieur lorsqu'il est dissous dans 10 volumes d'eau.


     




    Drawing








    Cited references

    REFERENCES CITED IN THE DESCRIPTION



    This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

    Patent documents cited in the description