DE1443359B - Process for the production of high molecular weight hydrophilic crosslinking products of polysaccharides or their den vates or of polyvinyl alcohol in the form of gel grains - Google Patents

Description

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The invention relates to a method for producing a number of identical units to form one

of high molecular weight hydrophilic crosslinking per single molecule is obtained, with both poly-

products of polysaccharides or their derivatives, merization and condensation reactions take place.

who cannot find dissociable groups but can find free hy-

contain hydroxyl groups, or from polyvinyl alcohol 5 The alkaline substance that

in the form of gel grains by reaction of the setting required is usually in the solution

cross-linking compound with a divalent organ to be cross-linked compound; it is

niche compound of the general formula, however, also possible, the alkaline reacting sub-

punch in the liquid that is the continuous phase

'ίο forms the two-phase system. She may

in which R is an aliphatic radical with 3 to 10 carbon atoms but not the formation of the two-phase system and JX and Z each prevent halogen or after they joint to initiate crosslinking with two neighboring carbon atoms reacts in dissolved form in the two-phase system of the radical R are an oxirane group, was introduced when crosslinking.

in the presence of an alkaline reacting sub- 15 In principle, any substance that is alkaline in solution can

punch with the formation of ether bridges with the hygienic properties, used for the implementation

hydroxyl groups of the compound to be crosslinked. That will be. The alkali hydroxides, such as sodium hydroxide,

Process is characterized in that one is used particularly frequently. Quaternaries

Dispersion of a liquid solution of the ammonium compounds to be crosslinked, alkali and alkaline earth carbons

Compound in one with this solution not miscible 20 carbonates and alkaline earth hydroxides can also

dispersant can be used under sufficiently strong.

Stir that the solution is in the form of drops in order to carry out the reaction according to the invention .

Dispersant is suspended, with the verre, it is advisable to mix a solution of the alkaline \\

wetting agent converts to gel formation and the reacting compound and the compound to be crosslinked

gel compound formed from the suspended droplets with the liquid which serves to produce the

grain wins. continuous phase of the two-phase system

Polysaccharides suitable for this reaction are those with sufficient agitation to produce the

z. B. dextran, starch, dextrin, cellulose and poly- desired size of the suspended drops

glucose. Suitable derivatives are, for. B. methyldextran, whereupon the crosslinking agent, desired

Ethyldextran, hydroxypropyldextran, methyl cellulose, if necessary in stages, incorporated into the two-phase system.

Ethyl cellulose and ethyl hydroxyethyl cellulose or leads. However, the crosslinking agent can also

Products obtained by partial depolymerization as a solution in the continuous phase

the same are obtained, as well as fractions of this liquid are introduced into the two-phase system.

Links. These starting materials must be free The above-mentioned order of the different

Contain OH groups. 35 which has stages of the method according to the invention

Suitable divalent compounds of the formula have been found to be advantageous in practice; However, it is

XRZ, which in the implementation according to the invention as well as possible, part of the crosslinking agent or

Crosslinking agents can be used are, for. B. the whole amount of the same with the solution of the poly-

Epichlorohydrin, dichlorohydrin, 1,2,3,4-diepoxybutane, to bring meren into contact before the two-phase

bis-epoxypropyl ether, ethylene glycol bis-epoxypropyl 40 system. The gel formation must take so long

ether and 1,4-butanediol-bis-epoxypropyl ether and prevented until the two-phase system is formed

turned connections. would. This can be achieved by

The aliphatic chains that cross-link the mixture at a sufficiently low temperature

Form bridges of the crosslinking product, can keep in temperature, so that the reaction continues so slowly (

be suitably substituted, preferably at 45 steps that the mixing process are carried out

Hydroxy groups and / or interrupted by others. This can also prevent gel formation

Atoms, preferably oxygen atoms. be that one of the alkaline reacting substance

The molecular proportion of the amount to be crosslinked initially retains and only supplies after the

the connection to the crosslinking agent should at least have formed droplets.

1:10. "5 ° For most polysaccharides and derivatives that

The crosslinking agents produced according to the invention as starting material for the products according to the invention if the molecular sieves are to be used in particular, water is a suitable one For whatever purposes they are solvent in the form of gel granules, other liquids are also used will. For this purpose, and this applies to kites with similar dissolving properties as alauch with regard to the other possible feed alcohols and ketones. If desired, options of the crosslinking products are used in the form of solvent mixtures Granules, it is of great importance that the prod- uct water is the main component. If products in this form directly as a result of their alkali hydroxide being an alkaline reacting substance Manufacturing process can be obtained without one wanting to use it as a catalyst or acceptor for Grinding the crosslinking product and then 60 hydrogen halide liberated during the reaction Sieving the ground product is necessary. is used, the alkali hydroxide is added to the water

The object of the present invention was therefore an or the aqueous liquid to dissolve the Process for the immediate production of the pre-crosslinking connection is used. In many The alkali hydroxide facilitates the dissolution of the crosslinking products indicated in the foregoing Comminution of the resulting reaction product 65 to be crosslinked and increases its dissolution makes necessary. opportunity. This is especially true when using dextran

The expression "crosslinking product" denotes and uses starch,

a product that is produced by the chemical reaction of a concentration of the compound to be crosslinked

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is of great importance as it determines the swellability of the dispersed phase. For the professional (Water uptake) of the final crosslinking pro- definitely. One uses a low concentration mixture at different stirring speeds centration of the compound to be crosslinked, so the stirring speed leads to fixed to make the end product more swellable, 5 to achieve the desired result if a higher concentration of the same void is necessary.

is turned. For dextran, the concentration it is often advisable to use the crosslinking agent first

5 to 70 percent by weight, with good results then adding to the system if the appropriate

using concentrations of 10 to drop size is achieved. The necessary for gel formation

50 weight percent were obtained. The time lent for cellulose depends on the content of the

. derivatives can have an even lower concentration bond in the dispersed phase, the amount of

can be used. . Crosslinking agent and the temperature. The Um-

As the continuous phase of the two-phase system of settlement, however, it continues until the mastery Liquids are used that are consumed with wetting agent or the implementation Water or with which is interrupted as a solvent for the .15. After the gelation has taken place Compound used liquid has not found, stirring is none or only are miscible, e.g. B. aliphatic and aromatic of little importance for the particle size of the end hydrocarbons, halogenated aliphatic and valid crosslinking product.

.aromatic hydrocarbons, such as dichloromethane, the reaction temperature determines the speed

1,2-dichloroethane, o-dichlorobenzene and 1,2-dibromine, with which the crosslinking takes place. Suitable

ethane. Temperatures are between room temperature and

To the dispersion of the solution to be crosslinked 90 ° C, preferably between 20 and 60 ° C.
To stabilize the compound is given according to the invention. The property that determines the quality of the crosslinking appropriately a stabilizer for the continuous product as a molecular sieve is its liquid phase forming. As a stabilizer 25 water absorption capacity. The latter is determined by the fact that water-insoluble, high molecular weight poly- mers can be determined by letting the product swell in water, such as polyvinyl acetate, polystyrene, polyisobutylene, and using the remaining free liquid, for example, and cellulose acetate butyrate. That is wisely removed by centrifugation. The water-on-molecular weight of the high molecular weight polymers. would take is expressed as grams of absorbed water per determined to a substantial extent its stable 30 grams of dry matter,
The crosslinking produced according to the invention with relatively high average molecular products were tested as molecular sieves, with the dispersion having otherwise the same excellent results being obtained, which are due to the conditions stabilizing more effectively than the fact that the grains lower average molecular weight sphere. 35 are shaped and therefore have a lower flow-It is advisable to match the amount of stabilizer to the resistance when filling a column with the amount of liquid that is continuous, as columns formed by gel grains of crosslinking phase and the crosslinking agent dissolved products, which contain by grinding or other comminution, or in which it was obtained by the formation of the two-phase process. The system according to the invention is solved. Suitable amounts of the stabilizer produced have proven to be an exceptional sator between 0.1 and 15 ° / ₀ , preferably valuable, especially for the separation of mixtures between 0.1 and 10 ° / ₀ (weight / volume). proven sensitive connections, e.g. B. from

The stabilizer can be separated from the gel grains by treatment with a suitable solvent contained in biological fluids and which separates the separating medium for only one time. When using high molecular weight poly 45 may be exposed for a very limited period of time,
mers which are hydrolyzable under relatively mild conditions, it is advisable to first prepare the gel grains with embodiments of the invention. The specified hydrolyzing agent, for example percentages, are based on weight. The dissolution of alkali hydroxide, treat and then drive is carried out at normal pressure. The weight of the gel grains given in the examples in the hydrolyzed products by washing the gel-5 ° with a solvent for these products refers to the dry weight of the gel grains before removal. High molecular weight esters, such as polyvinyl acetate of the swelling,
and cellulose acetate butyrate, can be used to saponify the ice cream ο ie 1 1
Ester with an aqueous, low-percentage solution

of an alkali hydroxide, whereupon 55 dextran with an average molecular weight (M _w )

the high molecular weight alcohols formed by 40 000 is moistened with about 20% water,

Washing with a suitable solvent is removed and the mixture is washed with a 6N aqueous solution

will. added by sodium hydroxide. Forms after 1 hour

Under certain conditions it is advisable to use a non-lumpy solution. The amount of

surfactant to the reaction mixture to 60 6N sodium hydroxide is adjusted so that the

give. Although such agents do not act as a stabilizer, the concentration of the solution is 40%,

Sators for suspensions, however, can be combined in 600 g of the dextran solution obtained in one

nation can be used with such stabilizers, cylinfalls equipped with stirrer and thermometer you have special effects, e.g. B. smaller particulate drisches reaction vessel poured. As a stabilizer sizes of the crosslinking product, wants to get. In the 65 for the suspension, 20 g of polyvinyl acetate are added The first stage of crosslinking is stirring at an average molecular weight of especially important because this and the presence of 430,000 added, which are dissolved in 500 ecm of toluene, of the stabilizer the size of the liquid droplets - the latter serving as the suspension medium. the

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The stirrer is activated and has an average molecular weight of 40,000

speed adjusted so that the aqueous phase has in. 480 g of this solution are used in Example 1

In the form of small drops inside the toluene phase, the cylindrical reaction vessel described is given, and

is dispersed. Then 50 g of epichlorohydrin, the solution is mixed with 70 ecm of epichlorohydrin

added as a crosslinking agent. The obtained reactant 5 wetting agent and 20 g of polyvinyl acetate after addition

tion mixture is stirred at 50 ° C until game 1 is added as a suspension stabilizer, which in

Epichlorohydrin is essentially implemented. 500 ecm of dichloromethane are dissolved. The networking

The course of the reaction is controlled by the fact that the reaction is carried out at 50 ° C, and it becomes a

once an hour samples from the reaction mixture almost quantitative yield of the dextran crosslinking

be taken, the epichlorohydrin content io product obtained with epichlorohydrin, the

is determined in the samples after the water absorption therein is 2.8 g / g of dry matter,

suspended grains had been separated. Already size distribution of the gel granules:

after a reaction time of 1 hour, a gel 85%, which passes through a sieve with 400 mesh / cm ²

education takes place. _hen

When the reaction is complete, the suspension becomes 15.
worked up. The suspending agent is from the example
Gel grains are filtered off, and the suspension stabilizer. In a similar manner to Example 1, one is washed out with toluene. Prepared by washing with aqueous, 40 ° / ₀ solution of dextran having a through alcohol to remove the solvent and subsequently-average molecular weight of 40 000 closing washing with water until neutral 20,480 g of this solution is in a cylindrical reac reaction the copolymer obtained was added to a vessel and dried ^{with 70 ecm epichlorohydrin as HO 0 C.} The mixed crosslinking agent and 20 g of polyvinyl acetate calculated on the basis of dextran according to the yield of copolymers is essentially quantitative. game 1 added as a suspension stabilizer, wherein

The gel granules of the crosslinking product from both are dissolved in 500 ecm 1,2-dibromoethane. the

Dextran and epichlorohydrin are used to determine the 25 crosslinking reaction is carried out ^{at 50 ° C. and}

sieved their size, and the water absorption is an almost quantitative yield of the dextran

also determined. Crosslinking product with epichlorohydrin with a

y-, ■■ r. j π ■■, water absorption of 3.2 g / g of dry matter.

Size of the grains:

50% passed through a 108 to 400 mesh / ₃₀ B sieve ρ ie 1 5

cm ² go; I _n a similar manner as is in Example 1, a

36%, the / aqueous through a sieve of 400 to 1600 mesh, 40 ° / ₀ solution of dextran having a

cm ² go; average molecular weight of 40,000

Water absorption · provided. 240 g of this solution are in a cylindrical

". ,, ',, 35 reaction vessel and 35 ecm epichloro

3.0 g / g of dry matter. _{hydrin as a} crosslinking agent and 2.5 g of polyvinyl acetate

B e i s e 1 2 added as a suspension stabilizer according to Example 1,

both of which are dissolved in 500 ecm 1,2-dichloroethane.

The crosslinking reaction is carried out ^{at 50 °} C. in a manner similar to that in Example 1

aqueous, 40 ° / ₀ solution of a dextran formed, the 40 and gives a nearly quantitative yield of

an average molecular weight of 40,000 crosslinking product of dextran with epichloro

has. hydrin with a water absorption of 2.5 g / g of the

480 g of this solution are in the cylindrical dry matter.

Into a vessel and the solution is added at 84 ecm .-, .. "·, _, ~" ..,

Epichlorohydrin as a crosslinking agent and 30 g of the 45 S ^{Großenverteilun the} Gelkornchen:

Example 1 described polyvinyl acetate as suspension 56%, which through a sieve with 108 to 400 mesh /

sion stabilizer added, which go in 500 ecm o-dichloro cm ² ;

benzene are dissolved as a suspending agent, whereupon the 20%, which through a sieve with 400 to 1600 mesh /

Implementation is carried out at 50 ° C and one cm ² go,

almost quantitative yield of the crosslinking product.

tes is obtained from dextran and epichlorohydrin. Example 6

The gel granules of the crosslinking product from It becomes a solution of a dextran with a

Dextran and epichlorohydrin are used to determine average molecular weight of 40,000

sieved their size, and the water uptake is dissolving 120 g of the dextran in 800 ecm of water and

also determined. 55 Addition of 60 ecm of an aqueous, 5N solution of

_, .. ".. Sodium hydroxide made. The one made in this way

Size distribution: Dextran solution has a concentration of 14% (Ge

22% passing through a sieve with 180 to 400 mesh / weight / volume).

go cm; A solution of 15 g of cellulose acetate 53%, which is passed through a sieve with 400 to 1600 mesh / 60 butyrate in 500 ecm of ethylene chloride, is then prepared. The cm ² go; The solution obtained is placed in a 2-1 wide-necked round water-receiving flask which is provided with a stirrer and thermometer "", j "",. The temperature of the solution is increased to 2.2 g / g of dry matter. _{approx. 50} o _{c and the driving speed} j _gke jt I _u f 200 rev /

Beisniel 3 ^6s ^ ' ⁿ ' set · The dextran solution is then after

and after to the solution of the high molecular weight

In a manner similar to Example 1, a bond is made in ethylene dichloride. 1 hour after 40% aqueous solution of a dextran formed that. the addition of all of the dextran solution will form

even drops, which can be determined by examining samples taken. Then 10 cc of epichlorohydrin are added, and the reaction is carried out overnight at 50 ⁰ C. Gel formation takes place after 2 hours.

In the morning of the following day, the reaction is stopped, whereupon acetone is added to the reaction mixture. After decanting the solvent from the gel granules, add an additional amount of acetone and decant to remove essentially all of the cellulose acetate butyrate. In order to remove the film of the stabilizer surrounding the grains, the grains are made in a solution ^! 50 parts of an aqueous 2η solution of sodium hydroxide and 50 parts of 95% ethyl alcohol are dispersed. After treating the gel granules for 15 minutes, a dilute hydrochloric acid solution is added to neutralize the granules and the mixture is filtered. The gel grains are allowed to swell out by treatment with ethyl alcohol and they are finally dried at 70.degree. C. in a vacuum.

The crosslinking product contains 10 ° / ₀ acetone. The yield, calculated as acetone-free material, is 90 g. The water uptake is 19.2 g of the dry product and the swelling factor is 38 cem / g of the dry product.

Distribution of size:

6.2 ° / _0, which pass through a sieve of 1600-6560 stitches / cm ^2;

51.5% that will pass a 6560 to 11,500 mesh / cm ² screen;

40.2% that will pass a 11,500 to 22,500 mesh / cm ² screen;

2.1% that go through a sieve with <22,500 meshes / cm ² .

Example 7

100 g of dextrin, produced by hydrolysis of starch under acidic conditions, are in a Solution of 200 ecm of water and 125 ecm of aqueous 5N sodium hydroxide solution dissolved, and the resulting The solution is dispersed in a solution of 15 g of cellulose acetate butyrate in 500 ecm of ethylene dichloride at 50 ° C. 40 cc of epichlorohydrin is added to the dispersion as a crosslinking agent, and the crosslinking reaction is carried out at 50 ° C. for 18 hours. To Cleaning and drying according to Example 6 gives 100 g of a product with a water absorption which 4.8 g / g of the dry product.

Size distribution:

24% that will pass a 1600 to 6560 mesh / cm ² screen;

66% passing a 6560 to 22,500 mesh / cm ² screen;

10% that go through a sieve with <22,500 meshes / cm ² .

Examples

120 g of dextran with an average molecular weight of 20,000 are mixed with 80 ecm of water moistened, and the mixture obtained is with 95 ecm of an aqueous 5N sodium hydroxide solution added to obtain an aqueous dextran solution.

TVp T ö <: rmfT ivnrrlp in pir> pr T ncnincr vnti 1 O <r 7V11-n1rtcp_ acetate butyrate dispersed in 250 ecm of ethylene dichloride. The dispersion is heated to 50 ° C., and at this temperature 80 g of ethylene glycol diglycidether are added, whereupon the mixture is reacted for 18 hours.

After working up and drying according to Example 6, 157 g of a crosslinking product with a Water absorption, which is 2.1 g / g of the dry product. .

Distribution of size:

15 g passed through a 108 to 400 mesh /

cm ² go; ·

102 g passed through a 400 to 1600 mesh /. cm ² go; .

31 g passed through a 1600 to 6560 mesh /

cm ² go;

6 g that go through a sieve with <6560 mesh / cm ² .

B e i s ρ i e 1 9

120 g of 2-hydroxypropyldextran (average molecular weight 5 · 10 ⁵ ) are dissolved in 200 ml of water, and 60 ml of aqueous 5N sodium hydroxide solution are added to the solution. The solution obtained is in a solution of 10 g of cellulose acetate butyrate in 250 ecm of ethylene dichloride at a temperature. dispersed at 50 ° C. 10 ecm of epichlorohydrin are added, and the reaction "is carried out at this temperature for 18 hours. I.,.,

After working up the "reaction mixture and drying the reaction product according to Example $ , 102 g of a crosslinking product composed of 2-hydroxypropyldextran and epichlorohydrin with a water absorption that is 7.3 g / g of the dry product" are obtained. ";;; yy '/' /.

Distribution of size: .. ;;; ■ ".

5 g, ⁱ go through a sieve mii 400 to 160Ö meshes / cm ^2; . ^ V '\, "'

60 g passed through a sieve with ί 600 to 11500 mesh /

cm ² go; "

36 g that go through a sieve with i:. <Ll 500 meshes / cm ² . . ', J "■ _.

Example 10

60 g of ethyl hydroxyethyl cellulose are dissolved in 350 ecm of water, and 30 ecm of one are added to the solution given aqueous 5N sodium hydroxide solution. The resulting solution is in a solution of 10 g Cellulose acetate butyrate is dispersed in 250 ecm of ethylene dichloride, followed by 10 ecm of epichlorohydrin as a crosslinking agent be added. The suspension is heated to 50 ° C. and at this temperature for 18 hours held, whereupon the reaction mixture is worked up and the gel granules are dried. Man receives 43 g of a crosslinking product from ethyl hydroxyethyl cellulose and epichlorohydrin with a Water absorption, which is 7.1 g / g of the dry product.

Distribution of size: ^r '.

8 g that will pass through a screen of 1600 to 11500 mesh / cm ² ;

27 g passing through a 11,500 to 22,500 mesh / cm ² screen;
5 g passed through a sieve of 22,500 mesh / cm ²

Example 11

50 g of spray-dried dextran (average molecular weight = 40,000) are dissolved in 50 ml of water, and 4 ml of an aqueous 2N sodium hydroxide solution are added to the resulting solution. The dextran solution is then dispersed in a solution of 3 g of cellulose acetate butyrate in 100 ecm of ethylene dichloride. This dispersion is then mixed with 10 ml of 1.2 to 3.4-diepoxybutane as a crosslinking agent, and the mixture is heated to 50 ⁰ C, after which allowed the reaction to proceed overnight. The reaction mixture is worked up and the gel granules are dried according to Example 1. 50 g of a crosslinking product composed of dextran and 1,2-3,4-diepoxybutane are obtained with a water uptake of 5.0 g / g of the dry product.

Example 12

100 g of starch washed with water are dissolved in 280 ecm of water and 240 ecm of an aqueous 5N sodium hydroxide solution. The solution obtained is dispersed in a solution of 15 g of cellulose acetate butyrate in 500 ecm of ethylene dichloride. After the dispersion had been stirred for 1 hour to stabilize the starch solution droplets in the dispersing medium, 70 g of 1,3-dichloropropanol- (2) are added. The reaction is carried out ^{at 50 ° C. for 10 hours.} After working up the reaction mixture according to Example 6, 93 g of a crosslinking product are obtained in the form of gel grains with a water absorption of 3.3 g / g of the dry product.

Example 13

20 g of polyvinyl alcohol are dissolved in 140 ecm of water and 60 ecm of an aqueous 5N sodium hydroxide solution. The solution obtained is dispersed in a solution of 8 g of cellulose acetate butyrate in 200 ecm of ethylene dichloride. To the obtained dispersion 20 cc of epichlorohydrin are added, and the reaction is carried out for 16 hours at 50 ⁰ C and 4 hours at 70 ⁰ C. After working up the reaction mixture according to Example 6, a crosslinking product is obtained with a water absorption of 9.1 g / g of the dry product.

Grain size distribution:

60% passed through a sieve with 59 to 400 meshes /

cm ² go;
30% that will pass through a 400 to 1600 mesh / cm ² screen;

10% that go through a sieve with> 1600 mesh / cm ² .

Example 14

120 g of dextran (average molecular weight = 40,000) are moistened with 36 ecm of water, whereupon the moistened dextran is dissolved in 144 ecm of an aqueous 3N sodium hydroxide solution. The dextran solution is dispersed in a solution consisting of 300 ecm of ethylene dichloride and 30 g of a 27% solution of polymethyl methacrylate in ethyl acetate. After a stabilization period of 30 minutes 30 cc of epichlorohydrin are added, and the reaction is carried out for 10 hours at 5O ⁰ C. The gel grains obtained are filtered off, washed first with ethylene dichloride and then with 99.5% ethyl alcohol, whereupon they are dispersed three times in water, decanting after each dispersion process. The gel grains are finally allowed to swell out by treatment with 99.5% alcohol. After drying at 60 ° C., the product weighs g and has a water absorption of 6.2 g / g of the dry product.

Example 15

120 g of dextran (average molecular weight = 20,000) are moistened with 30 ecm of water, and the moistened Dextran is dissolved in 120 ecm of an aqueous n-sodium hydroxide solution. The dextran solution is dissolved in a solution of 6 g of polyvinyl butyral

Leres molecular weight = 70,000) were dispersed in 300 cc of ethylene dichloride, 40 cc of epichlorohydrin are added, and the reaction is carried out for 16 hours at 50 ⁰ C. The gel grains are filtered off and dispersed four times in 500 ecm acetone, decanting after each dispersion process. Any remaining polyvinyl butyral is then washed out by dispersing the granules in aqueous 1N hydrochloric acid for 10 minutes. Finally, the crosslinking product is washed with water, left to swell by treatment with 99.5% alcohol and dried. The product obtained weighs g and has a water absorption of 2.5 g / g of the dry product.

Claims (6)

Patent claims: 1. Process for the preparation of high molecular weight hydrophilic crosslinking products of Polysaccharides or their derivatives that have no dissociable groups but free hydroxyl groups contain, or of polyvinyl alcohol in the form of gel grains by reaction of the to crosslinking compound with a divalent organic compound of the general formula XRZ, in which R is an aliphatic radical having 3 to 10 carbon atoms and X and Z are each halogen or together with two adjacent carbon atoms of the radical R an oxirane group are, as a crosslinking agent in the presence of an alkaline substance with the formation of Ether bridges with the hydroxyl groups of the compound to be crosslinked, characterized that a dispersion of a liquid solution of the compound to be crosslinked in one immiscible with this solution Dispersant with sufficient agitation that the solution is in the form of drops in the Dispersant is suspended, reacted with the crosslinking agent until gel formation and the gel grains formed from the suspended droplets are obtained. 2. The method according to claim 1, characterized in that the crosslinking agent in the Bringing preparation of the dispersion with the solution of the compound to be crosslinked in contact. 3. The method according to claim 1 or 2, characterized in that at least part of the Crosslinking agent supplied as a solution in the dispersant. 4. The method according to claim 1, characterized in that there is a solution of the to be crosslinked Compound, the alkaline reacting substance and the crosslinking agent, prior to manufacture of the two-phase system is kept at a sufficiently low temperature to allow gelation to prevent being dispersed in the dispersant. 5. The method according to claim 1 to 4, characterized in that the degree of dispersion by adding 0.1 to 15%, based on the amount of the dispersant, of a high molecular weight Polymer, which is not soluble in the solution of the compound to be crosslinked, regulated. 6. The method according to claim 5, characterized in that one is a high molecular weight polymer used, which can be hydrolyzed under mild conditions.