Method of preparation of an aqueous absorbent colloid dispersion.

PATENT AS AFRICAN AND MALAGASY

INDUSTRIAL PROPERTY

P. 887

international Patent Classification yaoundê (Cameroon): 01 - c 10 no. 02321 b.

O ^ ^ Ρ Α Μ. THE I.

V

10 To 20 hr 13 February 1967 request rn

the O.A.M.P.I. (G.P. no. 52,757) by

the sosiété said: FAEBWEEKE and Hoechst AKTCENGESELLSCHAFTVormals set limits Lucius Richard & BEUNING, residing in Germany.

5 May 1970 delivered

Publishes official ballot № 1 of 1970

PRIORITY:

Requests for patents in Germany under the n°

F. 24857 IVB of/12/and f 25921 IVB of P-P of 22 January 1958 l2

7 june 19588 and on behalf of the applicant.

A method of preparing an aqueous dispersion of hydrophilic colloids.

The applicant has found that one can provide hydrophilic colloids of interest to the industry by subjecting collagen breakdown products to hydrolytic degradation provided to an

5 2,000 to 20,000 molecular, 5,000 to 10,000 preferably, then rêticulant hydrolysate with a polyfunctional isocyanate, the amount of isocyanate used is less than the amount calculated based on the number of amine groups and guanidine groups contained in the hydrolysate and representing 10 preferably 20 to 80 the I " of this amount, by adjusting the pïï it at a pH of about 7 and adding the solution sodium chloride in an amount of about 9 grams per liter, or in the rêticulant collagen breakdown products with a polyfunctional isocyanate applied in an

15 amount representing 20 to 80# of the calculated amount and according to the number of amine groups and guanidine groups present, followed by subjecting the product of cross-linking to a hydrolysis to a molecular weight of 10,000 to 100,000, preferably 50,000 to 60,000 by adjusting the pH of the solution 20 obtained at pH 7 and adding to the solution of the sodium chloride in an amount of about 9 grams per liter.

SSO procedures differ from each other by the order

of succession of stages. In the first operating mode, the starting material is first degraded into smaller molecules which are then crosslinked by a polyfunctional isocyanate to form molecules of the desired magnitude, while in the second the starting material is first crosslinked to form even larger molecules which are then degraded at the desired magnitude.

In both operating modes, the effect of cross-linking is

the same. the " blocking amino groups or guanidine groups in the final products by the bridges formed using urea isocyanate, moves the ratio of free carboxyl groups to amino groups in favor of the first, resulting in increased the solubility and reduced ability to gel. The bridges of urea, newly formed by cross-linking between different molecules, are not broken in the mild conditions is carried out for the hydrolysis;

there is a cleavage of peptide bonds between protein chains.

Removing material can be used as a starting material the mineral constituents annoying, especially the calcium salts, by dialysis, electro-dialysis, or, better, by treatment with an ion exchanger.

The products obtained according to this method have branched molecules having a large burden.

The degradation of gelatin or collagen breakdown products which must first be performed according to the first operating mode, can be performed in several ways, for example by acid hydrolysis, alkaline or by fermentation. May be hydrolyzed gelatin a especially gently by heating in aqueous solution to about neutral reaction, to a temperature between 60 and 150 degrees, preferably to 120° until is reached the degree of hydrolysis desired corresponding to a molecular weight of 2.000 20 to 000. For good bone gelatin, heating about five to six hours to 120 Degrees, in closed container, is sufficient to achieve a degradation corresponding to molecular weights of 5,000 to 10,000. The concentration of gelatin is preferably of about 4 - 6 $, however hydrolytic degradation and the subsequent cross-linking can be carried out also at concentrations below or above,

Reacting hydrolysate with the polyfunctional isocyanates may be performed immediately after the hydrolysis and in the same solution. Under these conditions the group isocyanic preferably reacts with the. reactive amine groups or with groups or guanidine amidated peptide chains, by creating groups of urea. There is a resulting urea cross-linking bridges between two or more polypeptide chains which leads to a 'molecule' larger. When using a di-isocyanate, the réactionpeut be illustrated by the following scheme:

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The cross-linking reaction is carried out preferably in neutral or weakly alkaline, because, in acidic solution, the reaction proceeds very slowly or does not take place at all.

Since the basic amino groups become, during the reaction, urea groups in very weakly basic, carboxylic groups present from sdus form inner salts are released and the pH moves towards acidic.

For this reason it is appropriate to adjust pH in accordance with consumption of isocyanate, by continuously adding dilute alkali and thereby maintaining the pH to a value between 7 and 8.

The isocyanate is added, preferably by stirring the solution vigorously, either directly or dissolved in an organic solvent miscible with water and inert to isocyanate, as for example the têtrahydrofurane or acetone. The temperature of the solution can vary widely, and 100 degrees between 0°;

preferably the working temperature is of 30°. The isocyanate is added in portions at best; then it follows the course of the reaction by the variation in pH or by the consomnation alkali mentioned above. As isocyanate can be taken e.g. aliphatic polyisocyanates, especially those of the type 00 - Η (0 Η) - the ICO,, where X is a number between 2 and 20, or also poly-aromatic isocyanates or hydro-aromatic.

The amount of isocyanate most favorable for the cross-linking depends on the size of molecules of the hydrolysate and also the quality of the starting material; it may represent 10 to 100 $amount that is determined from the results of the assay of the KH groups. From a hydrolysate of a molecular weight of 5 000 - 10 000, products are obtained particularly suitable if uses about 30 to 40 The O/degrees the amount of polyfunctional isocyanate which was evaluated based on the content of amino groups or guanidine in accordance with the amino acid composition of gelatin or based on the degree of hydrolysis. After the cross-linking invention aims to eliminate the organic solvent of the final product ultimately used to. dissolving the isocyanate. Particularly advantageous is this removal by distillation under reduced pressure by adding a small amount of an anti-foaming agent, such as octyl alcohol, for preventing the formation of foam. The defoaming agent is. driven with the water vapor during the distillation.

For 1' use, the solution is brought to a volume such that it contains 5 i° protein. Then adding sufficient sodium chloride in an amount of about 9 grams per liter, also can be prepared by lyophilizing a dry powder must be again dissolved in sterile water for use.

Since the viscosity increases during the cross-linking of collagen breakdown products, preferably gelatin, with the polyfunctional isocyanates, the solution, in the second operating mode sets to a jelly after some time and nor well suited more to continue adding fractionated isocyanate or tuning the pïï after gelation. By dropping for several hours the cross-linking solution following gelation, is carried out in this case also, a total reaction of the isocyanate with the material Hase rêticuler confectioneries.

In the second operating mode also, the isocyanate may be added, with thorough mixing, either directly, wine is dissolved in organic solvent. the degradation of the crosslinked products is carried out in the same manner as in the first operating mode. Is being performed thermally, heating to five to six hours 120° in closed container gives the best results.

the solutions of products produced by both operating modes. Their solutions are " excellent clarity and, unlike other known products prepared from gelatin, they are also colorless; the solidification point is less than 10°. The molecular weights of the products according to the invention range from 15,000 to 60,000 and may be adapted SSO molecular weights to practical requirements by varying the conditions of preparation. The products having a molecular weight of about 20,000 were found to be the most appropriate. As determined by ultracentrifugation measurements, the final products have molecules of substantially uniform size.

The following examples illustrate the present invention without limiting its scope scope.

Example 1

Is set to a pïï of 6.9 one liter of an aqueous solution

5 i-<> of bone gelatin, prepared to from 60 grams of a, gelatin to 15.12 the I " moisture and 1.68 with fo ash, and heating to 120° for five and one-half hours in a closed container placed in a steam autoclave. After cooling to about 90° is lifted out of the autoclave vessel and allowed to cool to room temperature. The solution is filtered and summed with the of 9 grams of pure sodium chloride. ^ near have adjusted the pH to about 7, flowed, all

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strongly stirring, a solution of 1.66 cm - hexamêthy

lène diisocyanate in 25 cm of têtrahydrofurane, at a temperature of about 30°. Continually the pH of the solution and held about 7 by adding dilute caustic soda. After three hours the reaction is complete. To remove têtrahydrofurane solution is concentrated to half under reduced pressure after adding several drops of octyl alcohol for preventing foam; octyl alcohol added is driven during the distillation. Extended again the solution to

1 liter with water and the filter optionally once again. The solution being in vials or ampules. May be added sodium chloride to the solution from the beginning, prior to degradation of the gelatin, or at the end. Instead of the têtrahydrofurane might be used in acetone to dissolve hexamethylene diisocyanate.

2 Exemule

Subjecting 1 liter of a gelatin solution to 5 % to degradation by heating to 120° as to 1' example 1, is

then adds a suspension of hexa-methylene - 1.66 cm

3

diisocyanate in 30 cm of water and is allowed to make the cross-linking by vigorous agitation to the EH 30° and maintaining the pH at about 7 by continuously adding dilute sodium hydroxide solution. When the pH does not change anymore, the reaction is complete. If necessary the solution is filtered, added 9 grams of pure sodium chloride, is placed in ampoules or vials.

Example 3

Adjusted to pH 7, 2 liters of an aqueous solution at 5 the I " of bone gelatin. Then pour at 30 degrees, under vigorous stirring, 3.32 cm/of hexamethylene diisocyanate dissolved in 25 cm of têtrahydrofurane. During the cross-linking reaction that takes place in the viscosity increases more and more until the solution is solidified into a jelly, what happens at the end of half an hour. The stirring is stopped and allowed to sit for another fifteen hours at ambient temperature. Followed by heating the frozen 120° for five and one-half hours in closed container.

With the solution which is added to the evaporated 18 grams of sodium chloride and, to remove têtrahydrofurane, it is concentrated under reduced pressure to 2/3 of its volume primitive. For preventing foam can then add octyl alcohol which is driven during the distillation. By extending the solution volume primitive with water, the pH is adjusted to 7 optionally is brought about and the