CS225368B1 - Hydrophilic latex particles containing the aldehyde groups and method of their manufacture - Google Patents

Description

The invention relates to latex particles containing aldehyde groups and to a process for their preparation.

Hydrophilic latex particles find wide application in various fields of biochemistry, especially as carriers of biochemically or immunologically active substances. The prior art methods of synthesizing latex particles capable of binding biochemically or immunologically active substances on their surface consist mainly in standard emulsion polymerization. The principle of conventional emulsion polymerization is generally known and consists in dispersing a water-sparingly soluble monomer or a mixture of water-sparingly soluble monomers in an aqueous emulsifier and initiator solution, heating the mixture to a temperature at which chain polymerization initiating radicals are generated, and maintaining and maintaining this mixture. at the desired temperature with stirring for the time required to achieve a certain conversion. The polymerization itself takes place initially in colloidal formations called micelles (in which the monomer is soluble) formed by suitably spherically arranged surfactant molecules. After the polymerization is complete, the surfactant remains on the surface of the polymeric latex particles formed and thus stabilizes them against coagulation. Although removal of the emulsifier is largely possible, either the irreversible loss of the individual character of the discrete polymer particles by their aggregation during coagulation or at least the impossibility of restoring the particles to their original state occurs. This disadvantage of conventional latexes is eliminated by the use of the so-called emulsion-free emulsion polymerization technique in which the particles are autostabilized by ionogenic groups which are part of the polymer chain formed during the initiation reaction. The most recent example of this polymerization is the method of CS. 225010 describing the synthesis of latex hydrophilic particles by homo- or copolymerization of monomers of the general formula

CH ₂ = _{CRT-X-CH2 -CH-CH2,} \ Z

Where R 1 is hydrogen or methyl and X is -O- or -CO-O in the absence of an emulsifier resulting in spherical polymer particles of the same size. These particles carry a number of reactive epoxy groups that can be used to attach biologically or immunologically active substances to the surface of the particles. The epoxy group undoubtedly fulfills a number of requirements for the synthesis of polymer-active substance conjugates, but its disadvantage is that the reaction itself proceeds relatively slowly. Long incubation may in some cases lead to a loss of biological or immunological activity. This can be avoided by the use of carriers whose functional groups are more reactive compared to the epoxy, i. that under the conditions in which immobilization can be realized due to the stability of immobilized substances, they react more quickly.

The aldehyde groups are capable of reacting with the amino groups of the substance to be immobilized under mild reaction conditions. Thus, for example, amino groups in the side chains of lysine residues in proteins. This reaction proceeds rapidly enough to form an imine bond, which can be reduced to amine by conventional techniques in order to increase its stability.

The present invention relates to hydrophilic latex particles containing aldehyde groups, which consist of a polymer consisting of polymerized units of the general formula I - CH _{2 -} CR ¹ (I),

AND

X-CH _{2 -} CH = O wherein R ¹ is hydrogen or methyl and X is -O- or -CO-O- or from a mixture of the polymerized units of the formula I with 1 to 99% by weight of a compound of formula I; polymerized monomers selected from the group consisting of glycidyl acrylate or methacrylate, styrene, divinylbenzene, hydroalkyl and alkyl acrylates and methacrylates, N-vinylpyrrolidone, vinyl acetate, butadiene, isoprene, acrylamides or methacrylamides and glycidyl vinyl ether.

The invention further provides a process for the preparation of hydrophilic latex particles containing aldehyde groups, comprising latex particles containing polymerized groups alone having two hydroxyl or one hydroxyl and one amino group or a mixture thereof of 1-99% in the side chain of adjacent carbons of the chain wt. polymerized monomers selected from the group consisting of glycidyl acrylate or methacrylate, styrene, divinylbenzene, hydroxyalkyl or alkyl acrylate or methacrylate, N-vinylpyrrolidone, vinyl acetate,

Claims (2)

SUBJECT Hydrophilic latex particles containing aldehyde groups, characterized in that they consist of a polymer composed of polymerized units of the formula I butadiene, isoprene, acrylamides or methacrylamides and glycidyl vinyl ether is mixed with a 1-10 molar excess relative to the vicinal groups content of the periodic or periodate solution and allowed to react at 0 to 50 ° C for up to 50 hours. After completion of the reaction, excess acid and other reaction products are removed by decantation in a centrifuge, by dialysis, by pressure filtration, or by an appropriate method. The product can then be used directly for further processing. In the following, the invention is explained in more detail in the examples. Example 1 20 ml of latex particles suspended in water synthesized from glycidyl methacrylate according to Cs. 225010 was hydrolyzed with 5 ml of aqueous 2 mol / L sodium hydroxide solution for 12 hours at room temperature and then dialyzed for 5 hours against water. 100 mg of sodium periodate was dissolved in the product and the mixture was stirred after adjusting the pH for 3 additional 12 hours and dialyzed against water for 4 hours. The product contains a detectable amount of reactive aldehyde groups. Example 2 20 ml emulsion containing 10% glycidyl acrylate-styrene-divinylbenzene 5: 90: 5 wt. prepared according to Cs. 225010 was mixed with 15 ml of concentrated ammonia solution (25% by weight in water) and allowed to react at 50 ° C for 10 hours. After excess ammonia was distilled off, 5 ml of saturated periodic acid solution was added to the latex and the mixture was heated to 45 ° C for 30 minutes. After removal of undesirable low molecular weight substances, the latex contained particles with aldehyde groups. Example 3 A 20 ml emulsion containing 10% glycidyl vinyl ether-isoprene copolymer particles (15 to 85 wt%) was mixed with 20 ml 0.5 mol / L perchloric acid and stirred at 70 ° C for 10 minutes. The acid was largely removed by centrifugation in a centrifuge, the volume adjusted to 20 ml and 30 mg sodium periodate added and the pH adjusted to 3. At 0 ° C, the mixture was left for 50 hours and then unreacted periodate and low molecular weight reaction products were removed by dialysis against water. The latex particles contained a detectable amount of aldehyde groups. INVENTION -CH ₂ -CR ¹ (I) AND X - CH _{2 -} CH = O wherein R 1 is hydrogen or methyl and X is -O- or -CO-O- or from a mixture of the polymerized units of the formula I with 1 to 99 wt. polymerized monomers selected from the group consisting of glycidyl acrylate or methacrylate, styrene, divinylbenzene, hydroalkyl acrylate and alkyl acrylates and methacrylates, N-vinylpyrrolidone, vinyl acetate, butadiene, isoprene, acrylamides or methacrylamides and glycidyl vinyl ether. 2. A process for the preparation of hydrophilic latex particles containing aldehyde groups, characterized in that the latex particles containing the polymerized groups themselves having two side chain hydroxyl or one hydroxyl groups and one amino group or a mixture thereof with 1 to 99% by weight. of polymerized monomers selected from the group consisting of glycidyl acrylate or methacrylate, styrene, divinylbenzene, hydroxyalkyl acrylate or alkyl acrylate or methacrylate, N-vinylpyrrolidone, vinyl acetate, butadiene, isoprene, acrylamides or methacrylamides, or periodate in water and allowed to react at 0 to 50 ° C for up to 50 hours.