Hydrophilic copolymer gels, pharmaceutical compositions, pesticidal compositions & fragrance compositions

© Start of patent period: 1976 09 15 Longest possible duration:

© Published on: 1977 05 25 © inventor:

© dependence:

© Pamphlets considered to delineate the prior art:

Nr.336891

The invention relates to a process for the preparation of crosslinked hydrophilic polymers which are suitable for use as carriers for medicaments and other active substances; furthermore as hydrophilic membranes for separation processes, as wound dressings, as body implants, for example artificial veins; as cover layers for glass, metal, wood or ceramic and in particular for use in cases where simultaneously

Strength and high water permeability of the polymer article are required.

It is known, weakly crosslinked, water-insoluble, but hydrophilic polymers as a carrier material for biologically active, at least slightly water-soluble substances by copolymerization of a predominant proportion of hydrophilic mono-olefinic monomers and a small proportion, between 0.01 and 15%, based on said mono -olefinic monomers to be derived from a low molecular weight crosslinking agent. Mono-olefinic monomers used are, in particular, monoesters of acrylic or methacrylic acid with polyfunctional alcohols, such as, for example, ethylene glycol mono-methacrylate, and as crosslinking agents, in particular diesters of the acids mentioned with the alcohols mentioned, such as, for example, ethylene glycol bis-methacrylate, and the copolymerization is in the presence of water, s. U.S. Pat. No. 3,220,960 or in an anhydrous system, s. U.S. Pat. No. 3,520,949. Both low molecular weight and macromolecular, water-soluble compounds, such as Polyäthylenoxydmono-methacrylate together with a small amount of the corresponding bis-methacrylate were used according to the US Pat. No. 3,220,960 as monomers and crosslinking agent. The water-insoluble but hydrophilic copolymers and their method of preparation have been modified in various ways and adapted to particular needs, eg for the production of soft contact lenses (US Pat

No. 3,200,960 and Reissue No. 27,401) and the copolymerization in the presence of linear polyamide resin in order to improve or modify the mechanical properties of articles formed from polymers obtained in this way (US Pat. No. 3,520,949). Nevertheless, in all embodiments, low molecular weight polyolefinic crosslinking agents, in particular ethylene glycol bis-methacrylate, were used u.zw .. in very small to moderate amounts, never exceeding 20% ​​of the mono-olefinic monomer content.

Although the copolymers of the type described above could be adapted to the various usage requirements, it was not possible to satisfactorily adapt the mechanical properties to all uses in both the unswollen, ie anhydrous, and the swollen, ie in equilibrium with water state.

It is known that hydrophilic polymers whose main components are monoesters of acrylic acid and

Methacrylic acid and a bifunctional alcohol, glass transition temperatures or softening points between 55 and 80 ° C have. For this reason, articles which are state of the art are brittle and glass-like at temperatures below 55 ° C. in the dry state. After reaching the state of equilibrium in water, the objects mentioned in the prior art become soft and deformable, but also weak in terms of flexural strength; In addition, they have low tear and shear strength, which makes them sensitive to kinking or other stress. To avoid these undesirable adverse properties of the prior art articles, they are reinforced by inserts of stronger polymeric material, or the prepolymerized mixture is filled with an insoluble material such as silica gel. While these aids to some extent enhance toughness (cohesive forces) (because the hydrogel acts as a putty), the articles thus obtained in the dry state are prone to glassy breakage and shear failure in the swollen state in the constrictions (spaces) of these articles , Another disadvantage is the addition of filler to the prepolymer by the diffusion properties and the water permeability of the article are changed.

Subject of the invention

The invention relates, inter alia, to the preparation of cross-linked hydrophilic copolymers having high flexibility and elasticity both predominantly anhydrous and in the swollen state, ie in equilibrium with water or aqueous liquids, such as body fluids. These copolymers are suitable for use as hydrophilic membranes in separation processes, as wound dressings, body implants, eg artificial veins, further as cover layers on glass, metal, wood or ceramic, and as a carrier material for biologically active compounds, for example medicaments, herbicides, insecticides, fungicides, bactericides and fragrances.

Another object of the invention is the preparation of crosslinked hydrophilic copolymers with high tensile strength in the quenched state for the purposes defined above.

Another object of the invention is the preparation of crosslinked hydrophilic copolymers having the above-mentioned improved properties, with a variable, effective content of biologically active material, in particular of therapeutically active substances.

It has now been found that water-insoluble hydrophilic copolymers, which consist predominantly of a hydrophilic polymer of mono-olefinic monomers, which are crosslinked with a predominant proportion of a diolefinic, non-hydrophilic macromers and which ent3 a biologically active substance

No.33 6891, which possess the abovementioned and other desirable properties. In the novel copolymers, the proportion of terminal diolefinic macromer is higher than that of crosslinking agents in the known hydrophilic copolymers, and it is a predominant portion of the system having from about 10 to about 70% of the hydrophilic polymer, or preferably from about 15 to about 50% of the same. The said terminal diolefinic non-hydrophilic macromer has a molecular weight between about 400 and about 8,000, or preferably between about 600 and 5000.

In particular, the invention encompasses an insoluble polymeric hydrogel which is useful as a carrier for drugs administered orally or buccally (through the mouth) or in the form of subcutaneous or intramuscular implants. The hydrogels of the present invention may also be molded into body implants, such as artificial veins, urethral, ​​vaginal, or gut outlet devices, or may be used in the form of dressings for the controlled delivery of drugs through the skin. Other applications of the new water-swellable gels are reverse osmosis membranes or semi-permeable membranes; hydrophilic membranes for separation processes; Dressings for wound treatment; Topcoats on glass, metal, wood or ceramic and, more generally, applications where both hydrophilicity and toughness are required simultaneously.

The novel hydrogels according to the invention are prepared in the presence or absence of solvents by free radical copolymerization of a water-soluble monomer (As) capable of forming a water-soluble or water-swellable polymer, ie, a hydrophilic polymer (Ap) di-olefinic non-hydrophilic macromers (B), eg a divinyl compound with a long, linear polycondensate chain, such as Polytetramethylene ether, having a polymerizable vinyl group terminal on both sides. In this way, a three-dimensional macromolecular network is formed, which is composed of two types of segments, each segment contributing its particular physical properties to the whole system. The A segment confers water solubility, the hydrophobic B segment forms the flexible crosslinks. By altering the respective Meng conditions of each compound, the mechanical and diffusion properties can be varied within a wide range. For example, a polymer with excellent toughness, strength and ductility can be obtained, which nevertheless can approximately absorb its own weight of water; this polymer is available using the appropriate proportions of A and B. This possibility is not present in known hydrogels, because their crosslinks are short and inelastic, and these Hydro30 gels are hard and brittle in the dry state »

The incorporation of the bifunctional macromolecule B in a predominantly quantitative ratio into the system is novel in the polymers according to the invention. In this way, the bifunctional macromer serves not only as a structural crosslinker, but also as an agent of unique physical properties to the gel.

The hydrophilic polymer is preferably a polymer of one or more water-soluble mono-olefinic monomers, As, but it may also be a copolymer of a mono-olefinic water-soluble monomer and at most 70%, preferably at most 50% of the total amount of the monomer, of a water-insoluble mono- be olefinic monomers. The water-soluble monomers are preferably acrylic and / or methacrylic acid (2-methylacrylic acid) or water-soluble derivatives thereof, such as

for example, their hydroxyalkyl esters, for example 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl or 2,3-dihydroxypropyl esters; also ethoxylated and polyethoxylated hydroxyalkyl esters, such as esters of alcohols of the formula

HO-C H - O- (CH-CHO) -R, m 2m 2 2 ^zn 'in which R is hydrogen or methyl, m is 2 to 5 and η is 1 to 20, or esters of analogous alcohols in which a part of the Äthylenoxydeidheit is replaced by propylene oxide units. Further suitable esters are dialkylaminoalkyl acrylates and methacrylates, such as the 2- (dimethylamino) ethyl, 2- (diethylamino) ethyl and 3- (dimethylamino) -2-hydroxypropyl esters. Another class of suitable derivatives of such acids are their water-soluble amides, such as the unsubstituted amides and amides substituted by lower hydroxyalkyl, lower alkyl or lower dialkylaminoalkyl groups, such as N- (hydroxymethyl) -acrylamides and -methacrylamides, N- (3-hydroxypropyl ) -acrylamide, N- (2-hydroxyethyl) -methacrylamide, N- (1, 1-dimethyl-3-axabutyl) -acrylamide and N- [1,1-dimethyl-2- (hydroxymethyl) -3-oxabutyl] - acrylamide; water-soluble hydrazine derivatives, such as Trialkylamino-methacrylimides, for example trimethylamino-methacrylimides and dimethyl (2-hydroxypropyl) -amino-methacrylimide and the corresponding derivatives of acrylic acid; mono-olefinic sulfonic acids and their salts, such as sodium ethylenesulfonate, sodium styrenesulfonates and 2-acrylamido-2-methylpropanesulfonic acid; N- [2- (dimethylamino) ethyl] acrylamide and methacrylamide, N- [3- (dimethylamino) -2-hydroxypropyl] methacrylamide or mono-olefinic derivatives of heterocyclic nitrogen4

No.336891 containing monomers such as "N-vinyl-pyrrole, N-vinyl-succinimide, l-vinyl-2-pyrrolidone, 1-vinyl-imidazole, Irvinyl-indole, 2-vinyl-imidazole, 4 (5) - Vinyl-imidazole, 2-vinyl-1-methyl-imidazole, 5-vinyl-pyrazoline, 3-methyl-5-isopropenyl-pyrazole, 5-methylene-hydantoin, 3-vinyl-2-oxazolidone, 3-methaerylyl-2 oxazolidone, 3-metbacrylyl-5-methyl-2-oxazolidone, 3-vinyl-5-methyl-2-oxazolidone, 2- and 4-vinylpyridine, 5-vinyl-5-methylpyridine, 2-vinylpyridine -l-oxide, 3-isopropenylpyridine, 2- and 4-vinyl-piperidine, 2- and 4-vinyl-quinoline, 2,4-dimethyl-6-vinyl-s-triazine, 4-acrylyl-morpholine.

These monomers may be used alone or in combination with each other or with other suitable vinyl monomers which may also be hydrophobic. The proportion of these hydrophobic monomers should not exceed 60% of the total composition, preferably 40%.

Suitable hydrophobic monomers are, for example, water-insoluble olefinic monomers such as alkyl acrylates or methacrylates in which alkyl has from 1 to 18 carbon atoms, for example methyl and ethyl methacrylate or acrylate; vinyl esters derived from alkanecarboxylic acids having 1 to 5 C atoms, for example vinyl acetate, acrylonitrile, styrene and vinyl alkyl ethers, in which the alkyl group of the ether chain has 1 to 5 C atoms, for example (methyl, ethyl, propyl, butyl or amyl -) vinyl ether.

Water-soluble monomers requiring a comonomer for polymerization are maleates, fumarates and vinyl ethers; the following monomer combinations can be used, for example, di- (hydroxyalkyl) maleates such as di (2-hydroxyethyl) maleate and ethoxylated hydroxyalkyl maleates, hydroxyalkyl monomaleates such as 2-hydroxyethyl monomaleate and hydroxylated hydroxyalkyl monomaleates with vinyl ethers, vinyl esters, styrene or in general monomers which readily copolymerize with maleates or fumarates; Hydroxyalkyl vinyl ethers, such as 2-hydroxyethyl vinyl ether, 4-hydroxybutyl-vinyl ether with maleates, fumarates or in general all monomers which readily copolymerize with vinyl ethers.

Particularly valuable as water-soluble monomers are hydroxyalkyl acrylates and methacrylates, such as, for example, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropylmetbacrylate, 2,3-dihydraxypropyl methaerylate, N-vinyl pyrrolidone, acrylic acid, methacrylic acid and a 25 tert. Amino-methacrylimide, eg, trimethylamino-methacrylimide, as described in U.S. Patent No. 3,627,802.

The most preferred monomers are 2-hydroxyethyl methacrylate and N-vinylpyrrolidone.

In the di-olefinic non-hydrophilic macromers B, the olefinic moiety is preferably an acyl residue of a lower α, β-mono-unsaturated aliphatic monocarboxylic or dicarboxylic acid or a vinyloxy residue. These best are interconnected by a macromolecular, non-hydrophilic chain with repeated ester, amide or urethane groups, but especially ether groups. The molecular weight of the chain can vary from about 400 to about 8,000, but preferably between 600 and 5,000, and most preferably between 1,500 and 3,000. Accordingly, the component B corresponds to the formulas

R "(B,)

HC = CXYR₁ -YXC = CH or

HC-CO

CO-CH (B₂) ;No₄-n:

HC - CO

CO-CH wherein R * is a polycondensate chain having a molecular weight of from about 200 to about 8,000, containing hydrocarbon radicals attached to ether, ester, amide, urethane or urea radicals, R_G is hydrogen, methyl or - CH₂ - COOR₄in which R₄ Is hydrogen or an alkyl group having up to 10 C-Ato40 men, R is hydrogen or COOR, with the proviso that at least one of the radicals R and R_G Is hydrogen, X is Qxo, - COO - or - CONR_s Where R_G Is hydrogen or alkyl of up to 5 carbon atoms and Y is a direct bond or the radical R - Z, - CO - NH - R "- NH - CO - Z -, where R,. is bonded to X and is a branched or straight-chain alkylene radical having up to 7 C atoms, Z₁and Z_G is Qxo or - NR_G, and R? is the divalent radical of an aliphatic or aromatic diiso-cyanate with the proviso that when X is Qxo, Y is not a direct bond and R and R are hydrogen.

In the compounds of the formulas (Bp and (B₂In particular, R 1 represents a polypropylene oxide or a polytetramethylene oxide chain, but it may also mean a chain derived from dicarboxylic acids, diols, diamines or diisocyanates obtained by known polycondensation processes. The 50 terminal residues of the compounds of the formula (Bp correspond to the definitions of R₂ and R_G and if X - COO or - CONR_G means, the acyl radical is derived from the acrylic or methacrylic acid or

No. 3,369,891 to the monoacyl radicals of maleic, fumaric or itaconic acid or of monoalkyl esters of these acids with straight- or branched-chain alkanoies having 1 to 10 C atoms, such as methanol, ethanol, butanol, diisobutyl alcohol or decanol, or when X is oxygen , with the vinyloxy group of vinyl ethers. Compounds of formula (B) wherein Y is a direct bond are diesters of macromolecular diols wherein two

Hydroxy groups to the polycondensate chain R_t are bound in opposite terminal or near-terminal positions with α, β-unsaturated acids. Such diesters can be prepared from the cited macromolecular diols by known acylation techniques using reactive functional derivatives of suitable acids, eg, acrylic or methacrylic acid chloride, or monoalkyl esters of maleic, fumaric, or itaconic acids. Compounds of the formula (Bp with the amide group X are diamides obtained from macromolecular diamines by known acylation processes, for example by using the abovementioned acid chlorides or anhydrides The macromolecular diamines are prepared, for example, from the corresponding double molar amount of macromolecular diols of alkyleneimine, eg propyleneimine.

The macromolecular bis-maleamic acids are obtained according to the above-described reaction by using maleic anhydride as acylating agent for macromolecular diamines under heating or reaction with dehydrating agents for the preparation of macromolecular bismaleimido compounds of the formula (B). In these compounds, R can be, for example, one of the macromolecular polycondensates known as constituents of the compounds of the formula (B).

By the definition of formula (Bp, Yferner may be a bivalent radical -R-Z.sup.-CONH.sup.R.sup.NH-CO-Z_i mean. Therein is R_O For example, methylene, propylene, trimethylene, tetramethylene, pentamethylene, neopentylene 0 (2,2-dimethyltrimethylene), 2-hydroxytrimethylene, l, l-dimethyl-2- (l-oxo-ethyl) -trimethylene or l- (Dimethylenaminomethyl) -ethylene and in particular ethylene. The divalent radical R? is derived from an organic diisocyanate and is an aliphatic radical such as alkylene, eg Ethylene, tetramethylene, hexamethylene, 2,2,4-trimethylhexamethylene, 2,4,4-trimethylhexamethylene, fumaroyldiethylene or 1-carboxy-25-pentamethylene; a cycloaliphatic radical, eg 1,4-cyclohexylene or 2-methyl-1,4-cyclohexylene; an aromatic radical such as m-phenylene, p-phenylene, 2-methyl-m-phenylene, 1,2-, 1,3-, 1,5-, 1,6-, 1,7-, 1,8- , 2,3- and 2, 7-naphthylene, 4-chloro-l, 2- and 4-chloro-l, 8-naphthylene, l-methyl-2,4-, l-methyl-2, 7-, 4 -Methyl-l, 2-, 6-methyl-l, 3- and 7-methyl-l, 3-naphthylene, 1,8-dinitro-2, 7-naphthylene, 4,4'-diphenylene, 3,3 ' Dichloro-4,4'-diphenylene, 3,3'-dimethoxy-4,4'-diphenylene, 2,2'-dimethyl and 3,3¹ Dimethyl-4,4'-diphenylene, 2,2'-dichloro-5,5'-dimethoxy-4,4'-diphenylene, methylene-di-p-phenylene, methylene-bis- (3-chlorophenylene), ethylenedi -p-phenylene or hydroxydiphenylene.

If in the part of the formula (Bp the symbol Y is not a direct bond, then R_ß always be connected toX. They are therefore compounds of the formula (Bp in which Y denotes the bivalent radical mentioned,

Bis-vinyl ether, when X is oxygen, or bis-acrylate, bis-methacrylate, bis-maleate, Bis-35-fumarate and bis-itaconate, when X is -COO- or -CONR.

The more preferred divinyl macromers (B) consist of polytetramethylene oxide glycols of molecular weight from about 1000 to about 4000, end-saturated with 2,4-toluene diisocyanate and reacted with 2 moles of a 2-hydroxyalkyl acrylate or methacrylate. Particularly valuable is the macromer of polytetramethylene oxide glycol of molecular weight from about 1500 to about 3000, fully saturated with

2,4-toluene diisocyanate and reacted with about 2 moles of 2-hydroxyethyl methacrylate.

The novel hydrophilic copolymers of this invention are prepared by free radical copolymerization, either in solution or in bulk, of water-soluble mono-olefinic monomers As or a mixture of at least 30% water-soluble monomers Ai with 10 to 70% macromers of the formula (B_JThe polymerization is advantageously carried out with a free radical catalyst at temperatures ranging from about 40 ° C to about 150 ° C, preferably between about 50 ° C and about 100 ° C carried out. The presence of a therapeutically or otherwise biologically active substance during the polymerization may require a limitation of the polymerization temperature in view of the heat stability of the substance.

A preferred laboratory manufacturing process for the hydrogel article comprises dissolving the drug in the monomeric monomer solution prior to polymerization, wherein the desired drug concentration is selected with the macromer monomer ratio together to give the hydrogel the desired mechanical and water absorption properties, mixing together of about

From 0.02% to about 1% (by weight) of a suitable free radical catalyst and polymerizing the mixture at, for example, 80 ° C for about 2 hours in a closed mold to give the hydrogel as a flat film, containing the drug in quasi-solid solution. This film is then exposed to a temperature of about 100 ° C for about 12 hours in a high vacuum to remove residues of monomers and catalyst decomposition products.

A preferred laboratory process for making the hydrogel in cylindrical form is to use a flexible polyethylene tube with the preferred mixture of macromer, monomer, drug no.336891

- 6 medium and catalyst is filled and the mixture is allowed to react for about 2 h at 80 ° C. The hydrogel article so made is freed from the ear by longitudinal slitting and stripping thereof.

Another preferred method for making the hydrogel in the form of small spheres or beads is that the preferred mixture of macromer, monomer, drug, and catalyst is at about 90 ° C in a viscous medium that does not act as a solvent for a component of the hydrogel slurry. is stirred at high speed. Examples of suitable media for bead polymerization are silicone oils, polyfluorinated oils and the like. called, for example Mineral oil distillates and saturated aqueous salt solutions.

Still another preferred method for producing the hydrogel in the form of a foamed article is by adding a gas generating agent (propellant), such as sodium bicarbonate, to the pre-drawn mixture and polymerizing it at about 80 C in a mold for about 1 hour , The resulting closed-cell foam is particularly suitable for rapid water absorption and drug release.

Compounds of formula (B) in which Y is - R - Z - CONHR - NH - CO - Z - are obtained in 1 6 17 2 of a two - step reaction by first preparing macromolecular diols or diamines, ie Compounds containing two hydroxy or amino groups in opposite terminal or near-terminal position bonded to the polycondensate R *, are reacted with at least twice the amount of an aliphatic, cyeloaliphatic or aromatic Diisoeyanats, wherein the diisocyanate from the radical R_? to which two isocyanate groups are bonded, and in the second reaction step the macromolecular diisocyanates thus obtained are reacted with a compound of the formula * 3 * 2 <^C>

HC = C-X-R-ZH 6 1 where R_2> R₃, X, R₆ and Ζ_χ the above (for B_t) given meaning, implemented.

When X is oxygen, (C) is a vinyl ether with active hydrogen, eg, a hydroxyalkyl vinyl ether or an aminoalkyl vinyl ether; when X is -COO- or CONR, (C) is an acrylate, methyl acrylate, maleate, fumarate, itaconate or the corresponding active hydrogen amide in the alkyl group. The macromolecular diol or diamine is preferably used in slight excess, that is, the ratio of isocyano groups to hydroxy or amino groups in the first reaction step of the macromolecular synthesis should be at least 1: 1, but preferably at least 1: 1.05 or lower. When the compound (C) used in the second reaction step of macromer synthesis is identical to the hydrophilic monomer As, a large excess of this compound can be used so that the resulting solution of the macromer (Bp dissolved or dispersed in the monomer (A.), Directly for the preparation of the final product, the hydrophilic copolymer can be used.

The preparation of macromer (B) is advantageously carried out at temperatures ranging between about room temperature and about 80 ° C. The temperature used is preferably not higher than 35-40 ° C, and most preferably in the range of 30-45 ° C. The conversion of the isocyanuro group is by means of

Infrared spectroscopy or titration followed.

Another method of preparing the macromer is to react a hydroxyl-terminated prepolymer, eg polybutylene or polypropylene oxide, with acryloyl chloride, methacryloyl chloride or maleic anhydride to form a macromer without urethane linkers, such as a macromer of the formula (Bp or (Bp where Y is a direct bond.

The free radical copolymerization is initiated by means of a catalyst capable of generating free peroxy or alkyl radicals in sufficiently high concentration to effect polymerization of the employed vinyl monomer at the synthesis temperature.

Examples of suitable catalysts are diisopropyl peroxydicarbonate, tert. Butyl peroctoate, benzoyl peroxide, decanoyl peroxide, lauroyl peroxide, succinic peroxide, methyl ethyl ketone peroxide, tert. Butyl peroxyacetate and azoisobutyronitrile. When the polymerization is carried out in water, water-soluble peroxy compounds such as sodium, potassium or ammonium persulfate, as well as free-radical generating redox systems such as persulfate-bisulfite combinations can be used. The catalyst is advantageously used in an amount of about 0.02 to 1% by weight of the reaction mixture. 50 other free-radical generating systems can also be used, such as gamma rays, electron beams and UV radiation.

The reaction is preferably carried out in an inert or oxygen-free atmosphere, if working with open molds. It is known that oxygen inhibits the polymerization and prolongs the polymerization times until the reaction is complete. When working with closed molds to form the hydrogel article, low oxygen inert material molds must be replaced by No. 3636891

- 7 permeability and good detachability. Examples of suitable mold material are, for example, silicone rubber and polyethylene. Glassy and metallic molds can be used if a suitable mold releasing agent is used.

The incorporation of the drug into the hydrogel article is accomplished either by dissolving or dispersing in the macromer solution, the monomer solution or the mixture of both prior to the addition of the free radical catalyst, or by diffusion of the drug into the article obtained after polymerization. If the drug is not attacked by free radicals, it is advantageous to dissolve or disperse it in the macromer solution, monomer solution or mixture of both before polymerization. If the drug is attacked by free radicals, it should be incorporated after polymerization into the finished article by diffusion from solution.

The hydrogel system consisting mainly of the hydrophobic macromeric segment (B) and the hydrophilic segment may be of quite varied composition, and accordingly, the degree of hydrophilicity and mechanical strength may be balanced against each other so that there is a wide variety of applications. such as drug delivery systems, insecticides, herbicides, etc., semi-permeable reverse osmosis membranes, Body implants and wound dressings.

In addition to medicaments, the copolymers according to the invention may also contain fragrances or flavorings such as orange oil, citral, coffee, tea, lemon oil, synthetic lime-lemon flavor, strawberry flavor, vanilla, diacetyl, anise, lilac scent, spruce fragrance, peppermint oil, orchid oil or essence, anethole, Ethyl propionate, ethyl acetate, acetaldehyde, menthol and garden mint, as well as pesticides included bactericides, fungicides,

Insecticides and nematocides are incorporated.

Other examples of the mentioned biologically active additives are mentioned in US Pat. No. 3,660,563 (columns 3 to 7).

The novel hydrogels, especially the polyurethanes containing macromer component, due to their superior physical properties in the dry and wet state form a cross between classical hydrogel and polyurethane and are particularly valuable as biomedical plastics with non-thrombogenic properties. They are therefore excellently suited for use as artificial skin in the treatment of burns, for the construction of artificial organs or as covering layers for the same. They can also be used as surgical sutures.

The composition of the hydrogels may vary from 30 to 90% monomer (A) and from 10 to 70% Macroemmer (B), with a corresponding degree of swelling of about 10 to 250%. The preferred compositions contain about 15 to 50% macromer (B) and about 50 to 85% monomer (A), and their degree of swelling ranges between 15 and 120%.

Experimental part

After the preparation of the gel a 3 g heavy piece is cut off, weighed and in one

Bottle with about 50 ml of water stored at room temperature. After 96 hours, the swollen pattern is taken out, freed of excess surface water with filter paper and weighed again to determine the degree of swelling (DS). From the remaining hydrogel film six test strips are punched, of which three are allowed to swell in water until the Gleiehgewichtswassergehalt is reached. Tensile strength and elongation of the dry and wet samples are determined in an Instron testing machine according to ASM test method D-638 using a Type IV test strip.

The rate of release of a drug contained in a hydrogel is determined by continuous measurement of the characteristic UV absorbance of a stirred amount of water containing a hydrogel disc 16 mm in diameter and 0.8 to 1.0 mm in thickness.

", Wet pattern weight - weight of the dry pattern

Degree of swelling DS = weight of the dry sample *¹⁰⁰

In the following examples, the term isocyanate-terminated polytetramethylene oxide (isocyanate-end-saturated polytetramethylene oxide) means a polytetramethylene oxide chain reacted at both ends with 2,4-toluene diisocyanate.

The first seven examples show the effect of varying amounts of macromeric hydrophobic crosslinking agent on the physical properties of polyhydroxyethylmethacrylate gels and theirs

Production.

A: 2-hydroxyethyl methacrylate

B: Polytetramethylene oxide reacted terminally with isocyanate + 2-hydroxyethyl methacrylate.

Example 1: 20 g of 1500 molecular weight polytetramethylene oxide end-capped with isocyanate are dissolved in 18 g of 2-hydroxyethyl methacrylate and placed at room temperature for 72 hours at room temperature. After 72 hours, the disappearance of total isocyanate is confirmed by detecting the absence of the characteristic infrared band of isocyanate at 2270 cm^-1 in the infrared spectrum. This mixture will

No.336891 then injected ge after addition of 0.08 g of diisopropyl percarbonate in a mold for films of 1 mm thickness and held for 2 h in a rotary kiln at 60 ° C. The obtained solid, transparent film is placed in water for 2 days and then dried in vacuo at 80 ° C. Equilibrium water content, tensile strength and elongation in dry and wet conditions are measured.

Example 2: The procedure of Example 1 is repeated except that 2.0 grams of 3000 molecular weight polytetramethylene oxide reacted terminally with isocyanate. A tough, transparent film is obtained which, after soaking in water for 2 days and then drying in vacuo at 80 ° C., is tested as described in Example 1,

Example 3: The process according to Example is carried out with 5.0 g of polytetramethylene oxide (molecular weight 1500) and 15.0 g of 2-hydroxyethyl methacrylate. The product obtained is a tough, transparent film, which is treated as described in Example 1.

Example 4: The procedure of Example 1 is repeated, but the composition of the

Reaction mixture modified in 10.0 g of polytetramethylene oxide (molecular weight 1500) and 10.0 g of 2-Hydroxyätiiylmethacrylat »A tough, transparent film is obtained and treated as described in Example 1 be15.

Example 5: The procedure according to Example 2 is repeated with a different composition of the reaction mixture, by reacting 5.0 g of polytetramethylene oxide (molecular weight 3000) and 15.0 g of 2-hydroxyethyl methacrylate. A tough, transparent film is obtained and treated as in Example 1.

Example 6: The procedure according to Example 2 is repeated with the mixture of 10.0 g of polytetramethylene oxide (molecular weight 3000) and 10.0 g of 2-hydroxyethyl methacrylate. A tough, transparent film is obtained, treated and tested as in Example 1.

Example 7: For control, a conventional poly (2-hydroxyethyl) methacrylate gel is prepared, starting from 1.2% ethylene glycol dimethacrylate as crosslinking agent; Otherwise, the same procedure is used as for the previously described gels. A hard, brittle, transparent sheet is obtained which is treated and tested the same way as described above. Table I shows a decreasing degree of swelling with increasing amount of hydrophobic macromer (B). The tensile strength in the dry state of the products according to Example 1 to 6 is higher than in the conventional poly (2-hydroxyethyl) methacrylate according to Example 7.The tensile strength in the wet state and the elongation in the dry and wet state increase with increasing amount of (B ).

Table I

<td rowspan="2">example</td><td colspan="2">Macromeric (B)% polytetramethylene</td><td rowspan="2">Monomer (A)% s 2-hydroxyethyl methacrylate</td><td rowspan="2">*** DS</td><td rowspan="2">tensile strenght dry</td><td rowspan="2">strain damp</td>

<td>oxide</td><td></td>

<td>1</td><td>* MW 1500</td><td>11.6</td><td>88.4</td><td>52</td><td>4560/41</td><td>185/99</td>

<td>2</td><td>MW 3000</td><td>10.8</td><td>89.2</td><td>42</td><td>5343/39</td><td>150/108</td>

<td>3</td><td>MW 1500</td><td>29</td><td>71</td><td>22</td><td>4760/89</td><td>409/113</td>

<td>4</td><td>MW 1500</td><td>58</td><td>42</td><td>12</td><td>4123/144</td><td>1055/150</td>

<td>5</td><td>MW 3000</td><td>27</td><td>73</td><td>30</td><td>4453/120</td><td>258/95</td>

<td>6</td><td>MW 3000</td><td>54</td><td>46</td><td>20</td><td>3167/246</td><td>557/214</td>

<td>7</td><td>-</td><td></td><td>98.5</td><td>45</td><td>2320/15</td><td>69/83</td>

* MW = molecular weight A = water-soluble monomer *** DS = degree of clogging

The following examples demonstrate the utility of N-vinylpyrrolidone as a hydrophilic monomer (A), as well as the use of hydrophobic comonomers to adjust the equilibrium water content.

Examples 8 to 12: 30 g of a polytetramethylene oxide, end-saturated with isocyanate, of molecular weight 3000 are dissolved in 40 g of N-vinylpyrrolidone and 10 g of 2-hydroxyethyl methacrylate; After 72 hours, all free iso-adyanate has disappeared. The solution is then split into four equal parts and 5 g of the following monomer are added:

Example 8: N-vinylpyrrolidone

Example 9: Ethyl Acrylate 40 Example 10: Dimethyl Maleate

Example 11: Vinyl acetate

No.33 6891

Example 12: Ethyl Aerylate.

For all five mixtures 0.1 g tert. Butyl peroctoate was added and the solutions poured into a mold for films of 1 mm thickness. It is reacted at 80 ° C for 2 h, taken out of the mold and kept at 100 ° C for 15 h in a vacuum of 0.25 mm. The films thus produced are clear and tough and their degree of swelling was determined as follows (see Table Π).

Table II

<td rowspan="3">example</td><td colspan="3" rowspan="2">Macromeres (B)%</td><td colspan="4">Monomeric system (A)</td><td rowspan="3">Quel- lungs- Degree</td>

<td>%</td><td>+</td><td colspan="2"></td>

<td>polytetramethylene methylene oxide MW 3000</td><td>+</td><td>2-hydroxy ätbyl- meth acrylate</td><td>N-vinyl pyrrolidone</td><td>+</td><td>2-hydroxy ethyl- meth acrylate</td><td>** % (Ap comonomers</td>

<td>8th</td><td></td><td>32.4</td><td></td><td>60</td><td>+</td><td>7.6</td><td>-</td><td>101</td>

<td>9</td><td></td><td>32.4</td><td></td><td>40</td><td>+</td><td>7.6</td><td>Ethyl acrylate 20</td><td>75</td>

<td>10</td><td></td><td>32.4</td><td></td><td>40</td><td>+</td><td>7.6</td><td>Dimethyl maleate 20</td><td>78</td>

<td>11</td><td></td><td>32.4</td><td></td><td>40</td><td>+</td><td>7.6</td><td>Vinyl acetate 20</td><td>91</td>

<td>12</td><td></td><td>22, 6</td><td></td><td>29</td><td>+</td><td>5.4</td><td>Ethyl acrylate 43</td><td>42</td>

* A = hydrophilic monomer ** A | = water-soluble mono-olefinic monomer

In the following two examples, the Macromere (B) is a bis-vinyl ether (Example 12) and a bis-maleate (Example 14).

Example 13: Following the procedure described in Examples 8 to 12, 30 g of isocyanate 10 end-saturated polytetramethylene oxide (molecular weight 3000) and 10 g of 4-hydroxybutyl vinyl ether are reacted in 30 g of N-vinylpyrrolidone until all the free isocyanate has disappeared. To the mixture are added thereto 30 g of ethyl acrylate, and 0.4 g of tert. Peroctoate. The mixture is placed in film molds and after 2 hours at 80 ° C the crosslinked films are removed from the mold and held for 16 hours in a vacuum oven (0.25 mm Hg) at 100 ° C. The specimen is a tough, clear leaf whose degree of quenching has been determined (see Table III).

Example 14: Following the procedure described in Examples 8 to 11, 40 g of isocyanate end-saturated polytetramethylene oxide (molecular weight 3000) and 10 g of 3-hydroxypropyl-butyl maleate are reacted in 50 g of N-vinylpyrrolidone until all the free isocyanate has been removed. 0.4 g of tert. Butyl peroctate is added. The mixture is placed in film molds and exposed for 2h 20 at a temperature of 80 ° C. The crosslinked film is removed from the mold and held at 100 G for 16 hours (0.25 mm Hg). The pattern is a tough, clear sheet whose degree of swelling has been determined (see Table HI).

Nr.336891

Table III

<td rowspan="2">examples game</td><td colspan="2">Macromeres (B)%</td><td colspan="3">Monomeric system (A.)</td><td rowspan="2">*** DS</td>

<td>poly- tetra me- thylen- oxide</td><td>end stän- ended mono- (- meres</td><td>% A / 4-hydroxy- bulyl- N-vinyl-vinyl pyrrolidone + ether</td><td>4-hydroxypropylbuiyl + maleate</td><td>". ** % Aj comonomers</td>

<td>13</td><td>32.4</td><td>4-hy- droxy- butyl vinyl- ether</td><td>30 + 7,6</td><td></td><td>30</td><td>72</td>

<td>14</td><td>43.1</td><td>3-hybrid droxy- propyl bulyl- maleate</td><td>50 + -</td><td>6.9</td><td></td><td>89</td>

A_s = water-soluble monomer ** A · = water-soluble mono-olefinic monomer sfsstczic J * D = degree of swelling b

In the following examples, the macromeric crosslinker contains linear polyesters and polypropylene oxide chains.

Examples 15 to 17: An isocyanate-end-saturated polyester of molecular weight 425 5 is mixed with 2-hydroxyethyl methacrylate in the following proportions:

Example 15: 15 g of polyester diisocyanate + 85 g of 2-hydroxyethyl methacrylate

Example 16: 25 g of polyester diisocyanate + 75 g of 2-hydroxyethyl methacrylate

Example 17: 40 g of polyester diisocyanate + 60 g of 2-hydroxyethyl methacrylate.

The mixtures are allowed to stand for 72 g at room temperature; After this time, all 10 isocyanate has been implemented. 0.4 g tert. Butyl peroctoate is added to each of the batches and then added to film molds of 1 mm thickness. The samples are heated to 80 ° C for 2 hours, taken out of the molds and exposed to a temperature of 100¾ for 16 hours in a vacuum oven (0.25 mm Hg). The translucent films are tough and flexible; Their degree of swelling is shown in Table IV.

Table IV

<td rowspan="2">example</td><td colspan="2">% Macromeres (B)</td><td>Monomer (A) %</td><td rowspan="2">swelling</td>

<td>Polyester (E-410) +</td><td>2-hydroxyethyl methacrylate</td><td>2-hydroxyethyl methaerylat</td>

<td>15</td><td>23.4</td><td></td><td>76, 6</td><td>30</td>

<td>16</td><td>39</td><td></td><td>61</td><td>21</td>

<td>17</td><td>62</td><td></td><td>38</td><td>21</td>

Examples 18-19: A bis-maleimide type macromer (B) of molecular weight about 2200 (polypropylene oxide-bis-maleimide) obtained by reacting 2 moles of maleic anhydride with 1 mole of polypropylene oxide end-saturated with primary amino groups is dissolved in 2-hydroxyethyl methacrylate in two proportions :

Example 18: 20% polypropylene oxide-bis-maleimide (80% 2-hydroxyethyl methacrylate)

Example 19: 35% polypropylene oxide-bis-maleimide (65% 2-hydroxyethylmethacrylate)

0.1% tert. Butyl peroctoate are added and the solutions reacted in film molds at 80 ° C for 2 h; the films are taken out and kept in a vacuum oven (0.25 mm Hg) at 100 ° C for 16 h; they are then tough and supple; their degree of swelling is shown in Table V11

No. 3636891.

Table V

<td rowspan="2">example</td><td>Macromeres (B) %</td><td>Monomer (A) %</td><td rowspan="2">swelling</td>

<td>Polypropylene oxide bis maleimide</td><td>2-hydroxyethyl methacrylate</td>

<td>18</td><td>20</td><td>80</td><td>44</td>

<td>19</td><td>35</td><td>65</td><td>33</td>

Example 20: 53.0 g of polypropylene oxyd-bis-maleimide according to Example 18 and 19 are dissolved in 47.0 g of N-vinylpyrrolidone; after addition of 0.4 g tert. Butyl peroctoate, the mixture is poured into molds and reacted as described in Example 18. A tough, slightly brown colored gel is obtained which absorbs 46.0% of its weight in water (DS = 46.0).

Example 21: 59.8 g of polypropyleneaxydib-maleimide according to Examples 18 and 19 are dissolved in 27.1 g of N-vinylpyrrolidone and 13.0 g of ethyl acrylate; after addition of 0.4 g tert. Butyl peroctoate, the mixture is filled into molds and as described in Example 18, implemented. The gel forms a tough, slightly yellowish film that absorbs 26.5% of its weight in water (DS = 26.5).

Example 22: Example 21 is repeated but with amounts of 3.10 g of N-vinylpyrrolidone and 26.4 g of ethyl acrylate. The product obtained is a tough, colorless gel which absorbs 23.0% of its weight in water (DS = 23.0).

Example 23: Example 21 is repeated but with amounts of 27.1 g of N-vinylpyrrolidone and 43.5 g of 15% ethyl acrylate. The resulting gel is tough and colorless; it absorbs 15.8% of its weight in water (DS =

15.8).

Example 24: To 150 g of N-vinylpyrrolidone are added 200 g of isocyanate-end-saturated polytetramethylene oxide (molecular weight 3000) and 50 g of 2-hydroxyethyl methacrylate. The solution is stirred at 25 ° C in an inert atmosphere for 1 week. After this time, the completion of the reaction 20 between diisocyanate and 2-hydroxyethyl methacrylate is confirmed by detecting the disappearance of the NCO band in the infrared spectrum of the final product. This is stored and serves as starting material for the preparation processes according to Examples 25 to 37.

Example 25: 20, Og of the starting material according to Example 24 are tert with (sufficient). Butyl peroctoate catalyst mixed (to bring the final concentration of catalyst to 0.4 wt .-%). The mixture is placed in a closed mold to produce a film of 1 mm thickness. The mold is placed in a hot air oven to complete polymerization at 80 ° C for 2 hours. The polymer film is removed from the mold and for 18 h at a temperature of 80 ° C at a vacuum of

0.1 mm exposed. The product is a clear, tough film whose degree of swelling is determined.

Example 2 6: The procedure of Example 25 is repeated except that 1.0 g of 2-hydroxy-30-ethylmethacrylate and 4 g of N-vinylpyrrolidone are added prior to the addition of the peroxide.

Example 27: The procedure of Example 25 is repeated except that 2.0 g of 2-hydroxyethyl methacrylate and 3.0 g of N-vinylpyrrolidone are added prior to the peroxide addition.

Example 28: The procedure of Example 25 is repeated, except that 4.0 g of 2-hydroxyethyl methacrylate and 1.0 g of N-vinylpyrrolidone are added to the starting material (according to

Example 32) are added.

Example 29: The procedure of Example 25 is repeated except that 5.0 g of 2-hydroxyethyl methacrylate is added prior to the peroxide addition.

Example 30: The procedure of Example 25 is repeated except that 3.0 g of N-vinylpyrrolidone and 27.0 g of 2-hydroxyethyl methacrylate are added before the peroxide is added.

Example 31: The procedure of Example 25 is repeated except that 24.0 g of 2-hydroxyethyl methacrylate and 6.0 g of N-vinylpyrrolidone are added before the peroxide addition.

Example 32: The procedure of Example 25 is repeated except that each 15.0 g of 2-hydroxyethyl methacrylate and N-vinylpyrrolidone are added before the peroxide addition.

Example 33: The procedure of Example 25 is repeated except that 5.0 g of N-vinyl-4-pyrrolidone and 25.0 g of 2-hydroxyethyl methacrylate are added before the peroxide addition.

Example 34: The procedure of Example 25 is repeated except that 3.53 g of ethyl acrylate are added before the peroxide addition.

Example 35: The procedure of Example 25 is repeated except that 6.67 grams of ethyl acrylate are added prior to the peroxide addition.

Example 36: The procedure of Example 25 is repeated except that 10.8 g of ethyl 12

No. 366,891 acrylate before adding peroxide.

Example 37: The procedure of Example 25 is repeated, except that 20.0 g of ethyl acrylate is added before the peroxide addition.

The composition and degree of swelling of the gels according to Examples 25 to 37 are summarized in Table VI.

Table VI

<td rowspan="4">example</td><td>Macromeres (B)%</td><td colspan="3" rowspan="2">Monomer (A)%</td><td rowspan="4">swelling Degree</td>

<td rowspan="3">Polytetramethylene-2-hydroxy oxide ethyl- MW 3000 + acrylate</td>

<td colspan="2">A *^As</td><td rowspan="2">Λ ** A 1 *** EA</td>

<td>N-vinylpyrrolidone +</td><td>2-hydroxyethyl methacrylate</td>

<td>7</td><td>-</td><td>-</td><td>98.5</td><td>-</td><td>52</td>

<td>25</td><td>54</td><td>37.5</td><td>8.5</td><td>-</td><td>26</td>

<td>26</td><td>43.2</td><td>46</td><td>11.8</td><td>-</td><td>71</td>

<td>27</td><td>43.2</td><td>42</td><td>14.8</td><td>-</td><td>60</td>

<td>28</td><td>43.2</td><td>34</td><td>22.8</td><td>-</td><td>50</td>

<td>29</td><td>43.2</td><td>30</td><td>26.8</td><td>-</td><td>41</td>

<td>30</td><td>21.6</td><td>69</td><td>9.4</td><td>-</td><td>173</td>

<td>31</td><td>21.6</td><td>63</td><td>15.4</td><td>-</td><td>153rd</td>

<td>32</td><td>21.6</td><td>45</td><td>33.4</td><td>-</td><td>93</td>

<td>33</td><td>21.6</td><td>25</td><td>53.4</td><td>-</td><td>55</td>

<td>34</td><td>39.1</td><td>31.9</td><td>7.2</td><td>15</td><td>82</td>

<td>35</td><td>34.5</td><td>28.1</td><td>6.4</td><td>25</td><td>71</td>

<td>36</td><td>22.4</td><td>24.4</td><td>5.5</td><td>35</td><td>56</td>

<td>37</td><td>23</td><td>18.8</td><td>4.2</td><td>50</td><td>28</td>

* A = water-soluble monomer g

** A. = water-soluble mono-olefinic monomer *** EA = acyl butylate

Example 38: A) Preparation of the macromeric matrix:

2000 Parts (1 mole) of 2000 molecular weight polytetramethylene oxide are melted, poured into a three necked flask and heated to 80 ° C under vacuum for 1 hour to remove residual moisture. The vacuum is released by introducing dried nitrogen gas and the contents of the flask are cooled down to 40 ° C. To this are added 444.6 parts (2 moles) of isophorone diisocyanate and 1 g of triethylamine, the temperature being raised to 80 ° C. After the Isocyananaigehalt has fallen after 5häufung approximately 3.5% (the determination was carried out by titration), the Raktionsgemisch is cooled to 40 C and then with 1630 parts of 2-HydroxyäthyImethacrylat and 0.24 g dibutyltin dilaurate sets ver.Man is the Reaktionsgemiseh with stirring Cool to room temperature in a steamer atmosphere until the residual isocyanate disappears completely.

B) Preparation of Crosslinked, Hydrophilic Polymers:

The starting macromeric compound prepared according to A) is used to form monomer macromers

To obtain mixtures of the following composition by adding either more 2-hydroxyethyl methacrylate 20 or N-vinylpyrrolidone:

<td>Example 46</td><td>Macromere (%)</td><td>Composition 2-hydroxyethyl methacrylate (%)</td><td>N-vinylpyrrolidone (%)</td>

<td>a</td><td>68</td><td>32</td><td>-</td>

<td>b</td><td>45</td><td>55</td><td>-</td>

<td>c</td><td>34</td><td>66</td><td>-</td>

<td>d</td><td>11</td><td>89</td><td>-</td>

<td>e</td><td>22</td><td>53</td><td>25</td>

<td>f</td><td>22</td><td>33</td><td>45</td>

<td>G</td><td>22</td><td>15</td><td>63</td>

Nr.336891

To each monomer-macromeren mixture obtained are 0.2 parts tert. Butyl peroctoate was added, dissolved and the solutions obtained in injection molds (30 x 30 cm) injected from glass, which are lined with polyester films, using 1, 6 mm wide silicone tapes as spacers. The polymerization is carried out in a hot-air oven by heating at 80 ° C. for 3 hours and heating at 100 ° C. for 5 hours. The molds are taken out, cooled to room temperature and then characterized Hydrogelfolien characterized.

Swelling degree, tensile strength (wet and dry) and ductility (wet and dry) of the hydrogel obtained according to a) to g) are given in the following table:

<td rowspan="2">Example 38</td><td rowspan="2">Degree of swelling (%)</td><td colspan="2">tensile strenght</td><td colspan="2">Extensibility%</td>

<td>dry</td><td>wet</td><td>dry</td><td>wet</td>

<td>a</td><td>10</td><td>2720</td><td>1140</td><td>170</td><td>210</td>

<td>b</td><td>20</td><td>3460</td><td>490</td><td>130</td><td>160</td>

<td>c</td><td>27</td><td>4290</td><td>340</td><td>110</td><td>145</td>

<td>d</td><td>47</td><td>5910</td><td>120</td><td>50</td><td>120</td>

<td>e</td><td>61</td><td>5950</td><td>110</td><td>58</td><td>73</td>

<td>f</td><td>96</td><td>6620</td><td>85</td><td>67</td><td>60</td>

<td>G</td><td>138</td><td>7100</td><td>24</td><td>40</td><td>20</td>

Example 39: 125.0 g (0.13 mol) of polyoxypropylene, molecular weight 995, are poured into a 500 ml three-necked flask and dried for 1 hour at 80 ° C / 2 mm Hg. The vacuum is released by introducing dried nitrogen gas and the contents of the flask are cooled down to 40 ° C. To this are added 55.9 g (0.25 mol) of isophorone diisocyanate and 127 mg of triethylamine, the reaction temperature being raised to 80 ° C. After 18 h reaction time, the isocyanate content is 5.8% (theoretical value = 5.84% isocyanate). The reaction mixture is cooled to 40.degree. 172, 8 g (1.3 mol) of 2-hydroxyethyl methacrylate are added to 115.2 g of the reaction mixture obtained above and admixed with 9.6 mg of dibutyltin dilaurate [dibutyl-bis- (lauroyloxy) -tin]. The reaction mixture is kept at a temperature of 40 ° C until complete disappearance of the residual isocyanate.

Example 40: 150.0 g (0.074 mol) of polyoxypropylene, molecular weight 2015, are poured into a 500 ml three-necked flask and dried at 80 ° C / 2 mm Hg for 1 h. The vacuum is released by introducing dried nitrogen gas and the contents of the flask are cooled down to 40 ° C. To this are added 33.1 g (0.15 mol) of isophorone diisocyanate and 83 mg of 1,4-diazabicyclo [2.2.2] octane (1 mol%), the reaction temperature being raised to 80 ° C. After a reaction time of 16 hours, the isocyanate content is 3.44% (theoretical value = 3.42% isocyanate). The reaction mixture is cooled to 40.degree. 179.3 g (1.4 mol) of 2-hydroxyethyl methacrylate are added to 119.5 g of the reaction mixture obtained above and treated with 190 mg of dibutyltin dilaurate. The reaction mixture is kept at a temperature of 40 ° C until complete disappearance of the residual isocyanate.

Example 41: 143.9 g (0.50 mole) of polyoxypropylene, molecular weight 2878, are poured into a 500 ml three-necked flask and dried at 80 ° C / 2 mm Hg for 1 hour. The vacuum is released by introducing dried nitrogen gas and the contents of the flask are cooled to 40 ° C. To this are added 22.2 g (0.10 mol) of isophorone diisocyanate and 56 mg of 1,4-diazabicyclo [2,2,2] octane (1 mol%), the reaction temperature being raised to 80 ° C. After a reaction time of 12 hours, the isocyanate content is 2.44% (theoretical value = 2.53% isocyanate). The reaction mixture is cooled to 40.degree. 308.0 g (2.37 mol) of 2-hydroxyethyl methacrylate are added to 205.3 g of the reaction mixture obtained above and admixed with 35 17 mg of dibutyltin dilaurate [dibutyl-bis (lauroyloxy) -tin]. The reaction mixture is kept at a temperature of 40 ° C. until the residual isocyanate disappears completely.

Example 42: 145.9 g (0.074 mol) of a molten polyester diol, molecular weight 1965, are poured into a 500 ml three-necked flask and dried at 80 ° C / 2 mm Hg for 1 h. The vacuum is released by introducing dried nitrogen gas and the contents are cooled to 40 ° C. 40 33.0 g (0.15 mol) of isophorone diisocyanate and 83 mg of 1,4-diazabicyclo [2.2.2] octane are added thereto, and the temperature is raised to 80.degree. After a reaction time of 7 hours, the isocyanate content is 3.48% (theoretical value = 3.49 isocyanate). The reaction mixture is cooled to 40.degree. 222.0 g (1.7 mol) of 2-hydroxyethyl methacrylate are added to 148.0 g of the reaction mixture obtained above and treated with 12 mg of dibutyltin dilaurate. The reaction mixture is kept until the complete disappearance of the residual isocyanate at a Tem45 temperature of 40 ° C.

Example 43: To 50.0 g of each of the reaction mixtures (compounds) obtained in Examples 39 to 42, 0.1 g of tert. Butyl peroctoate added and dissolved with stirring. The resulting mixture is degassed at room temperature in a vacuum of 1 mm Hg until no rising bubbles

- 14 No.33 6891 more can be observed and then poured into a glass mold, which has been lined with Mylar polyester film and sealed with 1 mm wide silicone tape. The molds are heated in a hot air oven for 3 h at 80 ° C and then for 1 h at 100 ° C. The resulting films are stripped from the cooled molds and cut into samples for analysis and physical testing.

Degree of swelling (DS) and tensile strength for the hydrogels obtained according to Examples 39 to 42 are given in the following table:

<td rowspan="2">example</td><td rowspan="2">Degree of swelling%</td><td colspan="2">tensile strenght</td><td colspan="2">Extensibility%</td>

<td>dry</td><td>wet</td><td>dry</td><td>wet</td>

<td>39</td><td>20</td><td>3980</td><td>433</td><td>89</td><td>111</td>

<td>40</td><td>22</td><td>3750</td><td>280</td><td>112</td><td>180</td>

<td>41</td><td>29</td><td>3600</td><td>250</td><td>113</td><td>126</td>

<td>42</td><td>19</td><td>4600</td><td>656</td><td>131</td><td>191</td>