Hydrophilic polymers,articles and methods of making same

<td colspan="2"></td><td colspan="2">© class: 39 b, 14</td>

<td></td><td>AUSTRIAN PATENT OFFICE</td><td> ©</td><td>Int. Cl .: C 08 f 15/18</td>

<td> ©</td><td>OE PATENCY</td><td> ©</td><td>No. 312930</td>

<td> ©</td><td>Patentee:</td><td>NATIONAL PATENT DEVELOPMENT CORPORATION IN NEW YORK</td>

<td> ©</td><td>Object:</td><td>Process for the preparation of a hydrophilic, liquid casting syrup</td>

<td> © ©</td><td>Addition to Patent No. Excretion from:</td><td></td>

<td> ©@ ©</td><td>Registered on: exhibition priority:</td><td>25th July 1967, 6921/67</td>

<td> ©©©</td><td>Union Priority:</td><td>United States of America (US), July 26, 1966, 567856</td>

© Start of patent term: May 15, 1973 Longest possible duration:

© Issued on: 25 January 1974 © Inventor:

Dr. Thomas H. Shepherd at Hopewell and Dr. Francis E. Gould of Princeton (USA) © Dependence:

OE 312 930 © Pamphlets considered as delimiting from the state of the art:

DT-AS 1 083 057 DT-AS 1 217 063 - 2 -

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The invention relates to a process for the preparation of a hydrophilic liquid pourable syrup,

It is known to produce hydrophilic polymers, in particular crosslinked hydrophilic polymers, for example in the form of shaped body hydrogels in aqueous solution by copolymerization, wherein a predominant amount of a monoester of acrylic acid or metacrylic acid and a bifunctional alcohol containing a esterifiable hydroxyl group and at least one additional having hydrophilic functional group, in aqueous solution with a small amount of a diester of one of these acids and an alcohol having at least two esterifiable hydroxyl groups (see US Pat. Nos. 2,976,576 and 3,220,960).

It is also known that the shaped, hydrophilic polymers prepared in an aqueous system are industrially useful as carriers for medically active substances. The medically effective substances were dissolved in the aqueous component of the molded hydrogels, whereby a gradual release of the medically active substances can be achieved. However, the resulting solutions are difficult to handle and store and the medical agents are subject to air oxidation, degradation, decomposition or volatilization.

In the previously known processes, it has been necessary to prepare a solid or molded body of the hydrophilic polymer and thereafter to dissolve the medicinal agent, flavor, sweetener or dye in the aqueous components of such a shaped body.

Moreover, in the hitherto known procedures which use the known redox catalysts such as sodium bicarbonate and ammonium persulfate, potassium sulfate, sodium thiosulfate and ammonium persulfate or potassium sulfate, the completion of the polymerization reaction was carried out at temperatures above 0 ° C, and thereby the formation of a prepolymer, preferably in the form of a liquid casting syrup, dyed as such, pigmented, can be thickened and otherwise modified in shape and then hardened to produce solid or shaped articles such as rods, plates, tubes and other molded articles or a hard, friable foam.

In addition, only incomplete (namely up to about 95%) polymerized through in the process known hitherto and further such a polymer, the excessively large amounts of water (more than 30 wt .-%, even up to 80 wt .-%) when it was equilibrated in aqueous solutions.

The polymers obtainable from the producible pourable syrups according to the present invention are substantially completely (ie, about 99.5%) fully polymerized and incapable of absorbing more than about 30% by weight of water when equilibrated in aqueous solutions.

A process has now been found with which directly in an anhydrous system liquid pourable syrups can be prepared in prepolymerized form, which can be used for direct in situ polymerization into cast or molded bodies, films and coatings, and which with the usual foams, such as Sodium bicarbonate can be treated to obtain hard friable foams, which can be further brought directly into the swollen state or ground into powder.

The pourable syrups obtainable according to the invention are suitable for rapid production of hydrophilic polymerization products in powder form. The pouring syrups can be directly converted, which are especially useful as carriers for medically active substances, natural or synthetic flavorings, essences, fragrances, spices and the like. are suitable. The powders made from the pourable syrups obtainable according to the invention are compact in shape and have the necessary stability and shelf life to be used as carriers for medical substances and flavorings exposed to chemical reactions such as air oxidation, evaporation and degradation.

The hydrophilic liquid pourable syrups are prepared according to the invention by, in the solvent-free state, a water-soluble, polymerizable hydroxyalkyl monoester of an aj3-unsaturated carboxylic acid, eg acrylic or methacrylic acid, especially hydroxyethyl methacrylate, with a small amount of free radical vinyl polymerisation catalyst sufficient to polymerize a substantial amount of the monomer into a water-insoluble product, cooling said reaction product to room temperature and forming a liquid pourable syrup, which is suitable for in situ polymerization, a relatively larger amount of such a catalyst is added, and optionally the resulting syrup with an inert additive which is soluble in water or alcohol, such as flavor, perfume, pharmaceutical agent, antiseptic agent added. The casting syrup may be suitably colored and pigmented, and its viscosity may be increased to the desired level by adding appropriate thickening agents.

The pouring syrup can be cured to produce products that can be cast, molded or processed by machining into bars, plates, etc. for various uses. The polymer obtained from the cured casting syrup has good mechanical strength, reversible liquid absorbency, and the ability to maintain its shape in a liquid medium and regain this shape upon deformation by elastic recovery.

The casting syrup is suitable, for example, for in situ polymerization in the manufacture of dental prostheses, - 3 -

No.312930 especially in the production of denture linings and mouthguards. The absorbency of the cured product also allows advantageous use for other medical-surgical purposes such as heart valves, vascular exchange material, dialysate diaphragms, or intrauterine devices.

Prior to the addition of dyes, pigments, thickeners and other additives, the liquid casting syrups are added to an excess amount of water to form a polymer precipitate. The latter is soluble in highly polar organic solvents such as alcohols, glycols and glycol ethers. The precipitated polymer, when dissolved in polar solvents, is used as a polymer solution to form films, coatings, and the like. used. Deviating from this, the precipitated polymer can be dried and used for the production of molded articles by casting, injection molding, extrusion, calendering and the like. be used.

One embodiment of the invention comprises mixing a major portion of the monoester with the vinyl polymerization catalyst in an anaerobic atmosphere and heating the mixture to a temperature between room temperature and about 80 ° C until said monomer has become water insoluble, then the resulting mixture cooled to room temperature and a smaller amount of a polymerizable diester of an olefinic acid, in particular an aj3-unsaturated carboxylic acid, for example of acrylic or methacrylic acid, and an alcohol having at least two esterifiable hydroxyl groups, together with a further small amount of one of said catalyst, sufficient to form a liquid pourable syrup which is suitable for a in situ polymerization is suitable.

Examples of usable hydroxyalkyl monoesters of an α, β-unsaturated carboxylic acid are the 2-hydroxyethyl methacrylate and the hydroxypropyl methacrylate. For example, tert-butyl peroctoate, isopropyl percarbonate or benzoyl peroxide are suitable as free-radical catalysts. Ethylene glycol dimethacrylate, 1,3-butylene glycol dimethacrylate or 1,4-butylene glycol dimethacrylate are examples of useful diesters.

The free radical catalyst is suitably used in concentrations of 0.05 to 1 g of catalyst / 100 g of polymerizable hydroxyalkyl monoester, preferably 0.1 at 0.2 g / 100 g of starting material.

The diesters can be used in quantities of 100 g of 2-hydroxyethyl methacrylate, preferably from 0.1 to 1.0 g / 100 g of polymerizable hydroxyalkyl esters.

The polymerization of the above-mentioned reaction components can be accelerated by heat application, or it can also by certain selection of the catalyst and the amount thereof, the application of heat ceases and yet rapid polymerization is already initiated at room temperature.

Preferably, the mixing of the reaction components in an inert atmosphere and in a temperature range between room temperature and 80 ° C.

Small amounts of one or more additives such as synthetic resins, rosin esters, phenoxy resins, silicone resins, low molecular weight polyisobutylenes, synthetic polymers and prolamins can be incorporated in the casting syrups. The resulting compositions are particularly suitable for the formation of polymer mixtures which are equipped with new properties and show an improvement or enhancement of the already existing properties of the hydrophilic polymers.

If replacement materials for vessels of the human body are produced from the casting syrups obtainable according to the invention, materials of new and technically excellently useful properties are obtained. In addition to the inherently required properties, such as chemical, physical and thermal inertness, the replacement vessels made from the irrigating syrups obtainable according to the present invention are characterized by their unusual colloidal properties, which make them closely related to living tissue, and are therefore predestined for a longer lasting contact with body tissues.

A totally unexpected advantage of the articles made from the presently available pour syrups is that due to their reversible liquid absorbency, heparin or other anticoagulant dissolved in an isotonic saline solution is added in a suitable solvent during polymer preparation and the polymerization is then in situ can be carried out. The anticoagulant is then present in the replacement vessel and is gradually released after transplantation, preventing thrombus formation.

The pourable syrups obtainable according to the invention are also suitable for the production of other prosthetic devices, such as body implants, and contraceptive devices, such as uterine inserts, diaphragms. To impart sufficient rigidity to the end products, it is advantageous to incorporate filler into the casting syrup prior to final cure. The filler material may consist of an inert salt, such as Barium sulfate, calcium carbonate or clay exist.

The hydrophilic polymers which can be prepared from the casting syrups obtainable according to the invention are also an excellent filter medium for industrial purposes, because they have the ability to retain and release other components, such as thiourea or dithioerythritol, which latter - 4 -

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Components are resistant to oxidation and therefore available for the reaction with the toxic, irritating or odor-causing combustion products of the blown smoke and convert them into a non-harmful form.

From the hydrophilic casting syrups obtainable according to the invention, it is also possible to prepare powders as thickening agents for foods, as well as bandages or bandages containing medicaments.

Water-soluble nutrients can also be added to the watering syrups, which can then be released again under controlled conditions.

Example 1: 2-Hydroxyethyl methacrylate (100 parts) is combined with tert-butyl peroctoate (0.05 part) at 25 ° C in an inert atmosphere. This mixture is combined with "nylon-6" (100 parts) in trifluoroethanol (85 parts); This gives you a clear solution. This solution is heated to 65 to 70 ° C for the preparation of a prepolymer. The prepolymer solution is cooled to 25 ° C and then tert-butyl peroctoate (0.10 parts) and ethylene glycol dimethacrylate (0.02 parts) are added.

For example, fibers can be made from the resulting viscous pouring syrup. The fabrics made from these fibers are exceptionally supple in their texture and have a very soft feel.

Example 2: The procedure of Example 1 is repeated with the modification that a mixture of isomeric hydroxypropyl methacrylates is used in place of hydroxyethyl methacrylate.

Example 3: The procedure of Example 1 is repeated but modified by using cumene-α-hydroperoxide as the free radical vinyl polymerization catalyst.

EXAMPLE 4 2-Hydroxyethyl methacrylate (100 parts) is stirred with 0.05 part of tert-butyl peroctoate in a nitrogen atmosphere for 30 minutes at a temperature of 30 or 40 ° C. The resulting mixture is cooled to 25 ° C, and so much tert-butyl peroctoate is added that the total amount of tert-butyl peroctoate added to the system is 0.15 part. At the same time, ethylene glycol dimethacrylate (0.1 part) is added.

Example 5: The procedure of Example 4 is repeated, except that 0.2 part of 1,3-butylene glycol dimethacrylate is used in place of ethylene glycol dimethacrylate.

Example 6: 2-Hydroxyethyl methacrylate (100 parts) is stirred with tert-butyl peroctoate (0.1 part) in an anaerobic atmosphere for 20 minutes at a temperature of 40 ° C. The resulting mixture is cooled to 25 ° C and tert-butyl peroctoate (0.05 part) is added. Ethylene glycol dimethacrylate (0.2 parts) is added simultaneously with the catalyst. The result is a casting solution which, after curing, gives a substantially completely (99.5%) fully polymerized polymerization product which has a smooth, non-sticky surface.

Example 7: The procedure of Example 6 is repeated except that a catalyst mixture consisting of 0.05 part of tert-butyl peroctoate and 0.1 part of isopropyl percarbonate is used. The catalyst concentration is brought to the theoretical value by addition of isopropyl percarbonate.

Example 8: The procedure of Example 6 is repeated with the modification that in the casting syrups BaSO₄ (50 parts) is mixed.

Example 9: Distilled 2-hydroxyethyl methacrylate (100 g) is stirred with 0.1 g of tert-butyl peroctoate in an anaerobic atmosphere at 25 to 70 ° C. for 15 to 40 minutes. The resulting mixture is cooled to 25 ° C, and so much tert-butyl peroctoate is added that the total concentration of tert-butyl peroctoate in the system is 0.2 g per 100 g of 2-hydroxyethyl methacrylate. At the same time, when the catalyst concentration is brought to the theoretical value, ethylene glycol dimethacrylate is added in a concentration of 0.2 to 100 g of 2-hydroxyethyl methacrylate. Thereafter, microfine silica having a particle size of 0.15-0.02 microns is mixed into the casting syrup to obtain a prepolymer syrup having such rheological properties as desired for use as a denture base stock.

Example 10 The procedure according to the procedure of Example 9 is followed except that hydroxypropyl methacrylate is used instead of 2-hydroxyethyl methacrylate.

Example 11: The procedure of Example 9 is repeated except that isopropyl percarbonate is used as the catalyst and 1,3-butylene glycol dimethacrylate is used in place of ethylene glycol dimethacrylate.

Example 12: Distilled 2-hydroxyethyl methacrylate (100 g) is stirred with 0.05 t-butyl peroctoate for 14 to 40 min in an anaerobic atmosphere at 25 to 70 ° C. The resulting mixture is cooled to 25 ° C and further tert-butyl peroctoate is added in such an amount that the total concentration of tertiary butyl peroctoate in the system is 0.15g / 100g 2-hydroxyethyl methacrylate. Now, ethylene glycol dimethacrylate in a concentration of 0.15 g / 100 g of 2-hydroxyethyl methacrylate is added, and at the same time the catalyst concentration is brought to the theoretical content. Peppermint oil (11.10 parts) is also added as a flavoring to the casting syrup to obtain a flavored prepolymer syrup which is storable. After hardening and granulation, the - 5 -

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Flavor-bearing granules are added as the aroma gradually releasing component to chewing gum, gelatin and tablets against the heartburn.

Example 13: To 90 g of a base pouring syrup prepared according to Example 9, with stirring, 0.15 g of tert-butyl peroctoate are added within 15 to 40 minutes at 25 to 70 ° C in an anaerobic atmosphere, the used Monom ereiun close is adjusted so that 90 g of a finished pouring syrup arise. The resulting mixture is cooled to 25 ° C and so much t-butyl peroctoate is added that the total concentration of tertiary butyl peroctoate in the system is 0.15 g / 100 g 2-hydroxyethyl methacrylate amounts. Ethylene glycol dimethacrylate is added in a concentration of 0.15 g / 100 g of 2-hydroxyethyl methacrylate at the same time that the catalyst concentration is brought to the theoretical level. Thereafter, peppermint oil (10 g) is added to the casting syrup to form the flavored stock solution.