Method of obtaining a network hydrogel

The present invention relates to a process for the preparation of crosslinked, wound-absorbing secretions from hydrogels based on polyhydric alcohols, biopolymers and synthetic polymers, suitable for use as medical wound coatings.

In recent years, a number of hydrogel / colloid systems have been found on the market as lead yellow¹on wounds that have a high absorption capacity for wound secretions, so that it is possible to remain on the wound for several days, resulting in an undisturbed healing process and preventing access of bacteria.

Examples of such hydrogel materials are described in the following patents j

CA No. 0 180 622 - gelatine and polyethylene glycol

DE No. 6o 4o 570 - hydrophobic derivative of the pii ^ / π ^ acid in the presence of polysaccharide / protein;

DE No. 30 31 304 - Hydrophilic ethylenically unsaturated mkekmlry, broken down with bifunctional compounds;

EP No. 0 Oi99 751 - synthetic collagen or alginates and other i ^ o ^ m-yj

EP No. O 22o 405 - sodium sodium / polylacrylic acid / acryloylamide and other acrylic acid amide derivatives;

EP No. 0 272 074 - unsaturated copolymers containing carboxyl groups of mer + disaccharides or kthosaccharides;

US-A No. 3.249.109 - gelatin, water, polyhydric alcohols, pectin:

US-A No. 4.243.656 - polyacrylate dispersion + moisture absorber, gelatin, water.

However, such wound coatings have a number of disadvantages in practical application.

Biopolymer-based hydrogels after absorption of wound secretions have insufficient mechanical strength, since the purely physical crosslinking there with high absorption does not provide sufficient stability. They dissolve at body temperature in the discharge from the wound and cannot therefore be removed from the frame without residue. Except

163 801 of this, such hydrogels are not transparent, so that it is not possible to observe the wound without changing the dressing. On the other hand, synthetic polymer hydrogels have a tendency to discontinue wound discharge. The absorption capacity is exhausted after a relatively short time (about 2-3 hours).

These arguments also apply to products according to patent specifications OE No. 28 49 570 and US-A No. 3.249.109.

The prior art is the solution according to US-A No. 4,233,656 regarding a wound dressing with a biopolymer-based hydrogel, forming a vapor-permeable film. It contains 10 to 40% by weight of a water-soluble acrylic polymer with 50 to 500 monomer units, 2 to 13% by weight of a moisture dispenser selected from the group consisting of glycol, polyethylene glycol and 1,2-diol propyl as well as 0.5 to 20 % by weight gelatin material and finally 30 to 87.5% by weight water. The wound dressing thus produced, however, has a number of significant disadvantages with regard to practical use. The biopolymer-based hydrogel after absorption of wound secretions has insufficient mechanical strength, because the purely physical wetting occurring there at high absorption does not provide sufficient stability. It dissolves at body temperature in wound secretions and cannot therefore be removed from the wound without residue. In addition, such hydrogels are also not transparent, so that it is not possible to observe the wound without changing the dressing.

Due to the low mechanical strength in the contrasted US patent, it has been proposed to reinforce the polymerized film preferably with the help of a matrix material, e.g. nylon, to achieve the necessary stability. The desired flexibility of a wound dressing with a film reinforced with a nylon matrix is ​​absolutely unsatisfactory. With respect to properties, it is stated inter alia that the film formed from the mixture is liquefied upon heating at a temperature between 35 and 40 ° C. On contact with liquid, the dressing unwinds from the body.

Thus, a biopolymer-based hydrogel, which consists mainly of a polyacrylate dispersion, moisture absorber, gelatin and water, exhibits those unfavorable properties that the present invention has to overcome. The task was solved according to the invention by developing a method for producing cross-linked hydrogels based on a composition consisting of polyhydric alcohols, biopolymers and synthetic polymers, whereby the biopolymers and the synthetic polymer are cross-linked with each other.

The subject of the invention is therefore a method of producing a wound-absorbing, transparent, film-like, flexible wound coating that can be obtained from polyhydric alcohols, biopolymers and synthetic polymers by crosslinking biopolymers with synthetic polymers.

Hydrogels prepared according to the invention contain the following components:

a / 2O-7C% by weight of at least one alcoholic acid, b / 10-35% by weight of at least one natural gelling agent (biopolymer), c / 0.05-12% by weight of at least one co-polymerization of one or several vinylcarboxylic acids and their salts / synthetic polymer /, d / 0.05-10% by weight. Securing medium, e / 0-50% by weight of water or physiological saline solution.

Glycerin is preferred as alcoholic acid, which can be used alone or in a mixture with further alcohols. Other polyhydric alcohols are ethylene glycol, di-ethyl glycol, 1,2-propandiol, 1,3-propandiol,

1,2-butandiol, 1,3-butandio1,2,3-butandiol, 1,4-butandiol, glycerol monoacetate or mixtures of these alcohols. As natural gelling agents (biopolymer), primarily gelatin is used alone or in a mixture with other biopolymers, preferably elginates. A combination of gelatin and sodium alginate in a weight ratio of 5: 1 to 30: 1 is particularly preferred. Further biopolymers that are used alone or in a mixture of gelatin include collagens and pectins.

The non-acylated copolymer used as a synthetic polymer is composed of

163 801 of at least one vinylcarboxylic acid and at least one of its alkali or ammonium metal salts. Acrylic acid, methacrylic acid and / or 8-acryloyloxypropionic acid are preferred as vinylcarboxylic acids. Other useful vinyl carboxylic acids are vinylacetic acid, maleic acid, fumaric acid, crotic acid, aconltic acid, itaconic acid or mixtures of these acids.

The crosslinkers used according to the invention are preferably those from the group of chelate complexes, orthotitenoic acid esters, epoxides, aziridines, triazines or melamine-formaldehyde resins. Aziridines and a group of chalate complexes, e.g. acetylacetone ^^ n ^, e.g. transition metal acatylacatonates such as titanium or zirconium acetylacetonate are particularly preferred. the crosslinker causes the biopolymer with synthetic polymer to crosslink to preferably three-dimensional crosslinked structures.

The wound-absorbing hydrogel obtained by the process of the invention is prepared by subjecting the components to homogenization, optionally with simultaneous mixing and heating. It is advisable to add the crosslinking agent to the already homogeneously mixed mass of the other ingredients. The polymer mass thus obtained is then applied to a matalized (preferably aluminized) carrier foil of a suitable plastic, in particular PETP (polyethylene terephthalate) and heated, e.g. within 20 minutes to 100 ° C. As a finished product, a transparent, flexible film is obtained.

Compared with the synthetic polymer and biopolymer based hydrogel produced by the process of the invention, unexpectedly high water vapor permeability, as well as elasticity and flexibility. Furthermore, the hydrogel obtained by the process of the invention continuously extracts wound secretion over a comparatively long time and in its absorption behavior clearly exceeds a commercial hydrogel based on a synthetic polymer, which achieves its maximum absorption after a comparatively short time. The combination of absorption and high water vapor permeability of the hydrogels obtained by the method of the invention creates a constant moisture environment on the wound, which leads to accelerated healing. The hydrogels obtained according to the method of the invention are also transparent and thus allow the wound healing to be observed, so that with poorly exuding wounds, the dressing can be changed at longer intervals.

The hydrogels obtained by the process of the invention outweigh the known hydrogels based on biopolymers, in addition to transparency, elasticity and elasticity, primarily because they do not dissolve in the discharge from the wound. The hydrogels obtained by the process of the invention are also used as wound coatings.

The invention explains the examples below.

Example 1. A 1 L flask is homogenized with a mixture of 70 g glycerin, 30 g gelatin, 30 g water and 5.4 g copolymer of acrylic acid and sodium acrylate / 18% solution in glycerin / water 3: 1 / with continuous stirring at 95 ° C. 18 g of titanium acetylacetonate in the form of an 18% alcohol solution are added to the molten homogeneous mass. The aluminum PETP film is coated with the polymer mass prepared in this way and heated within 20 min to 100 ° C. As a finished product, a transparent, elastic film is obtained, the properties of which are given in the table.

Example II 30 g of aluminum acatylacatonate in the form of a 5% ethyl acetate solution are mixed with the molten mass described in Example 1. The properties of the obtained after coating and drying / 20 min at 100 ° C / hydrogel are shown in the table.

Example III. As in Example 1, a mixture of 50 g glycerin, 10 g 1,2-propandiol, 35 g gelatin, 45 g water and 6.2 g copolymer of (3-acryloyloxypropionic acid and potassium β-acryloyloxypropionate / 15% - is homogenized solution in glycerin / water 4: 1 / with continuous stirring at 95 ° C. The molten mass is mixed with 4.5 g of melamine-formaldehyde resin and processed as in Example 1 into the finished product. Test values ​​are also given in the table.

For comparison purposes, hydrogel membranes based on biopolymer as well as synthetic polymer based were used, whose properties are also given in the following table.

163 801

Table • ———-- 4 —— Designation-J Grunie pro-ι void depth J / mm / ii I

Color

Overwhelmingly!

Resilience in ¹^X AND

CutinovaJ and

AND

AND

AND

I • 4 '

40.23 colorless transparent no J / because J reinforces ¹niona /! --------₁

<td colspan="2" rowspan="2">{Maximum flexibility!</td><td colspan="2"></td><td rowspan="3">and Download not wo J dy / 24 h / • /% wago! in/</td>

<td rowspan="2">Klei- stość</td><td rowspan="2">J WDO ,,! / g / m, and 24 h / 1 1 1 1</td>

<td>POWER to</td><td>I am lengthening and Jżenie! ·, /% / J 1 1 1</td>

<td></td><td> 1 1</td><td></td><td> 1</td><td></td>

<td>lack</td><td>1 1 j 45 j ι / sietka and</td><td>lack</td><td> ! 39</td><td>and 500</td>

<td>XX Varihe- sive</td><td></td><td>1,50j 1 1</td><td>1 Honey J</td><td>1 no J 1 1</td><td>lack</td>

<td>At-</td><td></td><td>0.56 units</td><td>yellow-J</td><td>przezro-J</td><td>Okay</td>

<td>example</td><td></td><td> 1 1 1 1 1</td><td>wa J 1 1 1</td><td>pure J 1 1 1</td><td></td>

<td>At-</td><td></td><td> 0,58]</td><td>yellow-j</td><td>przezro-J</td><td>Okay</td>

<td>example 11</td><td> 1 1 1 1</td><td> 1 1 1 1 1</td><td>wa J 1 1 1</td><td>clean&gt; 1 1 1</td><td></td>

<td>At-</td><td> 1 1</td><td rowspan="2">and 0,60j</td><td>yellow</td><td>przezro-J</td><td>Okay</td>

<td>Quad</td><td> 1 1</td><td>tawa J</td><td>pure J</td><td></td>

<td>III</td><td> 1 1 1</td><td> 1 1 1</td><td> 1 1 1</td><td> 1 1 1</td><td></td>

L_____X_______C

J crack / III

L ......

AND

<td>lack</td><td></td><td> 60</td><td colspan="2">J sticks hard</td><td colspan="2">J 2085 1 1</td><td colspan="2"> { 360 1 1</td>

<td>very flexibility tangent</td><td> 1 1 1</td><td> 83</td><td> 1 1 1 1 1 1 1</td><td>Okay at- czep- POWER to</td><td></td><td> 3461</td><td> 1 1 1 1 1 1</td><td> 483</td>

<td colspan="2">very much 1</td><td> 105</td><td>and 1 1 1 1 1 1</td><td>Okay at- czep- POWER to</td><td> 1 1 1 1</td><td> 2603</td><td> 1 1 1 1 1 1 1</td><td> 450</td>

<td>very flexibility tangent</td><td>1 1 1 1 1 AND</td><td> 210</td><td>and 1 and 1 1 1 1</td><td>Okay at- czep- POWER to</td><td> 1 1 1 1 1 1 1</td><td> 2477</td><td>1 1 1 L 1 1 1</td><td> 466</td>

Cutinova: composition: polyvinyl alcohol ^xxVarihesive: composition: gelatin, carboxymethyl cellulose, gums

The tested hydrogels have different absorption processes, with the commercial hydrogel based on synthetic polymer / Cutinova / reaching its maximum absorption after 2-3 hours.

Compared with other hydrogels, the hydrogel obtained by the process of the invention has excellent water vapor permeability (WDD), which, in combination with the continuous uptake of secretion from the wound, leads to the fact that regardless of the strength of the secretion, the wound always has an unchanging moisture environment.

163 801

UP Department of Publications. Circulation of 90 copies

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