Cross-linked hydrogels, process for preparing thereof and their application as a wound cover

The invention relates to cross-linked hydrogels based on polyhydric alcohols, biopolymers and synthetic polymers, as well as their use as medical wound dressings.

In recent years, a number of hydrogel colloidal systems that serve as wound covers have been marketed, which have a high absorption capacity for wound secretions, so that they can be left on the wound for several days, which has the advantage of undisturbed wound healing to eliminate bacteria.

Examples of such materials are described in the following patents:

CA-A 1 180 622 gelatin + polyethylene oxide + polyethyleneimine

DE-C 28 49 570 hydrophilic poly / meth / acrylic acid derivative in the presence of a mixture of a polysaccharide and a protein

DE-C 30 31 304 bases: hydrophilic ethylenically unsaturated monomers cross-linked with difunctional compounds

EP-B 0 099 758 synthetic collagens or alginates and other biopolymers

EP-B 0 262 405 polyacrylate / polyacrylic acid / acryloylamide and other acrylamide derivatives

EP-B 0 272 074 copolymers of unsaturated monomers containing carboxyl groups + disaccharides or oligosaccharides

US-A 3,249 109 gelatin, water polyhydric alcohols, pectin

US-A 4,243,656 polyacrylate dispersion +. moisture absorbent, gelatin, water.

However, the wound covers thus produced show a number of drawbacks in practical use.

Biopolymer-based hydrogels lose sufficient mechanical strength after absorption of wound secretions, since the purely physical crosslinks there exist are not sufficiently stable at high absorption. At body temperature it dissolves in the secretion of the wound and cannot be completely removed from the wound. In addition, such hydrogels are not transparent, so it is not possible to observe the wound without changing the dressing.

Hydrogels of synthetic polymers do not tend to continuously absorb wound secretions. The absorption capacity is already exhausted after a relatively short time (about 2-3 hours).

This also applies to the products of DE-C 28 49 570 and US-A 3,249 109, which can be regarded as the closest prior art.

SUMMARY OF THE INVENTION It is an object of the present invention to provide hydrogel-absorbing hydrogels that do not have the above drawbacks.

The problem is solved according to the invention by cross-linked hydrogels based on a combination of polyhydric alcohols, biopolymers and synthetic polymers, wherein the biopolymers and the synthetic polymer are cross-linked to each other.

Accordingly, the present invention provides an elastic wound cover, absorbing the secretion of the wound, which is transparent and formed as a film and is obtainable from polyhydric alcohols, biopolymers and synthetic polymers, and crosslinking of biopolymers with synthetic polymers.

The hydrogels of the invention are made up of the following components:

and / 20 to 70 wt. % of at least one polyhydric alcohol b / 10 to 35 wt. % of at least one natural gelling agent (biopolymer) c) 0.05 to 12 wt. % of at least one non-crosslinked copolymers comprising one or more vinyl carboxylic acids and their salts (synthetic polymer) d) 0.05 to 10 wt. % of crosslinker e / 0 to 50 wt. water or saline.

Of the polyhydric alcohols, glycerin is preferred, which may be used alone or in admixture with other polyhydric alcohols.

Other polyhydric alcohols are ethylene glycol, diethylene glycol, 1,2-propanediol, 1,2-butanediol, 1,3-butanediol, 2,3-butanediol, 1,4-butanediol, glycerin monoacetate or a mixture of these alcohols.

As the natural gelling agent (biopolymer), gelatin alone is used or is used in admixture with other biopolymers, alginates are preferred. Particularly preferred is a combination consisting of gelatin and sodium alginate in a weight ratio of 5: 1 to 30: 1.

Other biopolymers which may be used alone or in admixture with gelatin include collagens and pectins.

The non-crosslinked copolymer used as a synthetic polymer is built from at least one vinylcarboxylic acid and at least one alkali metal or ammonium salt. Of the vinyl carboxylic acids, acrylic acid, methacrylic acid and / or β-acryloyxloxypropionic acid are preferred. Other suitable vinyl carboxylic acids are vinyl acetate, maleic acid, fumaric acid, crotonic acid, aconitic acid, itaconic acid, and mixtures thereof.

The crosslinking agents used according to the invention are preferably selected from the group of metal chelates, orthotitanium acid estar, epoxides, azitidines, triazines or melamine formaldehyde resins. Particularly suitable herein are aziridines and a metal chelate group, for example acetylacetonates, for example transition metal acetylacetonates such as titanacetylacetonate, zirconacetyl acetonate. The crosslinking means induces the crosslinking of the biopolymers with the synthetic polymer to a preferably three-dimensional network.

The wound secretion-absorbing hydrogel according to the invention is prepared by homogenizing the components, optionally with stirring and heating.

In this case, it is advantageous to add the crosslinker to the homogeneously mixed mass of the other components. The polymer mass thus obtained is then applied to a metallized (preferably aluminized) carrier film of suitable synthetic material, in particular PETP, and heated, for example, to 100 ° C for 20 minutes. A transparent, elastic film is obtained as the finished product.

The hydrogel according to the invention exhibits surprisingly high water vapor permeability as well as elasticity and flexibility compared to synthetic polymer and biopolymer based hydrogels. Furthermore, the hydrogel according to the invention absorbs wound secretion continuously over a comparatively long period and clearly exceeds in its absorbency the commercially available hydrogel based on synthetic polymers, which after a comparatively short time reach their maximum absorption. The combination of the absorption and high vapor permeability of the hydrogels of the present invention creates a constant moist environment on the wound, leading to accelerated healing. In addition, the hydrogels of the invention are transparent and thus allow the wound healing process to be observed, so that in low secreting wounds the dressing can change at longer intervals.

The hydrogels according to the invention excel above the known biopolymers hydrogels in addition to transparency, elasticity and flexibility, in particular in that they do not dissolve in the secretion of the wound.

The invention further relates to the use of the hydrogels according to the invention as a wound cover.

The invention is further illustrated by the following Examples

A mixture consisting of 70 g glycerin, 30 g gelatin, 30 g water and 5.4 g acrylic acid / sodium acrylate copolymer (18% solution in glycerine / water 3: 1) is homogenized in a 1 liter flask with stirring at 95 ° C. . The molten homogeneous mass is supplemented with 18 g of titanacetylacetonate as a 10% alcoholic solution.

The thus prepared polymer mass is coated with aluminized PETP film and heated to 100 ° C for 20 minutes. A transparent, elastic film is obtained as a finished product, the properties of which are given in the table.

Example 2

To the molten mass described in Example 1 is added 30 g of aluminum acetyl acetonate as a 5% ethyl acetate solution. The hydrogel properties of the obtained coating and drying (20 minutes at 100 ° C) are shown in the following table.

Example 3

Finally, as shown in Example 1, a mixture consisting of 60 g glycerin, 10 g 1,2-propanediol, 35 g gelatin, 45 g water and 6.2 g copolymer of β-acryloylosypropionic acid / 15% solution in a mixture of glycerin and water 4 The solution is homogenized with stirring at 95 ° C. The molten mass is mixed with 4.5 g of melamine-formaldehyde / resin and processed to the finished product as described in Example 1. The test values ​​can also be seen from the table.

For comparison, hydrogel films based on biopolymers as well as synthetic polymers were used, the properties of which are also shown in the following table.

marking thickness color transpa- elasti- flexibili- maximum

<td>product</td><td>/ mm /</td><td>rence</td><td>čita</td><td>the</td><td>stress /% /</td>

<td>Cutinova⁺</td><td> 0,23</td><td>bez- trans-</td><td>none</td><td>none</td><td> 45</td>

<td></td><td></td><td>color parent-</td><td>because</td><td></td><td>/ sieve</td>

<td></td><td></td><td>her</td><td>amplification</td><td></td><td>jerks /</td>

<td>Varihe- sive</td><td> 1,50</td><td>honey none</td><td>none</td><td>none</td><td> 60</td>

<td>Example 1</td><td> 0,56</td><td>nažlou-trans-</td><td>Good</td><td>very</td><td>fle- 83</td>

<td></td><td></td><td>tlá parent-</td><td></td><td colspan="2">xibilní</td>

<td>Example 2</td><td> 0,58</td><td>her nažlou-trans-</td><td>Good</td><td>very</td><td>fle- 105</td>

<td></td><td></td><td>tlá parent-</td><td></td><td colspan="2">xibilní</td>

<td>Example 3</td><td> 0,60</td><td>her nažlou-trans-</td><td>Good</td><td>very</td><td>fle- 210</td>

<td></td><td></td><td>tlá parent-</td><td></td><td colspan="2">xibilní</td>

<td></td><td></td><td>her</td><td></td><td></td><td></td>

<td colspan="2">product designation</td><td>stickiness</td><td>WDD</td><td></td><td>absorption</td>

<td></td><td></td><td></td><td>/ g / m³</td><td>24 h /</td><td>water / 24 h /</td>

<td> -</td><td></td><td></td><td></td><td></td><td>wt. %</td>

<td>Cutinova^1-</td><td></td><td>none</td><td> 39</td><td></td><td> 500</td>

<td>Varihesive</td><td> ++</td><td>sticks strongly</td><td> 2 085</td><td></td><td> 360</td>

<td>Example 1</td><td></td><td>good adhesion</td><td> 3 461</td><td></td><td> 483</td>

<td>Example 2</td><td></td><td>good adhesion</td><td> 2 603</td><td></td><td> 450</td>

<td>Example 3</td><td></td><td>good adhesion</td><td> 2 477</td><td></td><td> 468</td>

+ Cutin: composition: polyvinyl alcohol == Varihesive: composition: gelatin, carboxymethylcellulose, tackifying resin