Reticled hydrogels used for wounds treatment

The invention relates to cross-linked hydrogels used for the treatment of wounds, based on polyvalent alcohols, biopolymers and synthetic polymers.

Hydrogel / colloid systems are known as wound coatings, which have a high absorption capacity for wound secretions, so it is possible to stay for several days on the wound with the advantage of wound healing and excluding bacteria.

Thus, different hydrogels are known which consist of gelatin, water, polyvalent alcohols and pectin or polyacrylate dispersion with a moisture, gelatin and water absorber.

It is also known a dressing for the treatment of thermal burns consisting of non-absorbable cotton mesh with 9 ... 12 mesh / cm² which is impregnated for every 1800 cm² with 2 g of ointment base containing 0.5% neomycin, 400 mg hydrocortisone acetate, 60000 IU vitamin A and 30000 IU vitamin D2.

However, such coatings for wounds present in their practical application a number of disadvantages.

Biopolymer-based hydrogels do not have sufficient mechanical strength after absorption of wound secretion, because the purely physical cross-linking there does not provide sufficient stability. They dissolve at body temperature in the secretion of the wound and can be removed from the wound without leaving a residue on it. In addition, such hydrogels are not transparent, so it is not possible to observe the wound without changing the dressing.

In contrast, the hydrogels in the synthetic polymers tend to discontinue the absorption of wound secretion. In this case, the absorption capacity of the wound is already exhausted after a relatively short time (about 2 ... 3 h).

It is an object of the present invention to obtain a resilient wrap coating in the form of a transparent, absorbent film for wound secretion, which is obtained from polyvalent alcohols, synthetic biopolymers and polymers and cross-linking of biopolymers with synthetic polymers.

The hydrogels, according to the invention, consist of: 20 ... 70% at least one polyvalent alcohol selected from glycerin, ethylene glycol, diethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 2,3-butanediol, 1 , 4-butanediol, glycerine monoacetate or mixtures thereof, preferably glycerin, 10 ... 35% at least one natural gelling agent, selected from collagen, gelatin, pectin or mixtures thereof, or a gelatin-sodium alginate mixture, preferably gelatin, 0.05 ... 12% at least one non-crosslinked copolymer of one or more vinylcarboxylic acids, selected from acrylic acid, methacrylic acid or heta-acryloylpropylic acid, vinyl acetic acid, maleic acid, fumaric acid, crotonic acid, aconitic acid, acid itaconic acid or their mixtures and alkali and / or ammonium salts of vinylcarboxylic acids, 0.05 ... 10% of a cross-linking agent selected from the group of metal chelates, ester, orthotitanic acid, epoxides, azirines, triazines or melamine-formaldehyde resins and 0 ... 50% water or physiological sodium chloride solution, the parts being expressed by weight.

The gelatin / sodium alginate crosslinking agent is used in a ratio of 30: 1 ... 5: 1, and the ratio polyvinylcarboxylic acid / polyvinylcarboxylic acid salt in the copolymer is 10: 1 ... 1:10.

The following are 10 examples of embodiments of the invention.

Example 1. In a one-liter flask, a mixture of 70 g glycerin, 30 g gelatin, 30 g water and 5.4 g copolymer of acrylic acid and acrylate is homogenized under continuous stirring at 95 ° C. sodium (18% solution in glycerin / water 3: 1). To the molten homogeneous mass is added 18 g titanium acetylacetonate as a 10% alcoholic solution.

Apply the polymer mass, thus obtained, on an aluminum foil and warm for 20 minutes at 100 ° C. As a finished product, a transparent elastic foil is obtained whose properties are indicated in table 1.

Example 2. To the molten mass, described in Example 1, 30 g of aluminum acetylacetonate are added as a 5% ethylacetate solution by mixing. The properties of the hydrogel obtained after application on aluminum foil and drying (20 min at 100 ° C) are shown in table 1.

Example 3. It is similar to Example 1. A mixture of 60 g glycerin, 10 g is stirred under continuous stirring at 95 ° C.

1,2-propanediol, 35 g gelatin, 45 g water and 6.2 g copolymer beza-acryloxyloxypropionic acid and potassium beta-acryloxyloxypropionate (15% solution in glycerin / water 4: 1). The molten mass is mixed with 4.5 g melamine / formaldehyde resin and processed as in Example 1.

Example 4. In order to obtain the hydrogel, according to the invention, the following ingredients are combined: 51 g glycerin,

21.9 g gelatin, 3.9 g acrylic acid / sodium acrylate, 1.3 g titanium acetylacetonate and

21.9 g of water. To obtain the polymer table, proceed as above.

Example 5. In order to obtain the hydrogel, according to the invention, the following ingredients are combined: 51.4 g glycerin,

21.9 g gelatin, 4.0 g acrylic acid / sodium acrylate, 0.8 g aluminum acetyl acetate and 21.9 g water.

Example 6. In order to obtain the hydrogel, according to the invention, the following ingredients are combined: 43.6 g glycerin / 1,2-propanediol mixture, 21.8 g gelatin,

3.9 g beta-acryloxyloxypropionic acid / potassium befaacryloxyloxypropionate, 2.7 g melamine / formaldehyde resin and 28.0 g water.

Example 7. In order to obtain the hydrogel according to the invention, the following ingredients are combined: 20 g 1,2-propanediol, 10 g gelatin, 12 g beta-acryloxyloxypropioant 5 sodium, 10 g 20% ​​titanium acetylacetonate solution and 48 g water.

Example 8. In order to obtain the hydrogel according to the invention, the following ingredients are combined: 70 g glycerin, 28 g 10 collagen, 1.95 g potassium acrylate polymer and acrylic acid and 0.05 g resinamelamine / formaldehyde.

Example 9. To obtain the hydrogel, according to the invention, the following ingredients are combined15: 45 g glycerin, 35 g gelatin, 10 g sodium acrylate polymer / acrylic acid, 1.0 g melamine / formaldehyde resin and 9.0 water.

Example 10. In order to obtain the hydrogel 20, according to the invention, the following ingredients are combined: 30 g ethylene glycol, 35.0 g gelatin, 0.05 g 6-potassium acryloyloxypropionate, 5.0 g 5% aluminum acetylacetonate solution and 29.95 physiological solution of 25 sodium chloride.

Beta-acryloxyloxypropionate sodium is used in 15% solution, in glycerin / water mixture 3: 1.

Potassium acrylate polymer and acrylic acid 30 are 20% solution in 4: 1 glycerol / water mixture.

Sodium acrylic polymer and acrylic acid are used in 15% solution in glycerin / water mixture 5: 1.

Potassium beta-acryloxyloxypropionate is used in 20% solution in glycerin / water mixture 3: 1.

Table 1

<td>Characterization of the product</td><td>Thickness (mm)</td><td>color</td><td>Transparency</td><td>elasticity</td><td>flexibility</td>

<td> 1</td><td> 2</td><td> 3</td><td> 4</td><td> 5</td><td> 6</td>

<td>Cutinova^x)</td><td> 0,23</td><td>colorless</td><td>transparent</td><td>does not have (reinforced)</td><td>does not have</td>

<td>Varihesive ''</td><td> 1,5</td><td>honey</td><td>does not have</td><td>does not have</td><td>does not have</td>

<td>Example 1</td><td> 0,56</td><td>yellowish</td><td>transparent</td><td>Hi</td><td>very good</td>

<td>Example 2</td><td> 0,58</td><td>yellowish</td><td>transparent</td><td>Hi</td><td>very good</td>

<td>Example 3</td><td> 0,60</td><td>yellowish</td><td>transparent</td><td>Hi</td><td>very good</td>

s

Table 1 (continued)

<td>Characterization of the product</td><td>Maximum dilation</td><td>Adhesion</td><td>WDD (G / m² 24 h)</td><td>Water processing (% in g, 24 h)</td>

<td> 1</td><td> 7</td><td> 8</td><td> 9</td><td> 10</td>

<td>Cutinova</td><td> 45</td><td>does not have</td><td> 39</td><td> 500</td>

<td>Varihesive</td><td> 60</td><td>strong</td><td> 1085</td><td> 360</td>

<td>Example 1</td><td> 83</td><td>Hi</td><td> 3461</td><td> 483</td>

<td>Example 2</td><td> 105</td><td>Hi</td><td> 2603</td><td> 450</td>

<td>Example 3</td><td> 210</td><td>Hi</td><td> 2477</td><td> 468</td>

x) Cutinova: Polyvinyl alcohol xx) Varihesives: Mixture of gelatin, carboxymethylcellulose and adhesive-producing resin. WDD: Permeability to water vapor.

Therefore, for the purpose of comparison, biopolymer-based and synthetic polymer-based hydrogel films were used. From the ones shown in the table above, the following results: 5

The hydrogels examined show a different absorption pattern, the commercial polymer based synthetic hydrogel (Cutinova) reaching its maximum absorption already after 2 to 3 h.

Compared to the other hydrogels, the hydrogel obtained according to the invention shows an excellent water vapor permeability (WDD), which, in combination with a permanent absorption of the wound secretion, leads to the fact that, regardless of the intensity of the secretion, it dominates the wound all the time. a constant humid environment that promotes healing.

The cross-linked hydrogels may also contain: at least one polyvalent alcohol selected from glycerin, ethylene glycol, diethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,2-butanediol,

1,3-butanediol, 2,3-butanediol, 1,4-butanediol, glycerinmononoacetate or mixtures thereof, preferably glycerin, at least one gelling agent selected from collagen, gelatin, pectin or mixtures thereof, or a gelatin-alginate mixture. sodium, preferably gelatin, at least one non-crosslinked copolymer of one or more vinylcarboxylic acids selected from acrylic acid, methacrylic acid or beta-crylohyloxypropionic acid, vinyl acetic acid, maleic acid, fumaric acid, crotonic acid, aconitic acid, itaconic acid or mixtures thereof and alkaline and / or ammonium salts of vinylcarboxylic acids, from a cross-linking agent selected from the group of metal chelates, orthotitanic acid ester, epoxides, aziridines, triazines or formaldehyde-melamine resins and water or physiological solution of sodium chloride.

As polyvalent alcohol, glycerin may be used which can be used alone or in combination with other polyvalent alcohols.

As a natural gelling agent (biopolymer) it is used, first of all, gelatin alone or in combination with other biopolymers, preferably alginates. Particularly preferred is a combination of gelatin and sodium alginate in weight ratio from 5: 1 to 30: 1.

Other biopolymers, which can be used alone or in combination with gelatin, are cola20 geniuses and pectins.

The copolymer used as a synthetic polymer, which the copolymer is non-crosslinked, is made up of at least one vinylcarboxylic acid and at least one of its alkali or ammonium salt. As vinylcarboxylic acids, acrylic, methacrylic, and / or feefcz-acryloyloxypropionic acid are preferred, other suitable vinylcarboxylic acids are vinyl acetic acid, maleic acid, fumaric acid, crotonic acid, aconic acid, and itaconic acid.

The agents used according to the invention are, preferably, from the group of metal chelates, orthotitanic acid ester, epoxides, aziridines, triazines or melamine-formaldehyde resins. Particularly preferred are the acetyl acids and the group of metal chelates, for example acetyl acetone, for example transition metal acetylacetonates, such as titanium or zirconium acetylacetonate. The crosslinking agent performs the cross-linking of the biopolymer with the synthetic polymer to the three-dimensional networks, preferably.

The absorbent hydrogel of the wound secretion according to the invention is obtained by homogenizing the components, possibly under stirring and heating. In this case, it is appropriate to add the crosslinking agent to the already homogeneously mixed mass of the other components. The polymer mass thus obtained is then applied to a metallic carrier film (preferably aluminum) of a suitable synthetic substance and heated, for example 20 minutes, to 100 ° C. As a finished product, a transparent elastic foil is obtained. 20

The hydrogel, according to the invention, has a surprisingly high permeability for water vapor, as well as elasticity and flexibility compared to hydrogels based on synthetic polymer and biopolymers. Then the hydrogel, according to the invention, takes up the secretion of uninterrupted wounds over a relatively long period of time and is far superior in terms of absorption behavior over the synthetic polymer-based hydrogel, which already reaches a comparatively shorter time at its absorption is high. The combination of the absorption and the permeability of the high water vapor of the hydrogels, 35 according to the invention, forms on the wound a constant humid environment which leads to an accelerated cure. The hydrogels, according to the invention, are additionally transparent and thus give the possibility of an observation of the wound healing, so that in wounds which are weak, the dressing can be changed at longer intervals.

Compared to the hydrogels known based on 45 biopolymers, the hydrogels according to the invention are superior - apart from the fact that they are transparent, more elastic and more flexible - and especially because they do not dissolve in the secretion of the wound.