DE2725261A1 - Transparent liq. gels e.g. of hydrophilic acrylic! polymer and gelatin - useful as wound dressings, esp. for burns and ulcers, and as cell culture media - Google Patents

Abstract

Transparent liq. dressing, esp. for wounds, comprises a hydrophilic organic transparent gel in sheet or tape form, swollen with an aq. soln. The dressing may be reinforced with a string or net-like reinforcing agent. The aq. soln. used to swell the gel may contain buffers, wound treatment agents, nutrients and/or growth agents. Healing progress of the wound visually without removing the dressing. When it becomes necessary to change it, the old dressing can be removed easily without damage to the new tissue forming underneath. The gels are also useful as cell culture media. Pref. the gel consists of a mixt. of a hydrophilic polymer (I) and >=1 high molecular gel-forming substance. Esp. useful gels are comprised of a gel-forming polysaccharide and/or a protein or polypeptide, and a polymer of a hydrophilic (meth)acrylic acid deriv. made by polymerisation in the presence of the gel-forming substance. Suitable gel-forming substances are e.g., agarose and gelatin.

Description

Transparent liquid dressing material, its manufacture

and use.

The invention relates to a transparent liquid dressing material, in particular for the treatment of wounds, a method for its production as well its use.

The previous dressing technique for poorly healing wounds, burns, Ulcers, etc. have oriented themselves relatively unilaterally to dressing materials to develop that nestle against the wound bed and are easy to use when changing dressings, Let it dissolve without pain and without bleeding.

These dressing materials consist of grease-impregnated textiles, partly made of synthetic fabrics, partly also made of cotton.

In the course of further development these materials were then used various substances such as disinfectants or antibiotics added.

The disadvantage of these materials, however, is that they are used in the case of strongly supple wounds Here a bandage material is applied that is itself highly hydrophobic.

The fat in the tissue allows the bandage to be pulled off easily, but covers the wound relatively tightly with a film of fat, so that in the case of strongly exuding Wound surface retention of fluid can occur.

Another therapeutic principle is the use of moist bandages. This is done either by irrigation of the wounds, which are covered with gauze compresses are, with different media or - especially in dermatology - through the application of occlusive dressings.

There are two major disadvantages here: With the occlusive dressings skin macerations occur (they usually consist of a moisture-soaked Compress, which is covered with a foil). When treating with moist Associations, the constant irrigation leads to a relatively strong evaporative cold, the beds are often very difficult to keep dry, which results in larger beds nursing problems, not to mention the relatively high price of such media, which have to be used in large quantities for irrigation.

Treatment of secreting and grabbing wounds should be given made with hydrophilic materials that can be removed relatively easily and which should be transparent for the observation of possibly occurring superinfections.

The covering and treatment of large wounds and ulcerations was previously done with opaque membranes, ointments, foam or bandages. A visual check of the healing process and a recognition of complications was therefore not possible. In addition, the bandages often stick firmly to the Wound base, so that a dressing change with bleeding and disturbances of the healing process connected is. It therefore often develops as a long-term consequence of such treatment agents Scar keloids.

A synthetic skin substitute for bandage purposes is also known, that consists of an open-pored, soft polyurethane foam layer and an outer layer consists of microporous polytetrafluoroethylene film. This material is opaque and therefore has those noted above due to opacity Disadvantages as well. In addition, this material is intended to be glued to the wound, so that the granulations are torn off when peeled off. The association must therefore be changed at short intervals.

A dressing material is also known, which consists of a liquid Solvent from polyethylene glycol and a poly (2-hydroxyethyl methacrylate) in Powder form. The application is done by adding the liquid solvent to it the wound is dripped and spread on, and then the polymer powder is sprinkled on will. With this material, the production in situ on the wound is essential, the use of a liquid premix was found to be unsuitable. His whole Kind of it is not a bandage material, but something in between between ointment and liquid applied wound covering films, which is also the There are disadvantages already listed above.

The invention is therefore based on the object of a hydrophilic liquid dressing material to create what is transparent and therefore the observation of the underlying Skin areas that allow a dressing change without bleeding or other Disturbances of the healing process and which also allows the simultaneous application of substances important for wound treatment and healing made possible without the previous one to have disadvantages occurring with damp dressings.

According to the invention, this object is achieved by a transparent one Liquid dressing material, which is characterized in that it consists of a hydrophilic organic transparent gel in sheet or tape form, which present swollen with an aqueous solution, the buffer substances, in wound treatment Can contain customary active ingredients, nutrients and / or growth substances and optionally contains a reinforcing material arranged in a line or in a net-like manner.

The liquid dressing material according to the invention can be used as a transparent Describe gel layer which tb; ¢ ch typically a thickness between about 0.5 and 10 mm, preferably between 1 and 5 mm, and swollen with an aqueous solution Condition is present. The solution contains in dissolved form those for wound treatment and healing important substances, such as buffer substances, antiseptics, antibiotics, pharmaceutically active substances Substances, nutrients, growth substances and the like. All of these substances are for skin treatment or wound treatment is known and familiar to the person skilled in the art. There is no need therefore it is worth specifying them here in detail.

The fluid dressing material according to the invention can be used for physical reinforcement contain a reinforcing material, which is stored in the gel in the form of a net or line is and the individual threads or fibers must be arranged so that the transparency the material is not significantly affected by this. Preferably will the reinforcement material used in the form of a wide-meshed net. The reinforcement material consists of natural ender man-made fibers and threads opposite the solution and the actual Gel are inert.

The most important component of the liquid dressing material according to the invention is the hydrophilic organic transparent gel.

This gel preferably consists of a mixture of hydrophilic polymer and at least one gellable high molecular substance. Under the term "polymer" are understood here compounds that are synthetically made from monomeric units Polymerization, that is, polyaddition or polycondensation, were produced. It can be homopolymers or copolymers of two or more different ones act monomeric units. The polymer can also be crosslinked by metering it of monomers which have more than one group capable of addition or condensation contain. It is important, however, that the polymer is so hydrophilic that it is in aqueous Medium capable of gelling transparently. The prerequisite for this is that in the monomers Units have a sufficient number of hydrophilic groups, such as. B. OH groups, NH2 groups, COOH groups and the like are present.

In the preferred embodiment, the gel contains in addition to the above defined polymer also at least one gellable high molecular weight substance, preferably a high molecular weight natural product. These are particularly suitable the gellable carbohydrates and gellable polyamino acids and their combinations and derivatives.

The polymer and the gellable high molecular weight substance can are present next to each other as an ordinary mixture in which the components move freely are; they can be in the form of a three-dimensional network consisting of cross-linked polymer and in its pores the molecules of the gellable high molecular weight substance as if held in a cage (this structure obtained by preparing the polymer with crosslinking in the presence of high molecular weight substance) or polymer and high molecular weight substance even be linked to one another by covalent bonds.

The hydrophilic organic transparent gel is particularly preferred from a polymer of a hydrophilic acrylic acid or methacrylic acid derivative and composed of at least one gellable polysaccharide and / or protein or polypeptide.

As the hydrophilic acrylic or methacrylic acid derivative, it is particularly preferred an amide or an ester with an alkanol is used, in the latter case the Alkanol radical can also contain one or more additional free hydroxyl groups. The alkanol radical generally contains 1 to 6 carbon atoms. If no free hydroxyl groups are present, alkanols with 1 or 2 carbon atoms are preferred.

Typical examples of this preferred group of monomers for the Polymerization components of the gel material are acrylamide, methacrylamide, ethyl acrylate, Methyl acrylate, propyl acrylate, butyl acrylate and the corresponding methacrylates, Hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxybutyl acrylate, the corresponding Methacrylates, acrylic acid glycerol esters, acrylic acid erythryte esters, acrylic acid pentaerythryte esters and the corresponding methacrylic acid compounds. Used as a crosslinking agent bifunctional or polyfunctional polymerizable compounds, such as methylenebisacrylamide and the like, added. These crosslinking agents are known to the person skilled in the art and are therefore not further exemplified here.

The gel preferably contains agarose as the gellable polysaccharide. Other suitable polysaccharides are, for example, pectins, starch, dextrans, polyglycols, Cellulose derivatives and agar-agar. Essential for the suitability within the scope of the invention is the gelability, which means that transparent swollen masses must be formed will.

Gelatin is preferred among the gellable proteins or polypeptides.

The gels are preferably produced by polymerization of the monomer or monomers for the polymer component in the presence of the high molecular weight Substance in aqueous solution by adding suitable polymerization initiators, such as per compounds, for example ammonium persulfate or creating the for the Polycondensation required conditions.

The person skilled in the art is familiar with the hydrophilic ones used in each case Polymerization conditions and polymerization initiators suitable for monomers are well known, so that an enumeration of them can be omitted here.

The dressing material according to the invention is always in by aqueous Swollen state. An intermittent drainage between the manufacture and use of the dressing material should be avoided because the extremely favorable properties of the material then not fully recover can be produced. The material is expediently sterile in the completely swollen state Stored in the packaging and can then be used directly after simply opening the packaging will.

A particularly advantageous and surprising property of the invention Dressing material is that it adheres well to healthy tissue, but with the wound itself is not stuck together. This therefore enables a problem-free dressing change, if one is necessary.

As a result of the transparency or transparency of the material can also the healing process can be constantly monitored with the eye.

Since the gel is in a watery swollen state, it is above it It is also possible to use the substances to be used for wound treatment and healing without Apply dressing change by they just put them on the hook Bandage to be applied. They then diffuse through the dressing in dissolved form through to the underlying skin surface and can take effect there.

By choosing the ratio of acrylic or methacrylic acid derivative The absorbency can also be converted into gellable polysaccharide or protein and regulate the water retention capacity of the dressing material.

D The dressing material according to the invention is manufactured in Moisture-proof packaging made of plastic or metal or the like brought in, sealed in plastic films, metal foils or metal containers, for example, to prevent dehydration. For example, the bandage material is in foils sealed and several bandage panels packed in this way are placed in a plastic or packed in a metal bowl, which is then just before being placed on the wound can be used to make the bath for the dressing panels.

As mentioned, the dressing material according to the invention can already contain active ingredients dissolved included. However, the particular active ingredients desired are preferred applied shortly before applying the bandage or only afterwards, as the therapies are very different and therefore a gel sheet not yet impregnated with active ingredients Easier to adapt to the various forms of therapy through subsequent impregnation can be. For example, if a dressing material according to the invention is placed in iodine-polyvidone solution, a yellowish-orange coloration can be seen after just 5 minutes and afterwards After 10 minutes a considerable part of the iodine has evidently diffused into the material.

The material according to the invention remains even with highly secreting Wounds lie relatively unchanged on the wound bed, but dry on the edges so that a good hold is achieved from there.

Preferably, when using the dressing material according to the invention an overlying bandage was applied for his protection, which was useful consists of gauze, as this is hydrophobic and the liquid itself Withholds dressing material.

In a proven application, the dressing material according to the invention is placed on the wound in such a way that it can dry firmly at the edges, then becomes A grease-proof gauze that is relatively heavily impregnated with grease is applied, followed by a thin one Compress bandage and an elastic bandage.

Clinical tests with the dressing material according to the invention have shown that it is absolutely compatible, that it is ideally easy to use and that it is trouble-free Removal or dressing change allows. A particular advantage can be seen in that wound healing under the dressing material without excess granuloma formation accelerates, which prevents the development of scar keloids.

The bandage material according to the invention is particularly suitable for Healing of wounds, especially burns and chronic ulcerations. Other Areas of application are after-treatment of skin tumors, desensitization of allergies, cosmetic surgeries and the like.

In addition, the bandage material according to the invention can advantageously be used can also be used as a carrier for cell cultures.

The following examples illustrate the preparation of the invention Bandages.

Example 1 polyacrylamide (5%), gelatin (5%) 5 g acrylamide and 130 mg of N, N'-methylenebisacrylamide are dissolved in 50 ml of distilled water and the Solution heated to 600C. Furthermore, 5 g of gelatin are distilled in 50 ml of hot Dissolved water and also kept at 600C.

A glass plate 12.5 x 26 cm with a 2 mm high edge is on one Warming plate preheated to 65 0. The above two solutions will get warm mixed, 60 / µl N, N, N ', N'-tetramethylene diamine (TESSED) and 45 mg ammonium peroxydisulfate added quickly, mixed and immediately poured into the polymerization chamber. This is closed with a glass lid so that no air bubbles are trapped will. The cuvette is kept at 560C for approx. 30 minutes until it is ensured that the acrylamide is polymerized.

After cooling, the plate is kept at 40C for at least 24 hours allowed to mature. After removal, the gel is immersed in phosphate-buffered saline if necessary with the addition of sodium azide, merthiolate or other additives several times washed to allow unpolymerized material to diffuse out.

Example 2 polyacrylamide (3.5%), agarose (2%) 3.5 g acrylamide and 91 mg of methylenebisacrylamide are dissolved in 50 ml of distilled water. 2 g agarose or agar-agar dissolve in 50 ml of distilled water at 1000C in a water bath brought, allowed to cool to 600C and after adding 60 / kl TEMED and 45 mg peroxydisulfate mixed with the acrylamide solution. The casting of the plate is as in Example 1 described executed. If a tissue-containing gel is desired, the tissue is preferably made of cotton before pouring into the polymerization chamber inserted. The further processing takes place as described.

Example 3 Polyacrylamide (3.5%), Aqarose (2%) and polyethylene glycol (2%) 3.2 g of acrylamide and 82 g of bisacrylamide are dissolved in 30 ml of distilled water solved. In addition, two solutions of 1.8 g each of agar-agar or agarose or polyethylene glycol are used 6000 prepared in 30 ml of distilled water. The agarose becomes in solution at 1000C then all three solutions are kept at 600C. After mixing will be 60 / ul TEMED or a mixture of TEMED and 3-dimethylaminopropiononitrile as well as 45 mg peroxydisulfate added quickly. The casting and further processing of the plate happens as described in Example 1.

Example 4 Polyacrylamide (7.5%), methyl cellulose (5%) 7.5 g of acrylamide and 195 mg of bisacrylamide are dissolved in 50 ml of distilled water and heated to 60.degree warmed up. A second solution is made by dissolving 5 g of methyl cellulose in 50 ml of distilled water, taking care that no lumps remain behind and a homogeneous solution is created. Both solutions are at 600C mixed with one another, the catalysts are added as described in Example 1 and poured the plate in the manner specified there.

It is possible to replace the catalysts with riboflavin, whereby the plate can be exposed to a light source similar to daylight for polymerization got to.

Claims (10)

Claims 1. Transparent liquid dressing material, in particular for the treatment of wounds, characterized in that it consists of a hydrophilic organic transparent gel in sheet or tape form, which with a swollen aqueous solution, the buffer substances, in the wound treatment Can contain customary active ingredients, nutrients and / or growth substances and optionally contains a line-like or net-like arranged reinforcement material. 2. Liquid dressing material according to claim 1, characterized in that that the gel consists of a mixture of hydrophilic polymer and at least one gellable polymer high molecular weight substance. 3. Liquid dressing material according to claim 2, characterized in that that the gel consists of a gellable polysaccharide and / or protein or polypeptide and a polymer of a hydrophilic acrylic or methacrylic acid derivative, which by Polymerization in the presence of the polysaccharide and / or protein or Polypeptide is produced. 4. Liquid dressing material according to claim 3, characterized in that that the hydrophilic acrylic or methacrylic acid derivative has an amide or an ester one optionally containing one or more additional free hydroxyl groups Is alkanol. 5. Liquid dressing material according to claim 3, characterized in that that the polysaccharide is aaarose. 6. liquid dressing material according to claim 3, characterized in that that the protein is gelatin. 7. Liquid dressing material according to one of the preceding claims, characterized in that the gel consists of 10 to 90 percent by weight polymerized Acrylic or methacrylic acid derivative and 90 to 10 percent by weight polysaccharide and / or Protein. 8. Liquid dressing material according to one of the preceding claims, characterized in that it contains up to percent by weight aqueous solution. 9. A method for producing a liquid dressing material according to one of the preceding claims, characterized in that a monomer or Monomer mixture and at least one gellable hydrophilic high molecular substance be dissolved in an aqueous medium as starting materials for the production of the gel1 the solution is given the thickness desired for the sheet or band-shaped material and then the gel formation reaction by adding an inhibitor or an initiator mixture for the polymerization of the polymerizable monomer is started, where appropriate before, during or after the addition of the initiator, a reinforcing material is inserted will. 10. Use of the liquid dressing material according to claim 1 to 8 as a carrier material for cell cultures from which metabolic products are obtained.