FI70140B - TRANSPARENT VAETSKEFOERBANDSMATERIAL - Google Patents

Description

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(51) Kv.lk.4 / lnt.CI.4 a 61 L 15/01 FINLAND — FINLAND (21) Patent application - Patentansöknlng 792030 (22) Application date - Ansöknlngsdag 27 * 06.79 (Fl) (23) Starting date - Glltlghetsdag 27 * 06.79 (41) Become Public - Blivit offentlig 1 6.05 * 80

National Board of Patents and Registration Date of publication and publication

Patent and registration authorities Ansökan utlagd och utl.skriften publlcerad 28.02.86 (32) (33) (31) Pyydetty etuoikeus - Begärd priority 15 * 11 * 78

The Federal Republic of Germany (DE) P 2849570.7 (71) Max-Planck-Gesel1schaft zur Förderung der Wissenschaften e.V.,

Bunsenstrasse 10, 3400 Göttingen, Federal Republic of Germany (72) Herbert Fischer, Burg, Botho Kickhöfen, Freiburg,

The invention relates to a transparent liquid dressing material, in particular for the treatment of wound healing. The invention relates to a transparent liquid dressing material which is intended in particular for the treatment of wound dressings. Eckehard Vaubel, Berlin, Germany 1-Förbundsrepubl iken Tyskland (DE) (74) Berggren Oy Ab

The dressing technique used so far for poorly healing wounds, burns, ulcers, etc. is relatively one-sidedly oriented towards the development of dressings that adapt to the base of the wound and can be easily removed when changing the dressing without causing pain and bleeding.

These Bandages are grease impregnated textiles, partly made of artificial fabrics, partly also made of cotton.

As further development continues, various substances, such as disinfectants or antibiotics, have then been added to these materials.

However, the downside of these materials is that in the case of heavily leaking wounds, the covering is performed with a dressing material which is itself very hydrophobic.

Although the fat in the tissue allows the dressing to be easily removed 70140 2, it covers the wounds relatively tightly with an oily film, so that fluid may remain in the inclusions in the highly secreted wound areas.

Another treatment principle is the use of wet bandages. When these are used, either the wounds covered with gauze pads are flushed with various substances, or - especially in the treatment of skin diseases - dressings are used.

These are associated with two major drawbacks: in the case of occlusive dressings, there is a skin-rotting bulge (as such, it is most often a fluid-saturated compress that is covered with a membrane). When treated with wet dressings, continuous rinsing causes relatively strong evaporative cooling, the beds are only very difficult to keep dry, and thus cause considerable care problems, not to mention the relatively high cost of the equipment that must be used the most during rinsing.

Treatment of exudable and burial wounds should be with hydrophilic materials that are relatively easily removable and should be transparent to detect any recurrent infections that may occur.

To date, the covering and treatment of large-area wounds and ulcers has been done with opaque films, ointments, foams or binders. It has therefore not been possible to visually control the course of healing and detect complications.

In addition, binders often adhere firmly to the wound bed, so there is bleeding and impaired healing associated with dressing replacement. As a result, the use of treatment agents of this quality often results in the formation of scar formations as a consequence.

Also known is a synthetic skin substitute for dressing, which consists of an open-pore, soft polyurethane foam layer and an outer layer with a microporous polytetrafluoroethylene film.

This material is opaque and therefore has the above-mentioned disadvantages due to opacity. In addition, this material is intended to adhere to the wound, so that when the granular tissue is removed, it tears off. The bandage must therefore be changed at short intervals.

3,701 40

A binder material consisting of a liquid polyethylene glycol solvent and a powdered poly (2-hydroxyethyl methacrylate) is further known. The application takes place by dripping and applying a liquid solvent to the wound and sprinkling the polymer powder on it. When using this material, in situ wound preparation is essential; the use of a liquid premix proved unsuitable for the purpose. In terms of type, this is not a binder, but an intermediate form of ointment and liquid-applied wound dressings, which is also associated with the above-mentioned shadows.

The invention is therefore based on the object of obtaining a hydrophobic liquid demo material which is transparent and thus allows monitoring of the underlying parts of the skin, which allows the dressing to be changed without bleeding or other disturbances to healing and which also allows the application of wound healing and healing agents. without having the disadvantages of hitherto wet ties.

DE-OS 27 25 261.5 discloses a transparent liquid dressing material which is particularly suitable for the treatment of wounds, but also for the after-treatment of skin tumors, removal of allergic sensitivities, cosmetic purposes, moisturizing exposed bones and tendons, treatment of dandruff and as a carrier for cell culture and cell culture. hydrophilic, organic, transparent gel swollen in an aqueous solution, which may contain buffers, active ingredients, nutrients and / or growth agents common in wound care, and which may contain a reinforcing material arranged in rows or reticles.

A particular advantage of this dressing is that it is particularly simple to use and can be easily removed or replaced, allows visual inspection of underlying body parts or cell cultures, promotes better wound healing without causing extra granuloma formation, and allows active ingredients to be added through the substance itself.

The high liquid content of this transparent liquid binder material is a downside in terms of storage and storage. Furthermore, the addition of active ingredients and the elimination of secretions take place relatively slowly. It is therefore an object of the present invention, while retaining all the advantages of a transparent liquid dressing material, to provide this in a more easily storable form which allows rapid addition of active ingredients and removal of secretions.

According to the invention, this object is solved by means of a transparent liquid bonding material in the form of a dried clear, swellable film.

The invention therefore relates to a transparent liquid dressing material, in particular for the treatment of wounds, in the form of a dried, swellable clear film made of a hydrophilic organic gel in the form of a sheet or band, which dressing may contain buffers, wound healing agents, nutrients and and / or growth agents and optionally a lined or cross-linked reinforcing material characterized in that the gel is characterized by a swellable agarose and / or gelatin and a polymer made of acrylamide or acrylic ester, the ester moiety of which is derived from an alcohol containing one or more , by polymerization in the presence of agarose and / or gelatin.

The binder material according to the invention is in the form of a very thin glass-clear film which has a very high reversible swelling capacity and which absorbs liquid in a short time, i.e. within about an hour, with 10 times the weight and more re-swelling almost complete later, returning all swollen starting material. mechanical and structural properties. The weight of the dried film is generally 2 to 10%, mainly 3 to 7% by weight of the weight of the swollen moist starting material. The thickness is generally in the range of about 0.5-0.01 mm, mainly 0.3-0.003 mm measured without reinforcement material.

The liquid binder material of the invention can be described as a transparent gel layer after re-swelling, usually in the range of about 0.5 to 10 mm, most preferably in the range of 1 to 5 mm, and in a swollen state in the form of an aqueous solution. The solution contains important substances necessary for the treatment and healing of the wound, such as buffers, antiseptics, antibiotics, active pharmaceutical ingredients, nutrients, growth substances, local anesthetics and the like. All of these agents are known in the context of skin care or wound care and are known to those skilled in the art. Therefore, they do not need to be disclosed in detail here.

To physically reinforce the liquid binder material of the invention, it may contain a reinforcing material enclosed in the gel in the form of a mesh or a row of strands, the individual strands or fibers of which must be positioned so as not to adversely affect the transparency of the material. The reinforcing material is mainly in the form of a large-meshed net. The reinforcing material consists of natural fibers and filaments or man-made fibers and filaments which are neutral with respect to the solution and the actual gel.

The main component of the liquid binder material according to the invention is a hydrophilic, organic, transparent gel consisting of a hydrophilic acrylic acid derivative, i.e. acrylamide or acrylic ester, a polymer prepared and a gel-forming polysaccharide and / or protein, or agarose.

It has been found that particularly advantageous drying and reconstitution properties exist when the polymerized acrylic acid derivative is present in at least the same amounts by weight as agarose and / or gelatin and mainly 60-90% by weight of the total dry matter mass of the gel.

The polymer and the gelling high molecular weight agent, i.e. agarose and / or gelatin, may be in the form of a three-dimensional network formed by the crosslinked polymer and its gelling agent molecules held in pores such as a cage (this structure is obtained by preparing the polymer by crosslinking in the presence of a high molecular weight agent).

70140

As the hydrophilic acrylic acid derivative, an amide or ester with an alkanol is used, in which case, in the latter case, the alkanol residue may additionally have one or more free hydroxyl groups. The alkanol residue usually has 1 to 6 carbon atoms. If no free hydroxyl groups are present, alkanols having 1 to 2 carbon atoms are preferred.

Typical examples of the monomers forming the polymeric component of the gel material are acrylamide, ethyl acrylate, propyl acrylate, butyl acrylate, hydroxyethyl acrylate, hydroxypropyl acrylate acryl acrylate acrylate acrylate acrylic acid, acrylic acid glycine, acrylic acid glycine, Dual and dust functional polymerizable compounds such as methylene bisacrylamide and the like are added as crosslinking agents. These crosslinking agents are known to the person skilled in the art and are therefore not exemplified further here.

Gels are prepared by polymerizing a monomer or monomers in the presence of agarose and / or gelatin in aqueous solution by adding suitable polymerization initiators such as per compounds, for example ammonium persulfate, or by creating the conditions necessary for polycondensation.

The person skilled in the art is well aware of the suitable polymerization conditions and polymerization initiators of the hydrophilic monomers used in each case, so that their listing here can be omitted.

The swelling of the swollen gel sheets obtained as described above is expediently carried out evenly and simultaneously on both sides. In this case, it is necessary to proceed in such a way that, as the drying process progresses, warping, e.g. undulation, is prevented. This is possible according to an embodiment of the method 70140 according to the invention by drying the gel between two porous supports. Suitable support members are, for example, porous synthetic sheets, perforated metal sheets or films and the like. If the porous supports are used as relatively thin films, they are in turn suitable for support by means of a suitable support structure.

According to another embodiment, the wet gel is attached to a row-like or reticulated reinforcing material and dried in this form. The drying itself can be performed at room temperature or higher, under vacuum or at normal pressure. Using the above-described layer structure technique of drying between two porous supports, it was found that a vacuum of up to 1-10 mmHg could be used without adversely affecting the reversibility of the mechanical and structural properties of the wet starting material. If the drying takes place without the use of a vacuum, for example in a warm air stream, mainly metal sheets or films are used as supports for better heat conduction.

Gels with an initial thickness of between 0.5 and about 3 mm proved to be particularly suitable for the drying method.

The best results when using porous supports were obtained with 1-2 mm thick gels, whereby as the thickness increased in this range, better properties were obtained using vacuum than without vacuum. If drying is carried out without the use of a vacuum in a stream of warm air, the best results are obtained with a thickness of 1 mm or less.

The invention provides considerable improvements over the material of DE-OS 27 25 261.5. Thus, the packaging difficulties of the dried conjunctiva and also the keeping sterile are substantially simpler. Second, the moisture-saturated gel already absorbs active ingredients such as antibiotics, anti-cell growth agents, wound hormones, nutrients, local anesthetics and the like only relatively slowly afterwards, because the external substance must exchange with the closed liquid of the gel. In the case of the dry form according to the invention, this exchange is substantially more rapid because the aqueous solution containing the active ingredients is directly absorbed.

Finally, the dry dressing material of the invention is also particularly suitable for use in highly excreted wounds without prior rehydration or only partial rehydration, as it absorbs the excreted exudate to a greater extent than the fully swollen material. In this way, the secretion can be sucked out to the same extent as has been possible with the binder material of DE-OS 27 25 261.5 only through the outlets in this material.

A particularly advantageous property of the dressing material according to the invention in the rehydrated or re-swollen state is that it adheres to a very healthy tissue without, however, sticking at all to the wound itself. This therefore makes it easy to change the bandage when it is necessary.

Due to the translucency or transparency of the material, the course of healing can also be continuously monitored visually. Since the gel is in an aqueous swollen state, in addition, wound treatment and healing agents can be applied without changing the dressing, simply by applying them to the surface of the applied dressing. They then diffuse in dissolved form thus through the upper surface of the underlying skin and are able to act on it.

By selecting the ratio of the acrylic acid derivative to the gelling agarose or gelatin as appropriate, the absorbency and water retention of the binder can be further regulated.

As stated, the binder material according to the invention may itself contain active ingredients. However, the active ingredients which are preferred in each case are only added during or only after the swelling of the dressing, since the treatments are very different and therefore the gel sheet which is not absorbed by the active ingredients can be more easily applied to subsequent treatments 701 40 9. For example, if the re-swollen binder material according to the invention is placed in an iodine-polyvinylpyrrolidone solution, a yellowish-orange discoloration can be observed after only 5 minutes and after 10 minutes a clearly considerable part of the iodine has diffused into the material. Water-miscible solvents such as dimethyl sulfoxide or polyethylene glycols can then be used as carriers.

The material according to the invention remains relatively unchanged at the base of the wound, even in the case of highly excreted wounds, but still dries at the edges, achieving a good adhesion.

When using the dressing material according to the invention, it is primarily protected by a dressing to be placed on top of it, which is most suitably a grease gauze, since this is hydrophobic and retains the liquid in the actual dressing material.

In connection with a reliable method of use, the dressing material according to the invention is applied to the wound so that it can dry out at the edges, then a relatively thick grease-impregnated grease is placed on it, followed by a thin compression bandage and an elastic bandage.

Clinical trials with the dressing material of the invention have shown that it is absolutely tolerable, is ideally simple to use, and allows for trouble-free removal or dressing replacement. A particular advantage is that the wound under the dressing material heals faster without the formation of additional granulomas, which prevents the formation of scar tissue.

The dressing material according to the invention is particularly suitable for the healing of wounds, in particular burns and chronic ulcers. Other applications include post-treatment of skin tumors, removal of allergic sensitivities, cosmetic surgery and the like, keeping exposed bones and tendons moist, neoplasm of susceptible structures such as tendons and free covering membranes, surface anesthesia, dehydration.

In the form of a rod, it can be used to treat bone inflammation, suitably with the addition of tauroline or gentamicin.

It can also be used as a blocking agent in the field of dentistry, e.g. in the form of a cone with a molded wire for extraction.

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

The following examples further illustrate the invention.

Examples 1-6 3.5 g of acrylamide and 91 mg of methylenebisacrylamide are dissolved in 50 ml of distilled water. Dissolve 2 g of agarose or agar in a water bath at 100 ° C in 50 ml of distilled water, allow to cool to 60 ° C, mix, after adding 60 μl of TEMED and 45 mg of peroxydisulphate, acrylamide. with the solution and immediately poured into the polymerization chamber. This is closed with a glass lid so that no air bubbles remain in the closures. The cuvette is kept at 56 ° C for about 30 minutes until it is confirmed that the acrylamide has polymerized. After cooling, the plate is allowed to mature for at least 24 hours at 4 ° C. After removal, the gel is washed several times in phosphate buffered saline, optionally with the addition of sodium azide, mertiolate or other additives to diffuse out the non-polymerized material. If a tissue-containing gel is desired, a woven fabric, mainly made of cotton, is placed in the polymerization chamber before the pulp is cast.

Similarly, five other gels were prepared that differ in the concentrations of Polyacrylamide P and Agarose A. The compositions are given in the following table.

The individual gels were cast into 1-2 mm thick sheets and then placed between porous polyethylene synthetic sheets (manufactured by Firma Pharmacia, Sweden) and dried under vacuum at 2-5 mmHg under vacuum at room temperature. The weight of the obtained films as a percentage of the wet weight of the starting material is also shown in the table.

Re-swelling occurred by immersion in water. The residence time and the degree of re-swelling achieved are also reported in the table.

11,701 40

Table P% 2.5 3.5 5 3.5 3.5 3.5 A% 1 1 1 0.5 1.5 2

Dry weight 3.4 4.8 6.6 3.8 5.4 as a percentage of the wet weight

Re-swelling as a percentage of the initial weight before drying

Time (s) 1,46.7 56.5 50.3 58.5 51.1 55.5 6 54.2 82.9 95.6 81.0 76.5 72.2 24 55.7 84.9 97 , 1 82.3 78.6 74.1

Example 7

Polyacrylamide (5%), gelatin (5%) 5 g of acrylamide and 130 mg of N, N'-methylenebisacrylamide are dissolved in 50 ml of distilled water and the solution is heated to 60 ° C. In addition, 5 g of gelatin are dissolved in 50 ml of hot distilled water and this is also kept at 60 ° C. A 12.5 x 26 cm glass plate with a 2 mm high rim is preheated to 65 ° C with a hot plate. The above solutions are mixed warm while warm, 60 .mu.l of N, N, N ', N1-tetramethylenediamine (TEMED) and 45 mg of ammonium peroxide sulphate are added rapidly, mixed thoroughly and polymerized, washed and dried as described in Example 1.

Example 8

Polyacrylamide (3.5%), agarose (2%) and polyethylene glycol (2%) 3.2 g of acrylamide and 82 g of visacrylamide are dissolved in 30 ml of distilled water. In addition, two solutions of 1.8 g of agar-agar or agarose or polyethylene glycol 6000 in 30 ml of distilled water are prepared. The agarose is dissolved at 100 ° C, after which all three solutions are kept at 60 ° C. After mixing, 60 [mu] l of TEMED or a mixture of TEMED and 3-dimethylaminopropionitrile and 45 mg of peroxydisulphate are added rapidly. Casting and further processing of the sheets are carried out as described in Example 1.

12 7014 0

Example 9 'J 1 n u

Polyacrylamide (7.5%), methylcellulose (5%) 7.5 g of acrylamide and 195 mg of bisacrylamide are dissolved in 50 ml of distilled water and heated to 60 ° C. Prepare a second solution by dissolving 5 g of methylcellulose in 50 ml of distilled water, taking care not to leave lumps and form a homogeneous solution. The solutions are stirred in the invention at 60 ° C, the catalysts are added as described in Example 1 and the plates are cast and dried as mentioned therein.

The catalysts can be replaced by riboflavin, in which case the plate must be exposed to a daylight-like light source for polymerization.

Claims (2)

701 40 13 A transparent liquid dressing material, in particular for wound healing, in the form of a dried, swellable clear film made of a hydrophilic organic gel in the form of a sheet or band, which dressing may contain buffers, active ingredients, nutrients and / or growths for wound care, and optionally lined or cross-linked reinforcing material, characterized in that the gel consists of swellable agarose and / or gelatin and a polymer made of acrylamide or acrylic ester whose ester moiety is derived from an alcohol optionally containing one or more additional free hydroxyl groups by polymerization in the presence of agarose and / or gelatin. Liquid binder material according to Claim 1, characterized in that the gel consists of 50 to 90% by weight of polymerized acrylamide and 5 to 10% by weight of agarose and / or gelatin.