NL7905340A - LIQUID AND TRANSPARENT CONSTRUCTION MATERIAL, THE USES THEREOF, AND A METHOD FOR THE PREPARATION THEREOF. - Google Patents

Description

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Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V. in Gottingen, Federal Republic of Germany

Liquid and transparent dressing material, their use, and an adhesive for their preparation.

For difficult-to-heal finds, burns, crumbs, etc., it has hitherto been developed relatively unilaterally applied dressing material which clings to the find so that it changes easily, without pain and without bleeding, when changed.

Such a dressing material consists of textile impregnated with grease, which is partly of synthetic fiber and partly of cotton. In the course of further development, various substances, such as disinfectants or antibiotics, were added to these materials.

A drawback of such materials, however, is that on very moist wounds a dressing material is applied which itself is highly hydrophobic. The fat in the tissue, while allowing the dressing to peel off easily, covers the found with a greasy film relatively tightly, so that fluid can build up on strongly separating wound surfaces.

15 Their other principle of therapy consists of the application of wet bandages, and this is done either by keeping wounds covered with bandage gauze moist with various liquids, or (and especially in dermatology) by the use of occlusive dressings. There are substantial drawbacks in this regard: in the exclusive-20 dressings, skin softening occurs (such dressings usually consist of a moisture-soaked compress covered with a foil.) In the case of treatment with moist dressings, the continuous wetting leads to a relatively strong evaporative cooling, and the beds are often difficult to keep dry, so that nursing presents major problems, not to mention the relatively high price of the liquids consumed in relatively large quantities.

Treatment of wounds secreting and granulating wounds should be done with a hydrophilic material, which, however, peels off easily and which should be transparent to accommodate any superinfections that may occur.

The covering and treatment of extensive found and ulcers has hitherto been done with opaque membranes, ointments, foams or dressings. A visual check of the course of the healing and timely seeing of complications is therefore not yet possible. In addition, the dressings often become attached to the healing substance, so that changing the dressing is associated with bleeding and interfering with healing. As a result, scar keloids are often obtained as a side effect of such treatment.

Furthermore, a synthetic skin replacement for joints is known, which consists of a layer of soft polyurethane foam with open pores and an outer layer of microporous polytetrafluoroethylene. This material is not transparent and therefore has the associated drawbacks. In addition, this material is designed to stick with the found, so that the granulate is pulled away when it is removed. The dressing must therefore be changed after a very short time.

Furthermore, a dressing material is known which consists of liquid polyethylene glycol (a solvent) and powdered poly (2-hydroxyethyl-20 methacrylate). Application is done by dripping and spreading the liquid onto the wound and then sprinkling the polymer powder on it. With this material, the formation of the coating is essentially on the spot; the use of a liquid premix was found not to be feasible. By its very nature, this is not a bandage material but something that exists between an ointment and a liquid-applied cover film, with the drawbacks already mentioned above.

This invention now provides a hydrophilic, liquid dressing material which is transparent and allows the perception of underlying skin areas, which can be changed without bleeding or other disturbances of healing, and which furthermore allows the simultaneous application of the wound treatment and / or healing makes it possible to use important substances, without the disadvantages that have hitherto occurred with moist dressings.

In German patent application 27 25 261.5 a transparent liquid dressing material is described, which is said to be particularly suitable for the treatment of substances found, but also for the after-treatment of skin cancer, the desensitisation of allergies, for cosmetic purposes, for the maintenance of exposed bones or nerves, for the treatment of psoriasis and as a carrier for cell cultures This consists of a hydrophilic, organic, transparent gel in the form of sheets or tapes, which is already swollen with an aqueous solution is, which solution can contain buffers, finders, nutrients and / or blowers customary for the found treatment, and which optionally still has a filamentous or reticulated reinforcement.

A special advantage of this bandage material is that it is removed in a particularly easy-to-use and trouble-free manner. can be exchanged. Allows visual assessment of the underlying body parts or cell cultures, achieves better wound healing without excessive granuloma formation, and allows the addition of drugs by the material itself.

The high liquid content means a drawback in the storage and maintenance of this transparent, liquid dressing material.

Furthermore, the supply of active ingredients and the removal of separated material are relatively slow. The present invention solves this problem while retaining all the advantages of the transparent liquid dressing material. Compared to German patent application 27 25 261.5, the present invention provides an easier-to-preserve material which makes it easier to remove active substances which have been added and separated. This problem is solved with a transparent liquid dressing material which is presented as a dried, clear, soft film.

The bandage material according to the invention is marketed and stored as a wafer-thin crystal clear film that can swell up very strongly and already within a short time, that is to say within one hour, up to 10 times its weight and even more. can absorb liquid and then recover all the mechanical and structural properties of the swollen starting material. Generally, the weight of the dried film will have from 2 to 10 3, preferably 3 to 7, by weight of the moist, swollen starting material. The thickness is generally between 0.5 and 0.01 mm, preferably between 0.3 and 0.03 mm (measured without any reinforcement).

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The liquid dressing material according to the invention can be described after return sheets having occurred, as a transparent layer of gel which, as usual, has a thickness between 0.5 and 10 mm, preferably between 1 and 5 mm, and is swollen with an aqueous solution. The solution contains substances important for the treatment of the wound and the healing, such as buffers, antiseptics, antibiotics, active medicines, nutrients, boosters, local anesthetics, etc. All these substances are known per se for the treatment of skin and wounds, and need no further explanation here. .

For a physical reinforcement, the bandage material according to the invention may still contain a filamentary or net-like reinforcement, and the individual threads or fibers thereof must be arranged in such a way that the transparency of the material is not substantially reduced by this. Preferably, the reinforcement is in the form of a 5-mesh network. The reinforcement material consists of natural or synthetic fibers or threads which are inert to the solution and the actual gel.

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 a hydrophilic polymer and one or more gellable high molecular substances. The term "polymer" refers here to substances which are produced synthetically from monomers by polymerization (polyaddition or polycondensation). These may be homopolymers or copolymers. The polymer may also be cross-linked by incorporating monomers which contain more than contain groups which are susceptible to addition or condensation, but it is important that the polymer is so hydrophilic that it can swell to slightly transparent in an aqueous medium, on condition that sufficient hydrophilic groups are present in the monomers, for example OH-, NHg - and 30 COOH groups.

In a preferred embodiment, in addition to the polymer defined above, the gel also contains at least one gellable high molecular substance, preferably a high molecular natural material. The gellable carbohydrates and amino acid polymers, as well as combinations and derivatives thereof, are particularly suitable for this.

The polymer and the gellable high molecular weight material 7905340 + 5 may co-exist as a convenient mixture, the constituents being free to move; they may also be in the form of a three-dimensional network consisting of the cross-linked polymer with the large molecules of the gellable substance in its pores, which are then partly retained as cages; such a structure is obtained by causing the polymer to form under cross-linking in the presence of the high-molecular substance. The polymer and the high molecular substance can also be cross-linked by covalent bonds.

Particularly preferably, the hydrophilic organic transparent gel consists on the one hand of a polymer of a hydrophilic acrylic acid or methacrylic acid derivative and on the other hand of at least one gellable polysaccharide and / or polypeptide or protein. It has been found that particularly favorable drying and recovery properties occur when there is at least as much of the polymerized acrylic acid or methacrylic acid derivative as of the gellable substance, and preferably the dry matter of the gel is 60 to 90% by weight. from said polymer.

As an hydrophilic acrylic acid or methacrylic acid derivative, an amide or an ester is particularly preferably used, in the latter case the alkyl radical may have one or more additional free hydroxy groups. Generally, the alkyl or hydroxyalkyl group has 1 to 6 carbon atoms; when there are no free hydroxy groups, alkyl groups with 1 or 2 carbon atoms are preferred. Representative examples of these preferred monomers are acrylamide, methacrylamide, ethyl acrylate, methyl acrylate, propyl acrylate, butyl acrylate and the corresponding methacrylates, hydroxyethyl acrylates, hydroxypropyl acrylate, hydroxybutylacrylate, acrylic acid esters of glycerol, ethyl acrylate, glycerol, ethyl ether, glycerol. As crosslinkers, bi- or polyfunctional polymerizable compounds, such as methyleribisacryl-30 amide and the like, are added. These cross-links are sufficiently known to those skilled in the art and no examples are given.

As a gellable polysaccharide, the gel preferably contains agarose. Other suitable polysaccharides are the pectins, starches, dextrans, polyglycols, cellulose derivatives and agar agar. It is essential for use in the invention that they swell into transparent masses.

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Among the gellable proteins and polypeptides, gelatin is preferred.

The gels are preferably prepared by polymerizing the monomers in the presence of the high molecular weight substance in aqueous solution, by adding suitable polymerization initiators such as per-compounds (eg ammonium persulfate) or by setting conditions necessary for the polycondensation.

The conditions and auxiliaries necessary for polymerization or polycondensation are sufficiently known to the person skilled in the art that they do not have to be listed here.

Drying of the swollen gel plates thus obtained is best carried out evenly and from both sides simultaneously. One must work in such a way that deformation (for example warping) is prevented as drying progresses. This is achieved in a possible embodiment of the method by drying the gel between two porous support bodies. Suitable supporting bodies are, for example, porous sheets of plastic, perforated metal sheets or films, etc.

If relatively thin films are used as supporting bodies, it is effective to support them in turn. In another embodiment of the invention, the wet gel is stretched on a filamentous or reticulated reinforcing material and dried in that form.

The drying itself can take place at room temperature or at an elevated temperature, under vacuum or at ordinary pressure. When using the above-described sandwich technique, i.e. between two porous supporting bodies, it has been determined that a vacuum of 1 to 10 mm can be applied without substantially affecting the properties of the dried sheet with regard to return to the swollen state. If drying is carried out without a vacuum, for example with a stream of warm air, metal plates or films are preferably used for better heat transfer.

Particularly suitable for drying bleaching gels with an initial thickness between 0.5 and 3 mm. In the case of porous support bodies, the best results were obtained with gels from 1 to 2 mm, whereby better properties are obtained with dry under vacuum than without vacuum, 35 especially applies with increasing thickness. Drying without vacuum, with a stream of warm air, gives the best results with an initial thickness of - 790 5 3 40 κ 7 * of 1 mm or less.

Better results are achieved with this invention than with the material according to German patent application 27 25 261.5. For example, the packaging difficulties are now eliminated and it is also considerably easier to keep the material sterile. Furthermore, the gel already saturated with moisture (antibiotics, cytostatics, found hormones, nutrients, local anesthetics, etc.) absorbs only relatively slowly, since this requires an exchange with liquid enclosed in the gel. With the dry form according to the invention this is considerably faster because the active solution containing aqueous solution is directly sucked up.

Finally, the dry dressing material according to the invention can also be used without or with partial rehydration, especially with strongly separating substances, since the separation is then sucked up more strongly than by completely swollen material. In this way it is possible to remove as much secretion as can be achieved with the material according to the D-out patent application 27 25 261.5 only with discharge holes in the material.

A particularly advantageous property of the bandage material according to the invention in the swollen-back state is that it adheres well to healthy tissue but does not stick to the found. This allows for trouble-free change when needed.

Due to the transparency of the material, one can continuously monitor the course of the healing. Moreover, since the gel 25 is in a swollen state, it is continuously possible to apply substances to be used for the cure or the treatment without changing the dressing, by simply applying them on top of the applied dressing. They then diffuse in dissolved form through the bandage to the underlying skin where they can take effect.

Moreover, the choice in ratio between the acrylic acid or methacrylic acid derivative and the gellable polysaccharide or protein makes it possible to control the suction power and the absorption capacity of the dressing material.

As already mentioned, the material according to the invention may already contain carbonizing. Preferably, the desired drugs, etc., are only applied when the bandage swells back or even afterwards, since the therapies vary widely and a gel plate not yet impregnated can more easily be used for different cases if one is used first impregnates during application. For example, if swollen dressing material according to the invention is placed in a solution of iodine and polyvinylpyrrolidone, an orange-yellow color is already visible after 5 minutes, and after 10 minutes an important part of the iodine is apparently diffused into the material. Water-miscible solvents such as dimethyl sulfoxide and the polyethylene glycols can be used as carriers.

The material according to the invention also remains. strongly secreting wounds on the wound itself relatively unchanged, but strong at the edges so that good adhesion is achieved there.

Preferably, when the dressing material according to the invention is used, a covering dressing is applied to protect it, which consists best of fat gauze, which is hydrophobic and which retains the liquid in the actual dressing material.

In a proven manner of application, the dressing material according to the invention is placed on the wound in such a way that it can dry out well on the edges, and then a gauze impregnated with a relatively large amount of fat is placed on top, over which a thin section and finally an elastic ligation.

Clinical trials with the material of the invention have shown that it is absolutely well tolerated, ideally easy to apply, and allows for trouble-free dressing removal and exchange. A particular advantage is that the wound under the dressing material proceeds quickly without excessive granuloma formation, thereby preventing the development of scar keloids.

The dressing material according to the invention is particularly suitable for the healing of wounds, especially of burns and chronic ulcers. Other areas of application include post-treatment of skin cancer, desensitization of allergies, cosmetic procedures and the like, keeping exposed bones and nerves moist, repairing structures threatened by necrosis such as nerves and exposed muscle bundles, local anesthesia and psoriasis (good assessment of releasing the scales is possible).

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In rod form it can be used for the treatment of osteomyelitis, best with the addition of tauroline or gentamycin. It can also be used as tampons in the dentistry, for example in a cone shape with melted wire for drawing out again. Moreover, the material according to the invention can advantageously be used as carriers for cell cultures.

Examples I to VI

3.5 g of acrylamide and 91 mg of methylene bisacrylamide were dissolved in 50 ml of distilled water. 2 g of agarose or agar-agar were dissolved in 50 ml of distilled water on a water bath of 100 ° C.

When cooled to 60 ° C, it was mixed with the 60 µl Temed and U5 mg peroxydisulfate with the acylamide solution, and poured directly into a polymerization chamber. It was covered with a glass lid in such a way that no air bubbles were included. This cuvette was held at 56 ° C for about 30 minutes, until the acrylamide was sure to polymerize. After cooling, the plate was allowed to mature at h ° C for at least another 2 hours. The polymerized slice was now removed from the chamber and washed several times with a phosphate buffered NaCl solution to which sodium azide, merthiolate (or other auxiliaries) were also added. to allow the unpolymerized material to diffuse away (If a reinforced gel is to be added, a fabric, preferably cotton, is placed in the polymerization chamber before the reaction mixture is poured in).

Similarly, five other gels were prepared, distinguishing from the former only in their contents of poly-acrylamide (P) and agarose (A). The compositions thereof are included in the table below.

The individual gels were brought to a thickness of 1 to 2 mm and then placed between two porous plates of polyethylene (from the Swedish company Pharmacia) and dried under a vacuum of 2 to 5 mm of mercury (260-650 Pascal). The table below shows the dry weights as a percent of the starting material, and also to what extent the initial weight was restored upon swelling in water after varying times.

790 5 3 40 10. P <2.5 3.5 5 3.5 3.5 3.5 A% 11 1 0.5 1.5 2

Dry weight 3, 3,8 8, 8 6,6 3,8 5, nit 6,1% initial weight 5% of the starting nitrate achieved during backwelling Time (hours) 1 to 56.5 50.3 58.5 51, 1 55.5 6 5 ^ 2 82.9 95.6 81.0 76.5 72.2

10 2¾ 55.7 8¾, 9 97.1 82.3 78.6 7M

Example VII

5% polyacrylamide, 5% gelatin.

5 g of acrylamide 15 were added to 50 ml of distilled water. and 130 mg of 1, N'-methylenebisacrylamide dissolved, and this solution was heated to 60 ° C. In addition, 5 g of gelatin was dissolved in 50 ml of hot distilled water and also brought to 60 ° C. A 12.5 x 26 cm glass container with a 2 mm high 'rim was previously heated on a warm plate to 65 ° C. Both solutions were mixed hot, and 60 µl of 20 N, N, N ', N' -tetramethylenediamine (1EMED) and mg5 mg of ammonium peroxydisulfate were quickly added and mixed, followed by polymerization, washing and drying in accordance with Example I.

Example VIII

3.5% polyacrylamide. 2% agarose and 2% polyethylene glycol ♦ 3.2 g of acrylamide and 82 mg of bisacrylamide were dissolved in 30 ml of distilled water. In addition, solutions of 1.8 g of agar-agar or agarose in 30 ml of water and of 1.8 g of polyethylene glycol 6000 in 30 ml of distilled water were prepared · After the three solutions, each at 60 ° C, were mixed together, ^Ol ul TEMED and ¾5 mg of ammonium peroxide disulfate added. The polymerization and further work-up of the plate was carried out as described in Example I.

Example IX

7.5% polyacrylamide and 5% methyl cellulose ♦

A solution of 7.5 g of acrylamide and 195 mg of bisacryl-35 amide in 50 ml of distilled water was brought to 60 ° C. A second solution was made up by adding 5 g of methyl cellulose in 50 ml of distilled 790 5 3 40

Claims (11)

Dressing material according to claim 1, characterized in that the film is dried to 2-10% by weight of the swollen starting material. Dressing material according to claim 2, characterized in that the film is dried up to 3-7% by weight of the swollen starting material. U-dressing according to any one of the preceding claims, characterized in that the gel is a mixture of a hydrophilic polyerisate and at least one gellable high molecular weight substance. Dressing material according to claim U, characterized in that. that the gel consists, on the one hand, of a gellable polysaccharide and / or protein and / or polypeptide and, on the other hand, of a polymer of a hydrophilic acetic acid or methacylic acid derivative which has been prepared by polymerization in the presence of the gellable high molecular substance. A dressing material according to claim 5, characterized in that. that the hydrophilic acrylic acid or methacrylic acid derivative is an amide or an ester with optionally one or more additional free hydroxy groups in the alkyl group. Dressing material according to claim 5 or 6, characterized in that the polysaccharide is agarose. Dressing material according to claim 5 'or 6, with the 790 5 3 40' jt. characterized in that the egg protein is gelatin. Dressing material according to one of Claims h to 8, characterized in that the gel is 50 to 90% by weight of an acrylic acid and / or methacrylic acid derivative and 50 to 10% by weight of polysaccharide and / or 5 egg fit is built up. 10. A process for the preparation of dressing material according to any one of the preceding claims, wherein one or more monomers and at least one gellable hydrophilic substance are dissolved in an aqueous medium, this solution is brought to the thickness desired for the sheet or strip-shaped material. and the monomer or monomers is / are polymerized, optionally. a reinforcement is incorporated before or after the polymerization, characterized in that the swollen gel is finally dried. 11. A method according to claim 10, characterized in that the swollen gel is dried from both sides. Method according to claim 11, characterized in that deformation of the egg during drying is prevented. 13. A method according to claim 12, characterized in that the gel is dried between two porous supporting bodies. 20 1U. Method according to claim 10, 11 or 12, characterized in that the gel is dried while being stretched on a wire or net reinforcement. Method according to any one of claims 10 to 1U, characterized in that a swollen gel of 0.5 to 3 mm initial thickness is dried. 16. A method according to any one of claims 10 to 15, characterized in that the drying takes place under vacuum. Use of the material according to any one of claims 1 to 9 as a carrier for cell culture, from which metabolic exchange products are recovered afterwards. 18. Dressing material mainly according to description and / or examples. 790 53 40