CA1116519A - Transparent liquid dressing material, its manufacture and use - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

A transparent liquid dressing material in the form of a sheet or band made of a hydrophilic organic transparent gel swollen with an aqueous solution. The gel may contain active nutrient or growth material. It may contain a thread-like or mesh-like strengthening material. It may be made of a mixture of hydrophilic polymer and a gelable high molecular weight substance.
One specific gel may comprise a gelable polysaccharide and/or protein or polypeptide and a polymer of a hydro-philic acrylic or methacrylic acid derivative obtained by polymerization in the presence of the polysaccharide and/or protein or polypeptide.

Description

The invention is concerned with a liquid dressing material, which is especially useful for treating wounds, with a process for the prod~ction thereof and with the use thereof.
The previous dressing technique in khe case of badly healing wounds, burns, ulcers and the like, has been relatively uniformly oriented towards the development of dressing materials which adapt closely to the base of the wound and, in the case of changing the dressing, can be removed easily, without pain or bleeding.
m ese dressing materials consist of fat-impregnated textiles, partly of synthetic resin fabrics and partly also of cotton.
In the course of further developments, these mate-rials were then admixed with various substances, for example disinfection agents or antibiotics.
Hcwever, it is a disadvantage of these materials that, in the casè of strongly suppurating wounds, a dressing material is applied which is itself very hydrophobic.
The fat in the fabrics ad~ittedly enables a simple pulling off of the dressing but covers the wound with a relatively thick film of fat so that, in the case of highly incised wound surfaces, the retention of fluid can occur.
Another therapeutic principle resides in the use of moist dressings. This takes place either by sprinkling the wounds, which are covered with muslin compresses, with various media or, particularly in dermatology, by the use of occlusive dressings.
In this case, there are two important disadvantages:
in the case of the occlusive dressings, skin macerations occur (they usually consist of a moisture-impregnated compress which is covered with a foil). In the case of a treatment with moist dressinys, the continuous sprinkling leads to a relatively marked col~ness due to evaporation and thus con-siderably nursing problems arise, quite apart from th~
relatively high price of such media which must be used in large amounts for the sprinkling.
A treatment of suppurating and necrosing wounds should take place with hydrophilic media which can be removed relatively çasily and-which, for obser~ation of super-infections which might possibly occur, should be transparent.
~he covering of wounds and ulcerations of large sur-face area previously took place with non-transparent membranes, salves, foams or dressing materials. A visual monitoring of the course of healing and a recognition of complications was, th~refore, no~ possible. Furthermore, the dressing mate-rials frequently stick firmly to the base of the wound SG
that a change of the dressing involves bleeding and a dis-turbance of the course of healing. Therefore, as suhsequent results of such treatment agents, there frequently develop scar keloids.
There is also known a synthetic skin substitute for dressing purposes which consists of an open pored, soft poly-urethane foam layer and an external layer of microporous poly-tetrafluoroethylene film. This material is non-transparent and, therefore, also possesses the above-mentioned disadvant-ages due to the non-transparency. Furthermore, this mate-rial is intended for sticking on to the wounds so that, in the case of pulling it off, the granulations are also pulled away. Consequently, the dressing must be changed frequently.
Furthermore, a dressing material is known which con-sists of a liquid solvent of polyethylene glycol and a poly-(2-hydroxyethyl methacrylate) in powder form. The application t~ces place by dropping the liquid solvent on to the wound and then spread out thereon, whereafter the polymer powder is sprinkled on. In the case of ~his material, the production in situ on the wound i9 importan~, the use of a liquid pre-mixture having proved to be unsuitable. From the whole nature of the material, it is not a dressing material but rather something between a salve and a wound covering film to be applied in liquid form which also suffers from the disadvant-ages already mentioned above~
Therefore, it is an object of the present invention to provide a hydrophilic liquid dressing material which is transparent and, therefore, permits the observation of the parts of the skin lying below it, which permits a change of the dressing without bleeding or o~her disturbances of the course of the healing process and which, in addition, permits the application of materials which are important for the treatment and healing of the wound, without possessing the dis-advantages which have previously arisen in the case of moist dressings.
According to the present invention, this object is achieved by a transparent liquid dressing material which is characterized in that it comprises a hydrophilic, organic, transparent gel in sheet or strip form which is present swollen with an aqueous solution.
In particular the gel comprises at least one gelable high molecular weight substance selected from polysaccharides, proteins and polypeptides, and a polymer of a hydrophilic acrylic or methacrylic acid derivative polymerized in the presence of a gelable high molecular weight substance.
The transparent gel may contain buffer substances, active materi~ls which are conventional for the treatment of . ~

wounds, nutrients and/or growth-promoting materials and optional:Ly also contains therein thread-like or mesh-like streng-thening materials.
The liquid dressing material according to the pre-sent invention can be described as being a transparent gel layer which usually has a thickness of about 0.5 to 10 mm.
and preferably of from 1 to 5 mm. and is present in a state of being swollen with an aqueous solution. The solution contains, in dissolved form, the materials which are important for the treatment and healing of wounds, such as buffer sub-stances, antiseptics, antibiotics, pharmaceutically effective substances, nutrients, growth-promoting materials and the like. All these materials are known and commonplace for the treatrnent of the skin or ~or the treatment of wounds, There-fore, it is here not necessary to describe them in detail.
~' For physical strengthening, the liquid dres~ing material according to the present invention can contain a strengthening or reinforcing material which is incorporated in the gel in the form of threads or mesh and the individual filaments or fibres of which must be arranged in such a manner that the transparency of the material is hereby not substantially impaired. The strengthening material is pre-ferably used in the form of a wide-mesh material. The strengthening material can consist of natural or synthetic filaments or fibres which are inert towards the solution and the actual gel.
The most important component of the liquid dressing material according to the present invention is the hydro-~hilic organic transparent gel. This gel preferably consists of a mixture of the hydrophilic polymer and at least one gel-able high molecular weight substance. By the term '`polymer"

there are here to be understood compounds which have been pro-duced synthetically from monomeric units by polymerization, i.e. by polyaddition or polycondensation. It can ther~by be a homopolymer or a co-polymer of two or more different monomeric units. The polymer can also be cross-linked by the addition of monomers which con-tain more than one group capable of addition or condensation. Ilowever, it is important that the polymer is so hydrophilic that it is able to gel trans-parently in an aqueous medium. A prerequisite for this is that in the monomeric units there are present sufficient numbers of hydrophilic groups, for example hydroxyl groups, primary amino groups, carboxylic acid groups and the like.
The gelabla high molecular weight substance is preferably a high molecular weight natural substanceO Among these, particularly suitable substances include the gelable carbohydrates and the gelable polyamino-acids, as well as -~combinations and derivatives thereof.
The polymer and the gelable high molecular weight substance can be present as ordinary mixtures with one another in which the components are freely moveable.
However, thay can also be in the ~orm of a three-dimensional meshwork which consists of cross-linked polymer and, in the pores thereof, the molecules of the gelable high molecular weight substances are firmly held as in a cageO This structure is obtained by producing the polymer with cross-linking in the presence of the high molecular weight sub-stance. Alternatively, the polymer and the high molecular weight substance can also be joined together by covalent bonds.
The hydrophilic organic transparent gel is especially preferably composed of a polymer of a hydrophilic acrylic acid or methacrylic acid derivative and at least one gelable polysaccharide and/or protein or polypeptide.

~ 5 --The hydrophilic acrylic or methacrylic acid derivative i9 especially preferably an amide or an ester with an alkanol, whereby, in the latter case, the alkanol residue can additionally also contain one or more free hydroxyl groups.
The alkanol residue generally contains up to 6 carbon atoms.
If no free hydroxyl groups are present therein, then alkanols with 1 to 2 carbon atoms are preferred.
Typical examples for this preferred group of monomers for the polymerisation components of the gel material include acrylamide, methacrylamide, ethyl acrylate, methyl acrylate, propyl acrylate, butyl acrylate and the corresponding meth-acrylates, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxybutyl acrylate and the corresponding methacrylates, acrylic acid glycerol ester, acrylic acid erythritol ester, acrylic acid pentaerythritol ester and the corresponding methacrylic acid compounds. As cross-linking agents there can be used bi- or polyfunctional, polymerisable compounds, such as methylene-bisacrylamide and the like. These cross-linking agents are well known and do not need to be further exemplified here.
As gellable polysaccharide, the gel preferably con-tains agarose. Examples of other polysaccharides which can be used include pectin, starch, dextran, polyglycols, cellulose derivatives and agar-agar. The gelability is important for suitability according to the present invention, i.e. trans-parent masses must be formed in a swollen state.
Amongst the gelable proteins and polypeptides, gelatine is preferred.
The production of the gels preferably taXes place by polymerization of the monomer or monomers for the polymer compon~nt in the presence of the high molecular weight sub-!~

~65i~L~

stance in aqueous solution by the addition of appropriate polymerisation initiators, such as per compounds, for example ammonium persulphate, or with the provision of the conditions necessary for poly~ondensation.
In accordance with another aspect of the invention there is provided a process for t:he production of the liquid dressing material of the invention which compxises: dis-solving in an aqueous medium a polymerizable monomer or monomer mixture to form the polymer of the hydrophilic acrylic or methac-rylic acid deri~ative, and the at least one gelable high molecular weight substance to form a solution effective to provide a desired thickness for the sheet or strip material, and initiating gel-formation by addition of at least one initiator for the polymerization of the poly-merizable monomers.
The appropriate polymerisation conditions and poly-merisation initiators for use in connection with particular monomers are well known so that it is here unnecessary to describe them in detail.
In yet another aspect of the invention there i 5 pro-vided an improved method of culturing cells for the pro-duction of metabolic products, in a culture medium containing a substrate, in which the substrate is the liquid dressing material of the invention.
The dressing material according to the present invention is always present in a state swollen by aqueous liquids. A temporary dehydration between production and use of the dressing material should not take place since the outstandingly favourable properties of the material cannot be completely obta~ned again. The material is preferably packed into sterile packings in its final swollen state and can then be used directly simply by opening the packings. The content of a~ueous liquid i9 preferably from 15 to ~0% ~y weight.
An especially advantageous and surprising property of the dressing material according to the present invention is that it adheres well to healthy tissues, whereas it does not stick to the wound itself. Therefore, this permits a problem-free changing of the dressing when this is necessary.
As a result of the transparency of the material, the course of healing can be visually continuously monitored.
Since the gel is present in an aqueous swollen state, it is, furthermore, possible, to apply materials needed for treat ing or healing the wounds without changing the dressing merely by applying these materials to the dressing on the wound. They then diffuse in dissolved form through the dressing to the underlying skin surface and can there exert their beneficial influence.
Furthermore, by choice of the ratio of acrylic or methacrylic acid derivative to the gelable polysaccharide or protein, the absorbency and water retention of the dress-ing material can be re~ulated.
~ he dressing material according to the present invention is, after production thereof, placed in moisture-proof packings of synthetic resin or metal or the-like, for Pxample is sealed between synthetic resin foils, metal foils or in metal containers in order to prevent a drying out. ~hus, for example, the dressing material is sealed in foils and several such packed dressing sheets are, in turn, packed into a synthetic resin or metal container which, shortly before application to a wound can then be used simultaneously for the production of the bath for the dressing sheets.

As already mentioned, the dressing material accord-ing to the present invention can already contain active mate-rials dissolved therein. However, the particular desired active materials are preferably applied shortly before the application of the dressing or only thereafter since the therapies can vary very considerably and, therefore, a gel plate which is not impregnated with active materials can more easily be adapted to the various forms of therapy by subsequent impregnation. If, for example, a dressing mate rial according to the present invention is placed in an iodine-polyvidone solution, then after only 5 minutes a yellowish-orange colour can be seen and after 10 minutes it is apparent that a considerable part of the iodine has diffused into the material. Water-miscible solvents, such as dimethyl sulphoxide or polyethylene glycols, can thereby be ~sed as carriers.
The dressing material according to the present invention lies relatively unchanged on the base of the wound, even in the case of strongly suppurating wounds but, never-theless, dries hard on the edges so that from there a goodhold is achieved.
In the case of the use of the dressing material according to the present invention, in order to protect it, it is preferable to apply another dressing on top of it which preferably consists of a fatty gauze since this is `
hydrophobic and retains the liquid which is present in the actual dressing.
In ithe case of one method of use which has proved to be particularly useful, the dressing material according to the present invention is applied to the wound in such a manner that it can dry hard on the edges,!then a relatively highly fat-impr~gnated fat gauze is pla~ed thereon, followed by a thinner compress dressing and an elastic binding.
Clinical trials with ~he dressing material according to the present invention showed that it i9 absolutely compatible, is extremely simple to employ and permits a trouble-free removal or change o~ dressing. It is a particular advantage that the wound healing underneath the dressing material takes place vey quickly without excessive granuloma formation which avoidsthe formation of scar keloids.
The dressing material according to the present invention is especially suitable for the healing of wounds, particularly of burn wounds and chronic ulcerations. Other fields of use include the subsequent treatment of skin tumors, desensitisation of allergies, cosmetic operations and the like, keeping moist exposed bones and tendons, as well as for the treatment of psoriasis, a good observation of the removal of epithelial tissue being possible.
The ~ollowing Examples are given ~or the purpose of illustrating the present invention:
Example 1 Poly~rylamide (5%?, ~elatine (5/O) 5 g. Acrylamide and 130 mg. ~,N'-methylene-bis-acrylamide are dissolved in 50 ml. distilled water and the solution heated to 60C~ Furthermore, 5 g. gelatine are dissolved in 50 ml. hot distilled water and also kept at 60C. A glass plate with the dimensions 12.5 x 26 cm., with a 2 mm. high edge, is pre-heated to 65C. on a hot plate. The two above-mentioned solutions are mixed while warm, 60 ~ ,N,~',N'-tetramethylenediamine (TEMED) and 45 mg. ammonium peroxide disulphate rapidly added thereto, mixed up and immediately poured into the polymerisation chamber. This is closed with a glass cover in such a manner that no air bubbles are enclosed. The cuvette is then kept for about 30 mlnutes at 56C. until it is ensured that the acrylamide has polymerised. After cooling, the plate is left to ripen for atleast 24 hours at 4C. After removal, the gel is washed several times in phosphate-bufferred sodium chloride solution, optionally with the addition of sodium azide, merthiolate or one or more other additives, in order to permit non-polymerised material to diffuse out.
Example 2.
Polyacrylamide ~3.5%), a~arose (2%).
3.5 g. Acrylamide and 91 mg. methylene-bis-acryl-amide are dissolved in 50 ml. distilled water. 2 g. Agarose or agar-agar are brought to ^solution in 50 ml. distilled water at 100C. in a water-bath, àllowed to cool to 60C.
and, after the addition of 60 ~1. T~ME`D* and 45 mg. ammonium peroxide disulphate, mixed with the acrylamide solution.
A plate is cast therefrom in the manner described in Example 1. If a fabric~containing gel is desired, then the fabric, preferably of cotton, is placed in the poly-merisation chamber before pouring in the polymerisation mixture for casting. Further working up is carried out as described hereinbefore.

* trade mark Example 3.
Polyacrylamide (3.s%?, a~arose (2%) and polyethYlene qlycol (2%).
3.2 g. Acrylamide and 82 g. bisacrylamide are dissolved in 30 ml. distilled water. Furthermore, two solutions are prepared each of 1.8 g. agar-agar or agarose and of polyethylene glycol 6000 in 30 ml. distilled water.
The agarose is brought into solution at 100C., where-after all three solutions are kept at 60C. After mixing, 60 ~1. TEMED* or a mixture of TEMED* and 3-dimethyl-aminopropionitrile, as well as 45 mg., ammonium peroxide disulphate, are quickly added thereto. The casting and further working up of the plate is carried out in the " manner described in Example 1.
Exam~le 4.
Polyacrylamide (7.5~), methy~ cellulose (5~/O).
7.S g. Acrylamide and 195 mg. bisacrylamide are dissolved in 50 ml. distilled water and heated to 60C.
A second solution is prepared by dissolving 5 g. methyl cellulose in 50 ml. distilled water, taking care that no lumps remain behind and a homogeneous solution is ~ormed.
Both solutions are mixed together at 60C., the catalysts are added as described in Example 1 and the plate is cast in the manner described therein.
It is possible to replace the catalysts by ribo-flavin, in which case, for polymerisation, the plate must be exposed to a source of light similar to daylight.

* trademark 5~

In addition to being used as wound dressings, the materials according to the present invention can also be used for various other purposes. Thus, for example, they can be used as a gubstrate for cell cultures from which metabolic product~ can subse~uently be obtained.

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Claims (12)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A transparent liquid dressing material which is especially useful for the treatment of wounds, comprising a hydrophilic organic transparent gel in the form of a sheet or strip, swollen with an aqueous solution, said gel comprising:
a) at least one gelable high molecular weight substance selected from the group consisting of polysaccharides, proteins and polypeptides; and b) a polymer of a hydrophilic acrylic or methacrylic acid derivative polymerized in the presence of component a).

2. A dressing material according to claim 1, wherein there is present in the aqueous solution at least one sub-stance selected from conventional active materials, nutrient materials and growth materials.

3. A dressing material according to claim 1 or 2, wherein the gel contains a thread-like or mesh-like strengthening material.

4. A dressing material according to claim 1, wherein the hydrophilic acrylic or methacrylic acid derivative is an amide or an ester with an alkanol.

5. A dressing material according to claim 4, wherein said derivative contains one or more free hydroxyl groups.

6. A dressing material according to claim 1, 2 or 4, wherein component a) comprises agarose.

7. A dressing material according to claim 1, 2 or 4, wherein component a) comprises gelatine.

8. A dressing material according to claim 1, wherein the gel contains 10 to 90%, by weight, of component b) and 90 to 10% by weight of at least one of a polysaccharide and a protein.

9. A dressing material according to claim 1, 4 or 8, wherein said aqueous solution is present in an amount of 15 to 90%, by weight.

10. A process for the production of a liquid dressing material comprising a hydrophilic organic transparent gel in the form of a sheet or strip, swollen with an aqueous solution, said gel comprising:
a) at least one gelable high molecular weight substance selected from the group consisting of polysaccharides, proteins and polypeptides; and b) a polymer of a hydrophilic acrylic or methacrylic acid derivative polymerized in the presence of component a), which process comprises:
i) dissolving in an aqueous medium a poly-merizable monomer or monomer mixture to form said polymer b) and said at least one gelable high molecular weight substance to form a solution effective to provide a desired thickness for the sheet or strip material, and ii) initiating gel-formation by addition of at least one initiator for the poly-merization of the polymerisable monomers.

11. A process according to claim 10, wherein a strengthening material is introduced before, during or after the addition of the initiator.

12. In a method of culturing cells for the production of metabolic products, in a culture medium containing a substrate, the improvement wherein said substrate is a mate-rial as defined in claim 1 or 4.