TWO-COMPONENT SYSTEM FOR THE THERAPEUTIC TREATMENT OF SKIN LESIONS AND PRODUCTION METHOD THEREOF

Abstract

A two-component system for the therapeutic treatment of skin lesions includes two components. A first component is an aqueous gel. A second component, called cross-linker, is an aqueous solution. The first component includes at least one biocompatible polymer, at least one polyacid or a salt thereof and characterized in that at least one preservative substance, at least one pharmacologically active substance can be present and in that the second component consists of a saline solution including calcium chloride, magnesium chloride and zinc chloride. A method of use involves the prior application of the first component, in the form of aqueous gel in a fluid-viscous state on the skin of a patient, then spraying with the second component as an aqueous solution, causing the formation in situ of a film of rubbery consistency and in that the rubbery film can be removed by washing the skin with water.

Claims

1. Two-component system for the therapeutic treatment of skin lesions, comprising two components, wherein a first component is in aqueous gel form and wherein a second component, called cross-linking agent, is in the form of an aqueous solution, wherein said first component is constituted by at least one biocompatible polymer, by at least one polyacid or one salt thereof and wherein at least one preservative substance can be present as well as at least one pharmacologically active substance and wherein said second component is constituted by a saline solution wherein the cation is bivalent, trivalent or has higher valence.

2. The two-component system according to claim 1, wherein, for the compounds present in the first component, the biocompatible polymer is polyvinyl alcohol with a concentration with respect to said first component between 0.001-30% w/w and in that the compounds present in the first component has a molecular weight comprised in the range between 10 and 1,000,000, wherein the polyacid is represented by polyacrylic acid and by sodium alginate employed on their own or in association, wherein said polyacrylic acid with a molecular weight between 10 and 5,000,000 is present with a concentration with respect to said first component between 0.01-10% w/w and wherein sodium alginate is present with a concentration with respect to said first component comprised between 0-5% w/w with a viscosity ranging between 50 and 2000 cp at 20° C., wherein the antibiotics for dermatological use belong to the aforesaid pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.01-70% w/w, wherein said antibiotics are selected from among the group constituted by metronidazole, metronidazole benzoate, any antibiotic belonging to the family of nitroimidazoles, doxycycline, any antibiotic belonging to the family of tetracyclines, amoxicillin also associated with clavulanic acid and any antibiotic belonging to the family of penicillins, rifaximin and any antibiotic belonging to the family of rifamycins, neomycin, mupyrocin and any combination thereof, wherein antiseptics belong to the aforesaid pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.0001-10% w/w, wherein said antiseptics are selected from among the group comprising chlorhexidine gluconate, iodine, silver ions and any combination thereof, wherein the anti-inflammatory agents belong to the aforesaid pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.001-30% w/w, wherein said anti-inflammatory agents are selected from the group comprising acetylsalicylic acid and/or flurbiprofene and any combination thereof, in wherein tissue regenerative factors belong to the aforesaid pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.001-30% w/w, wherein said tissue regenerative factors are hyaluronic acid, in wherein regenerating factors belong to the aforesaid pharmaceutically active molecules that are selected from among the group comprising hyaluronic acid and/or a sodium salt thereof, retinol, Vitamin A, Vitamin C, Vitamin D, Vitamin E, biotin, linoleic acid, arachidonic acid, co-enzyme Q10, oxygen, oxygenated water, or other compounds developing oxygen and any combination thereof, in wherein local coagulant factors belong to the aforesaid pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.001-4% w/w, wherein said local coagulant factors are selected from among the group comprising Vitamin K, protamine, fibrinogen, prothrombin, calcium, proaccelerin, accelerin, proconvertine, anti-hemophilic A factor, Christmas factor, tissue III factor, Stuart power factor, plasmatic antecedent of thromboplastin, Hageman factor, fibrin stabilizing factor or any one combination thereof and finally wherein the aforesaid preservative compounds are selected from among the group comprising those belonging to the class of parabens or to the group of propyl paraoxybenzoate and methyl paraoxybenzoate or any combination thereof.

3. The two component system according to claim 1, wherein said second component is constituted by a saline solution wherein the cation is bivalent, trivalent or has higher valence, in wherein said salt is selected from the group comprising chlorides, iodides and finally in wherein said salt is selected from the group comprising calcium chloride, magnesium chloride and zinc chloride at the concentration comprised between 0.001 moles and the solution saturation concentration.

4. The two component system according to claim 1, wherein in said first component, at least one fluorescent substance is present for the detection of bacterial strains, such fluorescent substance selected from among the group comprising green fluorescent protein (GFP), fluorescein, dichlorofluorescein, Dylight Fluor, or a combination thereof, and in wherein in said first component, at least one colorimetric indicator is present for the indication of the pH value, of the oxidoreductive characteristics within the gel film, of the salinity, of the oxidoreductive activity and of the dissolved gases and such indicator is selected from among the group comprising bromothymol blue, thymol blue, methyl violet, basic violet 3, methyl yellow, methyl orange, bromophenol blue, bromocresol green, methyl red, phenol red, cresol red, 1-naphtholphthalein, phenolphthalein, thymolphthalein, bromocresol violet, trinitrotoluene, ferroin, N-phenylanthranylic acid, naphthyl black, 2,2′-bipyridine (complex with Ru), nitrophenanthroline (complex with Fe), N-phenylanthranylic acid, 1,10-phenanthroline (complex with Fe), N-ethoxychrisoidine, 2,2′-(complex with Fe), 5,6-dimetylphenanthroline (complex with Fe), o-dianisidine, sodium diphenylaminesulfonate, diphenylbenzidine, diphenylamine, viologen, 2,6-dibromophenol-indophenol, o-cresol-indophenol, thionin (or “Lauth violet”), methylene blue, indigotetrasulfonic acid, indigotrisulfonic acid, carmine indigo (indigosulfonic acid), indigomonosulfonic acid, phenosafranine acid, safranine T, basic red 5, or any combination thereof.

5. The two component system according to claim 1, wherein said system in contact with the skin or mucous membrane acts as a support for at least one device for detecting the temperature, the pH value, the ionic concentration, the saline concentration, the oxygen concentration, the perfusion of oxygen in the tissues, the concentration of carbon dioxide or any combination thereof.

6. A method for the therapeutic treatment of skin lesions in general, as well as wounds, burns, decubitus ulcers and ulcers in animals and humans, comprising administering an effective dose of the two-component system of claim 1 to a patient in need thereof, by applying first component, in the form of an aqueous gel in a viscous-fluid state on the skin of a patient, and subsequently spraying said applied first component with the second component in aqueous solution form, inducing the in situ formation of a film with rubbery consistency, wherein said rubbery film can be removed by washing of the skin with water.

7. The two component system according to claim 1 said film with rubbery consistency, once formed, has a porosity smaller than 10 microns, said film with rubbery consistency has a shear elastic modulus greater than 1,000,000 Newtons per square meter and said film with rubbery consistency has an elongation at break not less than 100%.

8. The two component system according to claim 1, wherein said film performs a bioadhesive activity, in that the bioadhesion process allows the transported active principle to remain in close contact with the site of action or of absorption for a prolonged time period, obtaining an improvement of the pharmacokinetic profile of the active principle itself and in wherein a water-impermeable barrier is attained which prevents the passage of bacteria and spores and which is permeable to gases.

9. The two component system according to claim 1, wherein included among the constituents of the first component are substances for cosmetic use, nutraceutical use and micronutrients.

10. Process for producing and method for applying the two-component system according to claim 1, comprising the stages of: (i) preparing the first component by dissolving, in room-temperature water, polyvinyl alcohol under stirring up to obtaining a uniform solution, then subsequently adding hyaluronic acid, polyacrylic acid, sodium alginate, silver chloride, chlorhexidine gluconate and acetylsalicylic acid; (ii) preparing the second component by dissolving, in room-temperature water, calcium chloride; and wherein said first component is applied on skin lesions and then sprayed with the calcium chloride of the second component by means of a spray nebulizer.

11. The for producing and method for applying the two-component system according to claim 10, wherein said system is used for inserting sensors and comprises the preparation of the base component by dissolving, in room-temperature water, polyvinyl alcohol under stirring up to obtaining a uniform solution, then subsequently adding polyacrylic acid, it too dissolved by means of stirring of the solution, up to obtaining a uniform solution, wherein the temperature and oxygen sensors were inserted and positioned in said final uniform solution, and this was dried in an oven at 40° C. in the presence of dehydrating salt for 24 hours, wherein the final rubbery film containing the sensors was cross-linked at 80° C. for an hour and the solid-elastic film thus obtained is adhered to the skin or mucous membrane above and around the wound or suture, using as adhesive the first component, and then by means of spraying the calcium chloride of the second component is applied by means of a spray nebulizer.

12. The two-component system of claim 1, wherein the biocompatible polymer is polyvinyl alcohol with a concentration with respect to said first component between 1%-10% w/w; the compounds present in the first component has a molecular weight higher than 10,000; said polyacrylic acid with a molecular weight equal to 400,000 is present with a concentration with respect to said first component between 2-4% w/w; sodium alginate is present with a concentration with respect to said first component equal to 1.5% w/w; the antibiotics for dermatological use belong to the pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.5-30% w/w; antiseptics belong to the pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.002-4% w/w; the anti-inflammatory agents belong to the pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.5-10% w/w; tissue regenerative factors belong to the pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.01-2% w/w; and local coagulant factors belong to the pharmaceutically active molecules with a concentration with respect to said first component comprised between 0.2-2% w/w.

13. The two-component system according to claim 2, wherein said second component is constituted by a saline solution wherein the cation is bivalent, trivalent or has higher valence, wherein said salt is selected from the group comprising chlorides, iodides, and wherein said salt is selected from the group comprising calcium chloride, magnesium chloride and zinc chloride at the concentration comprised between 0.001 moles and the solution saturation concentration.

14. The two-component system according to claim 2, wherein in said first component, at least one fluorescent substance is present for the detection of bacterial strains, such fluorescent substance selected from among the group comprising green fluorescent protein (GFP), fluorescein, dichlorofluorescein, Dylight Fluor, or a combination thereof, and wherein in said first component, at least one colorimetric indicator is present for the indication of the pH value, of the oxidoreductive characteristics within the gel film, of the salinity, of the oxidoreductive activity and of the dissolved gases and such indicator is selected from among the group comprising bromothymol blue, thymol blue, methyl violet, basic violet 3, methyl yellow, methyl orange, bromophenol blue, bromocresol green, methyl red, phenol red, cresol red, 1-naphtholphthalein, phenolphthalein, thymolphthalein, bromocresol violet, trinitrotoluene, ferroin, N-phenylanthranylic acid, naphthyl black, 2,2′-bipyridine (complex with Ru), nitrophenanthroline (complex with Fe), N-phenylanthranylic acid, 1,10-phenanthroline (complex with Fe), N-ethoxychrisoidine, 2,2′-(complex with Fe), 5,6-dimetylphenanthroline (complex with Fe), o-dianisidine, sodium diphenylaminesulfonate, diphenylbenzidine, diphenylamine, viologen, 2,6-dibromophenol-indophenol, o-cresol-indophenol, thionin (or “Lauth violet”), methylene blue, indigotetrasulfonic acid, indigotrisulfonic acid, carmine indigo (indigosulfonic acid), indigomonosulfonic acid, phenosafranine acid, safranine T, basic red 5, or any combination thereof.

15. The two-component system according to claim 3, wherein in said first component, at least one fluorescent substance is present for the detection of bacterial strains, such fluorescent substance selected from among the group comprising green fluorescent protein (GFP), fluorescein, dichlorofluorescein, Dylight Fluor, or a combination thereof, and wherein in said first component, at least one colorimetric indicator is present for the indication of the pH value, of the oxidoreductive characteristics within the gel film, of the salinity, of the oxidoreductive activity and of the dissolved gases and such indicator is selected from among the group comprising bromothymol blue, thymol blue, methyl violet, basic violet 3, methyl yellow, methyl orange, bromophenol blue, bromocresol green, methyl red, phenol red, cresol red, 1-naphtholphthalein, phenolphthalein, thymolphthalein, bromocresol violet, trinitrotoluene, ferroin, N-phenylanthranylic acid, naphthyl black, 2,2′-bipyridine (complex with Ru), nitrophenanthroline (complex with Fe), N-phenylanthranylic acid, 1,10-phenanthroline (complex with Fe), N-ethoxychrisoidine, 2,2′-(complex with Fe), 5,6-dimetylphenanthroline (complex with Fe), o-dianisidine, sodium diphenylaminesulfonate, diphenylbenzidine, diphenylamine, viologen, 2,6-dibromophenol-indophenol, o-cresol-indophenol, thionin (or “Lauth violet”), methylene blue, indigotetrasulfonic acid, indigotrisulfonic acid, carmine indigo (indigosulfonic acid), indigomonosulfonic acid, phenosafranine acid, safranine T, basic red 5, or any combination thereof.

16. The two-component system according to claim 2, wherein said system in contact with the skin or mucous membrane acts as a support for at least one device for detecting the temperature, the pH value, the ionic concentration, the saline concentration, the oxygen concentration, the perfusion of oxygen in the tissues, the concentration of carbon dioxide or any combination thereof.

17. The two-component system according to claim 3, wherein said system in contact with the skin or mucous membrane acts as a support for at least one device for detecting the temperature, the pH value, the ionic concentration, the saline concentration, the oxygen concentration, the perfusion of oxygen in the tissues, the concentration of carbon dioxide or any combination thereof.

18. The two-component system according to claim 4, wherein said system in contact with the skin or mucous membrane acts as a support for at least one device for detecting the temperature, the pH value, the ionic concentration, the saline concentration, the oxygen concentration, the perfusion of oxygen in the tissues, the concentration of carbon dioxide or any combination thereof.

19. A method for the therapeutic treatment of skin lesions in general, as well as wounds, burns, decubitus ulcers and ulcers in animals and humans, comprising administering an effective dose of the two-component system of claim 2 to a patient in need thereof, by applying the first component, in the form of an aqueous gel in a viscous-fluid state on the skin of a patient, and subsequently spraying said applied first component with the second component in aqueous solution form, inducing the in situ formation of a film with rubbery consistency, wherein said rubbery film can be removed by washing of the skin with water.

20. A method for the therapeutic treatment of skin lesions in general, as well as wounds, burns, decubitus ulcers and ulcers in animals and humans, comprising administering an effective dose of the two-component system of claim 3 to a patient in need thereof, by applying the first component, in the form of an aqueous gel in a viscous-fluid state on the skin of a patient, and subsequently spraying said applied first component with the second component in aqueous solution form, inducing the in situ formation of a film with rubbery consistency, wherein said rubbery film can be removed by washing of the skin with water.

Description

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] A preferred embodiment of the present invention will now be described in detail also with reference to the production method described below.

[0023] A first aspect of the present invention consists in that said two-component system for the therapeutic treatment of skin lesions as well as wounds, burns, bedsores, ulcers consists of two components, a first component in the form of aqueous gel and a second component in the form of aqueous solution.

[0024] More specifically, said first component is made up of at least one biocompatible polymer, at least one polyacid or a salt thereof and one or more preservative and pharmacologically active substances. The values of the optimal concentration will also be reported below, in order to obtain an effective system capable of guaranteeing the formation of a resistant film, of good elasticity, with adequate porosity for the passage of gases, as well as the oxygen and carbon dioxide but such as to prevent the passage of bacteria.

[0025] In detail, a preferred embodiment of the present invention is characterized in that the biocompatible polymer is polyvinyl alcohol and has a molecular weight in the range of 10 to 1,000,000 and more preferably a molecular weight greater than 10,000, at a concentration with respect to said first component between 0.001-30% w/w and preferably between 1%-10% w/w.

[0026] As far as the polyacid is concerned, this is represented by the polyacrylic acid and sodium alginate taken alone or in association, wherein said polyacrylic acid with a molecular weight between 10 and 5,000,000 and preferably equal to 400,000 is present at a concentration with respect to said first component between 0.01-10% w/w and more preferably between 2-4% w/w and wherein the sodium alginate is present at a concentration with respect to said first component comprised between 0-5% w/w and preferably equal to 1.5% w/w with a viscosity ranging between 50 and 2000 cp at 20° C.

[0027] As far as the pharmaceutically active molecules and the preservatives present in the first inventive compound are concerned, these are manifold and as specified below they belong to various pharmaceutical categories.

[0028] In particular, a preferred embodiment of the present invention provides that the antibiotic for dermatological use is selected from the group consisting of metronidazole, metronidazole benzoate, any antibiotic belonging to the nitroimidazole family, doxycycline, any antibiotic belonging to the tetracycline family, amoxicillin also associated with clavulonic acid and any antibiotic belonging to the penicillin family, rifaximin and any antibiotic belonging to the rifamicin family, neomycin, mupirocin and any combination thereof, at a concentration of the antibiotic with respect to said first component comprised between 0.01-70% w/w and more preferably between 0.5-30% w/w.

[0029] In said preferred embodiment, the antiseptic is selected from the group comprising chlorhexidine gluconate, iodine, silver ions and any combination thereof, at a concentration with respect to said first component comprised between 0.0001-10% w/w, more preferably between 0.002-4% w/w.

[0030] In said preferred embodiment, the anti-inflammatory is selected from the group comprising acetylsalicylic acid and/or flurbiprofen and any combination thereof, at a concentration with respect to said first component comprised between 0.001-30% w/w, more preferably between 0.5-10% w/w.

[0031] In said preferred embodiment, the regenerative factor of the tissues is hyaluronic acid, at a concentration with respect to said first component comprised between 0.001-30% w/w and more preferably between 0.01-2% w/w.

[0032] In said preferred embodiment, the regenerative factor contained in said first component is selected from the group comprising hyaluronic acid and/or a sodium salt thereof, retinol, vitamin A, vitamin C, vitamin D, vitamin E, biotin, linoleic acid, arachidonic acid, co-enzyme Q10, oxygen, hydrogen peroxide, or other oxygen-producing compounds and any combination thereof.

[0033] In said preferred embodiment, the local coagulant factor is selected from the group comprising Vitamin K, protamine, fibrinogen, prothrombin, calcium, proaccelerin, accelerin, proconvertine, anti-hemophilic A factor, Christmas factor, tissue III factor, Stuart power factor, plasmatic antecedent of thromboplastin, Hageman factor, fibrin stabilizing factor or any combination thereof, at a concentration with respect to said first component comprised between 0.001-4% w/w, more preferably between 0.2-2% w/w.

[0034] In said preferred embodiment, the first component contains preservatives selected from the group comprising the members of the paraben class or the group of propyl paroxybenzoate and methyl paroxybenzoate or any combination thereof.

[0035] As regards instead said second component present in the aforementioned preferred embodiment, this is constituted by a saline solution wherein the cation is bivalent, trivalent or has higher valence, wherein said salt is selected from the group comprising chlorides, iodides and wherein preferably said salt is selected from the group comprising calcium chloride, magnesium chloride and zinc chloride at the concentration comprised between 0.001 moles and the solution saturation concentration.

[0036] By way of non-limiting example, a particularly preferred composition according to the present invention is constituted by the presence of the first component in the form of a mixture in aqueous solution of polyvinyl alcohol with a molecular weight of about 90,000 at a concentration of about 2% w/w, of sodium alginate at a concentration of about 2% w/w, of the silver ion at a concentration of about 1% w/w and/or of chlorhexidine gluconate at a concentration of about 2-4% and of flurbiprofen at a concentration of about 5% w/w and consists of the presence of the second component in the form of a saline solution of calcium chloride, with a concentration preferably comprised between 0.001 and 10 M.

[0037] However, although up to now the case has been considered in which pharmaceutically active substances are included among the constituents in the first component, this should not be considered limitative for the present invention, since said inventive therapeutic system can also contain substances for cosmetic, nutraceutical use and micronutrients, in particular to assist tissue regeneration processes. Therefore the fields of application of the release systems of the invention are the medical, pharmaceutical, cosmetic and cosmeceutical (cosmetic for therapeutic purposes) and nutraceutical fields. As already mentioned above, an approach to detecting the dynamic environment of a skin lesion requires the presence at this of chemical, physical or biological sensors, as well as sensors for temperature, pH value, bacterial load value, etc. This situation is implemented by allowing said inventive two-component system to integrate or act as a support for common chemical, physical or biological sensors and indicators as specified below.

[0038] For this purpose, the possibility is envisaged that said inventive system acts as a support for at least one device for detecting the temperature, the pH value, the ionic concentration, the saline concentration, the oxygen concentration, the perfusion of oxygen in the tissues, the concentration of carbon dioxide or any combination thereof.

[0039] Still in the light of the foregoing, the presence is provided, within the composition of said first inventive component of a fluorescent substance for the detection of bacterial strains selected from the group comprising the green fluorescent protein (GFP), fluorescein, dichlorofluorescein, Dylight Fluor, or a combination thereof.

[0040] Another feature within the scope of the concept just described is that said inventive system provides for the presence within the composition of the first component of colorimetric indicators of the state of the skin lesion for the indication of the pH value, of the oxidoreductive characteristics, of the salinity, of the oxidoreductive activity and of the dissolved gases and such indicator is selected from among the group comprising bromothymol blue, thymol blue, methyl violet, basic violet 3, methyl yellow, methyl orange, bromophenol blue, bromocresol green, methyl red, phenol red, cresol red, 1-naphtholphthalein, phenolphthalein, thymolphthalein, bromocresol violet, trinitrotoluene, ferroin, N-phenylanthranylic acid, naphthyl black, 2,2′-bipyridine (complex with Ru), nitrophenanthroline (complex with Fe), N-phenylanthranylic acid, 1,10-phenanthroline (complex with Fe), N-ethoxychrisoidine, 2,2′-(complex with Fe), 5,6-dimetylphenanthroline (complex with Fe), o-dianisidine, sodium diphenylaminesulfonate, diphenylbenzidine, diphenylamine, viologen, 2,6-dibromophenol-indophenol, o-cresol-indophenol, thionin (or “Lauth violet”), methylene blue, indigotetrasulfonic acid, indigotrisulfonic acid, carmine indigo (indigosulfonic acid), indigomonosulfonic acid, phenosafranine acid, safranine T, basic red 5, or any combination thereof.

[0041] In a second aspect, the present invention relates to a method of producing the preferred composition described above. However, the following examples, which relate to the preparation, characterization and use of the product according to the invention, are provided for illustrative purposes only and are not intended to limit in any way the scope of the present invention as defined by the appended claims.

Example 1: Preparation

[0042] The base gel (first component) was obtained by dissolving polyvinyl alcohol, with a molecular weight of 90,000, in water at a concentration of 4% w/w. The solution was stirred until a homogeneous solution was obtained, after which hyaluronic acid was added at a concentration of 0.5% w/w, flurbiprofen at a concentration of 5% w/w and high molecular weight sodium alginate at the concentration of 2% w/w. Finally, silver chloride was added to the whole at a concentration of 1% w/w and chlorhexidine gluconate at a concentration of 2% w/w. The saline solution consists of an aqueous solution of 1 molar calcium chloride.

Example 2: Application

[0043] The gel prepared according to example 1 was applied to skin lesions and then sprayed with calcium chloride prepared according to example 1, by means of a spray nebulizer.

Example 3: Characterization of the Elastic Film

[0044] The rubbery film, obtained with the process described in example 1, is characterized by elasticity and release capacity of flurbiprofen, silver ions, chlorhexidine gluconate and hyaluronic acid contained therein. Measurements of the elastic elongation at break in gel samples were made, which was greater than 100%. The release of flurbiprofen, silver ions and hyaluronic acid was longer than 7 days.

Example 4: Alternative Preparation

[0045] The base gel (first component) was obtained by dissolving polyvinyl alcohol, with a molecular weight of 90,000, in water at a concentration of 4% w/w. The solution was stirred until a homogeneous solution was obtained, after which hyaluronic acid was added at a concentration of 0.5% w/w, polyacrylic acid at a concentration of 0.5% w/w, sodium alginate, with specific viscosity of 4,000 cp, at a concentration of 1.5% w/w. Finally, silver chloride was added to the whole at a concentration of 1% w/w, chlorhexidine gluconate at a concentration of 2% w/w and acetylsalicylic acid at a concentration of 10% w/w.

[0046] The cross-linker (second component) capable of transforming the gel into a solid having the consistency of a soft rubber, consists of an aqueous solution of 1 molar calcium chloride.

Example 5: Alternative Preparation for Inserting Physical Sensors

[0047] The base gel (first component) was obtained by dissolving polyvinyl alcohol, with a molecular weight of 90,000, in water at a concentration of 10% w/w. The solution was stirred until a homogeneous solution was obtained, after which polyacrylic acid was added at a concentration of 4% w/w which was also dissolved by stirring the solution. The final homogeneous solution, after inserting and positioning the temperature and oxygen sensors, was dried in a stove at 40° C. in the presence of dehydrating salt for 24 hours. The final rubbery film containing the sensors was cross-linked at 80° C. for one hour. The solid-elastic film thus obtained is adhered to the skin above and around the wound or suture using as adhesive the gel prepared according to example 1 and applied according to example 2.