IT201900002767A1 - MEDICAL DEVICE FOR THE TREATMENT OF SKIN DISEASES AND RELATIVE METHOD OF IMPLEMENTATION - Google Patents

Description

Description of the invention having as title:

"MEDICAL DEVICE FOR THE TREATMENT OF SKIN DISEASES AND RELATIVE METHOD OF IMPLEMENTATION"

FIELD OF APPLICATION

The present invention refers to a medical device for the treatment of skin diseases and to a method for the realization of the medical device, generally usable to treat skin lacerations avoiding the onset of microbial infections even resistant to conventional drugs.

STATE OF THE TECHNIQUE

Medical aids are known, typically in the form of gauze or gauze compresses, used in the treatment of skin diseases, such as, for example, lacerations, wounds, burns.

In particular, the gauze used falls within the type of medical device defined as pre-medicated, i.e. they are prepared for use by soaking them with one or more drugs that have a disinfectant, pain-soothing and regenerative effect on damaged skin tissues when applied to the area. of the lesion, or in the so-called "bed" of the lesion.

The substances used for the preparation of these pre-medicated gauze typically include small percentages of natural antimicrobials, such as, for example, essential or synthetic oils (for example, the "Bunshield" or "Buncare" gauze) with which they are soaked. gauze before use.

Other pre-medicated gauzes use a hydrogel that allows the area of the lesion to be kept moist and to promote autolytic "debridement" or debridement, granulation and epithelialization.

This type of gauze has some technical drawbacks.

A first drawback consists in the fact that due to the use of a hydrogel for the preparation of pre-medicated gauze, the latter can become occlusive and, due to water saturation, the absorption of exudate is limited, favoring, as a consequence , microbial proliferation.

A further drawback consists in the fact that, in general, since wounds are a fertile ground for the establishment of infectious processes that can compromise wound healing and the health of patients, it is necessary to provide for the application of secondary dressings, meaning with this term a dressing with the function of filling the injured cavity or fixing the primary dressing, aimed at avoiding, or at least limiting, these risks.

Another drawback consists in the fact that the treatments for the treatment of skin lesions performed using known pre-medicated gauzes produce skin maceration processes and the development of bad odors.

Another drawback is that the pre-medicated gauze that uses small percentages of natural or synthetic antimicrobial agents do not always have specifically hydrophilic characteristics, making it difficult to be compatible with the hydrogel.

There is therefore the need to provide a medical device capable of overcoming at least one of the drawbacks of the known art.

The purpose of the present invention is therefore to make available a medical device for the treatment of skin diseases that allows to medicate the injured skin surface, to avoid the adhesion of the device to the wounds, to promote the immune response of patients, to avoid over- microbial infections even resistant to conventional drugs. Another object of the present invention is to provide a medical device for the treatment of skin diseases which allows to use a medicament in substitution of essential or synthetic oils with another substance that is hydrophilic and economical, coming from waste from production processes. production of essential oils.

A further object of the present invention is to provide a method for making the medical device which is simple and economical. To obviate the drawbacks of the known art and to obtain these further objects and advantages, the Applicant has studied, tested and implemented the present invention.

EXPOSURE OF THE FOUND

The present invention is expressed and characterized in the independent claims. The dependent claims disclose other features of the present invention or variants of the main solution idea.

According to an aspect of the present invention, a medical device is provided for the treatment of skin diseases, comprising a support for skin application, and a medicament associated with the support and intended to be placed in contact with an injured area of the skin.

According to a characteristic aspect of the present invention, the medicament comprises a hydrogel having the following composition: gellan gum gel, calcium acetate, hydrophilic hydrolate of Citrus aurantium flowers, preservatives for topical human use.

According to an embodiment of the present invention, the gellan gum gel is comprised between 1% and 3% by volume with respect to a total volume of the hydrogel.

According to an embodiment of the present invention, the calcium acetate is between 0.03% and 0.05% by volume with respect to a total volume of the hydrogel.

According to an embodiment of the present invention, the hydrophilic hydrolate of Citrus aurantium flowers is between 45% and 55% by volume with respect to a total volume of the hydrogel.

According to an embodiment of the present invention, the preservatives for topical human use are used in a mixture with a concentration between 0.15% and 0.35% by volume with respect to a total volume of the hydrogel.

In one embodiment, the preservatives are compounds known in the art for which the relevant bodies have authorized their use for human topical use. By way of example they may comprise 0.35% phenoxyethanol, 0.1% benzoic acid, 0.05% dehydroacetic acid. The experimental tests carried out, described in detail below, have shown that the introduction of preservatives, which alone at the final concentrations tested do not show any antibacterial or antimicrobial action, allows to enhance the antimicrobial action of the hydrolate, as well as guaranteeing the correct storage of the same at least until the expected expiration date.

According to an embodiment of the present invention, the hydrogel is in the solid state.

According to an embodiment of the present invention, the support for skin application is a fabric gauze.

According to alternative embodiments, the support is configured as a suitable vehicle intended to ensure a cutaneous application of the drug. In these embodiments, the vehicle, that is the inactive basic substance which allows the administration and therefore the use of the medicament, and, in some cases, also regulates its release on the site of action, can for example be a cream or a ointment.

According to an embodiment of the present invention, the hydrophilic hydrosol of Citrus aurantium flowers comprises hydrophilic hydrolat of Citrus aurantium flowers in the amara variant.

According to another aspect of the invention, a method is provided for the production of a medicament which can be associated with a support for skin application which provides for creating a volume of hydrogel by dissolving a second quantity of gellan gum powder in a first quantity of water, by means of heating to a temperature higher than 40 ° C.

According to a characteristic aspect of the method according to the present invention, a third quantity of hydrophilic hydrosol of Citrus aurantium flowers is added to the volume of hydrogel, in which this step of adding the hydrosol requires that the aforementioned addition takes place by stirring the first step and in the cooling phase.

According to an embodiment, the first and second quantities form a solution that has a volume equal to 50% of the final volume of the hydrogel.

According to one embodiment, the third quantity has a volume equal to 50% of the final volume of the hydrogel.

According to an embodiment, the cooling takes place at a temperature below 40 ° C.

According to another aspect of the present invention, the use of hydrophilic hydrosol of Citrus aurantium flowers is envisaged, in particular in its bitter variant, for the treatment of skin diseases.

Advantageously, the medical device according to the present invention avoids the proliferation of pathogenic microorganisms in skin lesions, and at the same time stimulates the local immune response of the patients, thus accelerating their healing.

An advantage of the medical device according to the present invention is to counteract the development of bad odor due to the skin maceration process which often occurs in the presence of lesions and / or burns, thanks to the presence of the hydrolate of Citrus aurantium flowers.

The medical device according to the invention can be made in the form of hydrogel with which to soak gauze or compresses (or other similar supports). Advantageously, thanks to the hydrophilic nature of the hydrosol of Citrus aurantium flowers, it is easily miscible with the hydrogel. The result is a method of producing the drug which is economical and effective.

In all cases, the packages containing the pre-medicated gauze must be placed on the market in packages designed to preserve their sterility and prevent dehydration, which can also be stored at room temperature without deteriorating the medical device.

The medical device according to the invention, for example in the form of pre-medicated gauze, is able to prevent the development of microbial infections by exerting a cytocidal action on a broad spectrum of microbial species generally involved in human skin infections.

This allows for better management of the injury.

The prevention of infections together with the attenuation of aggressive pro-inflammatory responses, allows the healing process to be completed in a short time without resorting to local or oral antimicrobial therapies that weaken the patient and contribute to the development of antibiotic resistance.

Finally, the specific syneresis of the hydrogels allows the gradual release over time of the active ingredients contained in it and therefore a continuous and gradual treatment of the injured skin area.

Through a dressing, the patient can recover quickly by reducing the period of convalescence and avoiding health costs related to the development of infected wounds.

Another advantage of the medical device according to the present invention is that of being ecological given the presence of the hydrosol of Citrus aurantium flowers, which is in fact a vegetable product obtained as a waste product during the manufacturing process of the corresponding essential oil of Citrus aurantium, in particular in its bitter variant.

These and other aspects, features and advantages of the present disclosure will be better understood with reference to the following description, the drawing tables and the attached claims. The drawing tables, which are integrated and forming part of the present description, illustrate some embodiments of the present object and, together with the description, aim to describe the principles of disclosure.

The various aspects and features described in the present disclosure can be applied individually where possible. These individual aspects, for example aspects and characteristics present in the description or in the attached dependent claims, can be the subject of divisional questions.

It should be noted that any aspect or characteristic that is found to be already known during the patenting procedure is intended not to be claimed and to be the subject of a disclaimer.

ILLUSTRATION OF DRAWINGS

These and other characteristics of the present invention will become clear from the following description of embodiments, given by way of non-limiting example, with reference to the attached drawings in which: - fig. 1 is a histogram showing the results of cytotoxicity tests conducted on gingival fibroblast cells treated with substances released within 24 hours from hydrogels formulated with 50% of Citrus aurantium variant amara (a) flower hydrosol or hydrosol obtained from flowering tops of Monarda fistulosa (b);

- fig. 2 a) is a graph showing the superposition of chromatograms for gellan with hydrosol of Citrus aurantium variant amara flowers at different times; 1h, 3h (diluted 1:10), 6h, 24h, 30h (diluted 1: 5).

- fig. 2 b) is a graph showing the superposition of chromatograms for gellan with hydrosol of Monarda fistulosa MF at different times; 1h, 3h, 6h (diluted 1: 3).

- fig. 3 shows a histogram illustrating the release of carvacrol from gellan made with Monarda fistulosa hydrosol.

To facilitate understanding, identical reference numbers have been used wherever possible to identify identical common elements in the figures. It should be understood that elements and features of one embodiment can be conveniently incorporated into other embodiments without further specification.

DESCRIPTION OF EMBODIMENTS

Embodiments described herein refer to a data processing method, some particular embodiments of which will be described below, by way of non-limiting example.

Example 1: STUDY OF THE INHIBIT AND CYTOCIDAL ACTION OF SOME HYDROLATES ON CLINICAL MICROBIAL STRAINS AND ATCC STRAINS (acronym of the English "American Type Culture Collection") The purpose of this study was to identify the most effective antimicrobial hydrolates as cytocidal activity among some chosen.

The activity of the hydrolates was tested against clinical isolates and ATCC reference strains, sensitive and resistant to antibiotics. Specifically, both fungal strains and GRAM + and GRAM- bacterial strains were studied, most responsible for skin infections in humans.

To achieve this goal, 11 clinical strains were studied {Candida albicans, C. parapsilosis, C. glabrata, Pichia sp, Staphyloccoccus aureus, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, S. aureus MRSA, E. faecalis VRE) and 10 ATCC strains (C albicans 24433, C. parapsilosis 22019, C. krusei 6258, S. aureus MS SA 29213, E. faecalis 29212, Pseudomonas aeruginosa 27853, S. aureus MRSA 43300, S. aureus 25923).

By means of an in vitro dilution micro-broth test, performed in 96-well plates and according to international EUCAST guidelines, the cytocidal capacity of the following hydrolates was tested: Monarda citriodora, Monarda fistulosa, Monarda didyma, Lavandula vera, Citrus aurantium variant amara from flowers, the latter marketed by Magentina srl.

Scalar dilutions between 1/2 v / v and 1/32 v / v were tested for all hydrolates.

The efficacy values were expressed in terms of Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal or Bactericidal Concentration (respectively, MFC or MBC), both identified respectively in the lower concentration of hydrolate present in the well capable of inhibiting microbial growth or have a cytocidal effect with a visible absence of turbidity (microbial growth index) of the medium.

The MIC values were identified by visualization and confirmed with OD reading (450 nm) on the spectrophotometer, while the values of the cytocidal concentrations were identified by sowing the contents of the wells on suitable nutrient medium (Sabouraud for fungi and Mueller Hinton for bacteria ) and reading the sowing result after 24h of incubation.

The data obtained from these first analyzes are summarized in Table 1.

Table 1

The most effective hydrosol in vitro was that of Citrus aurantium variant amara. The others, while showing efficacy, appear to be active at higher concentrations.

The hydrosol of Citrus aurantium variant amara was more active on fungal strains than on bacterial ones.

Among the latter, only E. faecalis - both the clinical strain and the ATCC strain - showed greater resistance to cytocidal action while remaining strongly inhibited in growth at the lowest concentrations tested (1/32).

In light of the results obtained, it is evident that the hydrolate of Citrus aurantium variant amara was the most effective in terms of cytocidal action.

Example 2: IN-DEPTH STUDY OF EFFECTIVENESS

OF CITRUS HYDROLATE A URANTIUM AMARA VARIANT.

The objective of the study is to analyze the effective inhibitory and cytocidal efficacy of the hydrosol of Citrus aurantium variant amara.

This goal was outlined in consideration of the fact that the product featured on the label the addition of legally compliant preservatives to increase the shelf-life of the product.

To perform the study, a pure sampling of Citrus aurantium variant amara hydrosol only was required.

The industry at the time of production provided both the hydrosol with the addition of preservatives, and the one as it is, both coming from the same collection.

The micro-broth dilution analyzes were repeated on the different microbial strains and according to the method indicated in Example 1 by testing, in parallel with the hydrolates, the mixture of preservatives in the proportions used for the formulation.

In table 2 below, the results of the study of the cytocidal action of the hydrolate of Citrus aurantium variant amara alone, of the mixture of preservatives alone and of the two combined together have been introduced. Table 2

In the table, the abbreviation CC indicates "with preservative", the abbreviation SC indicates "without preservative", and the abbreviation C indicates only the "preservative". The results obtained show that the preservative alone, at the concentrations tested in the micro broth-dilution assay, is not able to inhibit the microbial growth, nor to kill, the tested strains.

The hydrolate of Citrus aurantium variant amara alone is effective at higher concentrations than those identified in the combination of hydrolate and preservatives.

In the formulation, the action of the hydrolate is enhanced by the presence of preservatives, this indicates a synergy between the hydrosol and the preservatives when combined in the final formulation.

Example 3: STUDY OF THE TERPENIC COMPONENTS OF

HYDROLATES OF CITRUS AURANTIUM AMARA VARIANT AND OF

MONARDA FISTULOSA.

The aim of the study was to identify the terpene components of the hydrolates of Citrus auratium variant amara and of Monarda fistolosa. A liquid-liquid extraction was performed by mixing an amount of 0.5 ml of hydrolates with 0.5 ml of heptane with tridecane as an internal standard.

A mixer (Retsch-MM300, Haan, Germany) was used for 1 hour at 4 cycles per second.

Supenatants were used for analysis after centrifugation at 4000 rpm for 10 minutes at 10 ° C in an Eppendorf mod. 581 OR (Westbury, NY).

The heptane extracts were then filtered with 0.45 µm PTFE syringe filters and injected (3 µΐ) into Agilent Tech's GC-MS system (Palo Alto, AC, USA).

An Agilent 7820 GC chromatograph equipped with a 5977A MSD mass spectrometer with EI ionization operating at 70 eV was used for analysis.

A J&W Innovax 50 m, 0.20 mm, ID 0.4 pm DF chromatography column was used.

The GC injection temperature was 250 ° C, splitless mode, and heating was programmed at 40 ° C for 1 min, followed by a ramp of 5 ° C / min at 200 ° C and 10 ° C / min at 260 ° C.

This high temperature was maintained for 5 minutes. Mass spectra were acquired in the 29-350 M / Z range with an Agilent 5977 three-scan s-1 MSD spectrometer.

VOC identification was performed on the basis of the matching peak with the library's spectral database (NIST 08) and kovats indices.

The amount of each monoterpene was expressed as a percentage of total monoterpenes.

Table 3 is shown below, including the results of the GC analysis of the hydrolates of Citrus aurantium var. amara and Monarda fìstulosa, with the values expressed as a percentage.

Table 3

With reference to table 3, it is noted that the hydrosol of Citrus aurantium variant amara has as major components linalool (47.7%), α-terpineol (13.83%) and terpenolene (24.82%) while the The hydrosol of Monarda fistulosa is essentially characterized by carvacrol (49.68%) and thymol (45.26%).

Example 4: DEVELOPMENT OF A PREMEDIC ATA GAUZE PROTOTYPE TO BE USED FOR THE ASSESSMENT OF ANTIMICROBIAL EFFECTIVENESS

The aim was to develop a premedicated gauze model that can be used in in vitro studies aimed at evaluating antimicrobial efficacy.

To achieve this, some sterile gauze was soaked in hydrogel based on gellan gum formulated at 50% with Citrus aurantium variant amara hydrosol.

Specifically, a quantity of powder equal to 2% of the established average final volume of the aforementioned hydrogel was dissolved by heat in a quantity of water equal to 50% of the same final volume.

During the cooling phase, a similar amount of Citrus aurantium variant amara hydrolate was added to the solution of water and gellan powder.

Subsequently, the solution was poured on sterile gauze cut out and placed in a Petri dish with a diameter of 6 cm, waiting for it to become solid.

After developing the pre-medicated gauze prototype for the in vitro study of antimicrobial efficacy, several experiments were carried out.

Specifically, gauze formulated with only 2% v / v gellan or with 50% v / v gellan (2% v / v) hydrolate (Citrus aurantium variant amara or Monarda didyma or Monarda fistolosa) were sown with 10 microliters of a 0.5 McF suspension of each bacterium or fungus indicated in point 1.

After incubating the gauze for 24 hours, the presence of microbial growth on each gauze was evaluated and then it was molded on suitable culture media (Sabouraud for fungi and Mueller Hinton for bacteria).

After a further 24 hours of incubation, the growth of the sown strains was evaluated in order to identify their cytostatic or cytocidal activity.

At the end of the first incubation, all the gauze soaked in gellan only (control) showed a fungal but not bacterial growth, while the gauze soaked with hydrolate gellan did not show any fungal or bacterial growth visible to the naked eye. Continuing the experiment, and after the further 24 hours of incubation, the plates printed with gauze soaked in gellan only showed an important fungal and bacterial growth.

This data indicates that gellan alone has no cytocidal or growth inhibitory effect on the strains under study.

On the contrary, all the plates with gauze soaked in hydrogels formulated with the hydrolates, showed a strong inhibition or the total absence of microbial growth, as inferable from table 4.

Table 4, below, indicates the bacterial and fungal growth detected on culture medium after the application of gellan gels, modified or not, previously sown with the strains (fungal or bacterial) under study.

The symbols shown in the table have the following meaning: CTR +: Positive control; (-) absence of growth; (+) rare colonies; (++) moderate microbial growth; (+++) strong microbial growth; (++++) carpet growth.

Table 4

Example 5: STUDY OF THE CYTOTOXIC ACTION OF GAUZES FORMULATED WITH HYDROGEL AND HYDROLATE.

The study aimed to evaluate the cytotoxic action of gauze formulated with hydrogel of Citrus aurantium variant amara hydrosol or Monarda fistula hydrosol.

The study was conducted on gingival fibroblast cells, which were treated with culture medium previously incubated, for 24 hours, with 2% v / v gellan hydrogel and Citrus aurantium variant amara hydrolate or Monarda fistula hydrosol.

The cytotoxicity of the hydrogels was assessed by the MST test (Promega, Madison, WI, USA test).

The treated culture medium was used as it is (TQ) and diluted to 50% (1: 2), 25% (1: 4) and 12.5% (1: 8) in base medium.

The cells were resuspended in 200 μl of base medium and seeded in 96-well plates and incubated for 24h until a subconfluent monolayer was obtained.

Cell viability was assessed at 24h and 48h after adding the previously conditioned medium.

The MTS test was performed in accordance with the operating protocol established by the manufacturer and each experiment was done in triplicate.

With reference to flg. 1, it is observed that the substances released by the hydrogel in the culture medium after 24h of incubation were toxic for the gingival fibroblasts treated with the medium conditioned by the hydrogel formulated with Monarda fìstulosa hydrosol, while they did not show any cytotoxicity for those treated with l hydrogel formulated with hydrosol of Cìtrus aurantium variant amara.

The data indicates a reasonable certainty in the use of gauze formulated with hydrosol of Cìtrus aurantium variant amara.

Example 6: RELEASE KINETICS OF ACTIVE COMPONENTS PRESENT IN PREMEDICATED GAUZE

The set goal was to evaluate the release kinetics of the active ingredients in 24 hours, the estimated residence time of a dressing.

For the study, 2% v / v gellan hydrogel as control and 2% gellan hydrogel modified with hydrosol of Cìtrus aurantium variant amara or with hydrosol of Monarda fìstulosa at 50% v were prepared in 6 cm diameter plates. / v; 5 mL of physiological solution was deposited on the surface of the hydrogels and incubated for 1h, 3h, 6h, 24h and 30h.

At the end of each incubation, the samples were taken and stored at 4 ° C until the qualitative-quantitative analysis carried out using high performance liquid chromatography (HPLC), infrared (IR).

A THERMOQUEST HPLC system (manufactured by Shimadzu, Kyoto, Japan), equipped with two LCGA pumps and a UV / Vis SPD 10A detector (Shimadzu), was used for the analyzes.

At the end of the column a UV-Vis lamp was connected, set to the absorbance wavelength of the compounds analyzed. The analyzes were performed using the following isocratic conditions: (i) Solvent A: Acetonitrile / H2O / Acetic Acid 95: 34: 1, (ii) Ambient T °, (iii) λAss = 274 nm, (iv) flow rate = 1 ml / min.

The samples, if necessary, were diluted in acetonitrile at different V / V ratios based on their [C] and subsequently filtered on RephiQuik Phobic PTFE 0.45 µm filters.

With reference to Figure 2, it is observed that in the analyzed samples there is an increasing trend of active ingredients of the hydrosol released into the physiological solution as a function of time.

The maximum release peak is observed 3 hours after application, with a progressive decrease of active ingredients up to 30 hours.

From the analysis, thanks to a comparison with some standards, it was possible to identify the presence of carvacrol which is one of the main components of the hydrosol of Monarda fìstulosa.

Therefore, in a time-dependent manner, the active ingredients of the hydrolates responsible for the antimicrobial action described are also released.

The data obtained from the analysis show how the sample "1h" has quite intense peaks, an intensity that becomes even more relevant in the sample "3h" (for both types of sample tested), an indication of the increase in the concentration of this compound in the sample analyzed and therefore an indication of a greater release of the hydrolate components by the gellan hydrogel.

This growing trend of the released material gradually begins to decrease, maintaining a trend that can be considered constant up to 30h. This data confirms, also for the gellan hydrogel modified with hydrolates, what is already known in the literature, namely that the gellan hydrogel releases its aqueous component constantly over time.

Therefore, in a time-dependent manner, the active ingredients of the hydrolates responsible for the antimicrobial action described are also released.

With reference to fig. 3, the trend as a function of the time of the release of carvacrol is shown (the two characteristic peaks at 5.7 minutes and 6.3 minutes have been taken) main component of the hydrosol of Monarda fìstulosa identified in the sample obtained from the hydrogel of gellan made with the same hydrosol.

As shown in fig. 3, the greatest release of the active ingredients occurs in the first 3 hours of contact and then gradually decreases up to 30 hours. The figure shows how the intensity of the two peaks corresponding to the carvacrol is greater after the first and third hours while it tends to decrease in the following hours. This data confirms the controlled release over time of the active ingredient "carvacrol" when integrated, in the form of hydrosol, into the gellan hydrogel (Gelid made with M. fistulosa hydrosol indicated with the abbreviation Gelid MF in fig. 3).

Claims (13)

CLAIMS 1. Medical device including: - a support for skin application; - a medicament associated with said support and intended to be placed in contact with an injured area of the skin; characterized in that said medicament comprises a hydrogel having the following composition: - gellan gum gel; - calcium acetate; - hydrophilic hydrosol of Citrus aurantium flowers; - preservatives for topical human use. 2. Medical device as in claim 1, characterized in that said gellan gum gel is between 1% and 3% by volume with respect to a total volume of the hydrogel. 3. Medical device as in claim 1 or 2, characterized in that said calcium acetate is between 0.03% and 0.05% by volume with respect to a total volume of the hydrogel. 4. Medical device as in any one of claims 1 to 3, characterized in that said hydrophilic hydrolate of Citrus aurantium flowers is between 45% and 55% by volume with respect to a total volume of the hydrogel. 5. Medical device as in any of the preceding claims, characterized in that said preservatives for topical human use are between 0.15% and 0.35% by volume with respect to a total volume of the hydrogel. 6. Medical device as in any one of the preceding claims, characterized in that said hydrogel comprises a hydrogel in the solid state. 7. Medical device as in any one of the preceding claims, characterized in that said support is a fabric gauze. 8. Medical device as in any one of the preceding claims, characterized in that said hydrophilic hydrolate of Citrus aurantium flowers comprises hydrophilic hydrolat of Citrus aurantium flowers in the amara variant. 9. Method for the production of a medicament that can be associated with a support for skin application, suitable for defining a medical device when mutually associated, in which the method includes the steps of: - creating a volume of hydrogel by dissolving a second quantity of rubber powder of gellan in a first quantity of water, by heating to a temperature higher than 40 ° C; the method being characterized in that it comprises adding to said volume of hydrogel a third quantity of hydrophilic hydrosol of Citrus aurantium flowers, and in that said adding comprises adding in a cooling step. 10. Method as in claim 9, characterized in that said first and second quantities form a solution having a volume equal to 50% of the final volume of said hydrogel. 1 1. Method as in claim 9 or 10, characterized in that said third quantity is 50% of the final volume of said hydrogel. 12. Method as in any one of claims 9 to 11, characterized in that said cooling occurs at a temperature lower than 40 ° C. 13. Use of hydrophilic hydrosol of Citrus aurantium in a medical facility for the treatment of skin diseases, in particular lacerations or wounds or burns.