IT201600116727A1 - COMPOSED FOR THE HEALING OF WOUNDS - Google Patents

Description

DESCRIPTION

Field of application

The invention relates to a compound for the treatment of skin lesions and, in particular, for the topical treatment of difficult wounds, consisting of amino acids, hyalaronic acid and other compounds useful for tissue healing, including some vitamins.

State of the art

It is known that the skin is the largest organ in the human body, it represents a mechanical and immunological barrier, as well as having a role in thermoregulation and in tactile, thermal and pain sensitivity.

The skin is made up of two layers: the thin epidermis and the thicker dermis, under which the subcutaneous adipose tissue is located.

The epidermis is in turn composed of four layers: stratum corneum, granular, spiny and basal, and mainly contains oheratinocytes, melanocytes, Langerhans cells and Merkel cells.

The epidermis is associated with the functions of protection from trauma, microbiological contamination and loss of liquids, it is also a screen for ultraviolet rays thanks to the synthesis and deposition of skin pigments.

The dermis divides into the superficial papillary dermis and into the. reticular dermis, placed in depth.

The dermis mainly contains fibroblasts, mast cells, histiocytes, monocytes, lymphocytes and Langerhans cells and its integrity is ensured by a support matrix consisting of fundamental substance and two types of fibrous proteins: collagen, which is the main component of the dermis and ensures resistance to stretching forces, and elastin, which represents the minority fraction and is responsible for skin elasticity.

The skin appendages, such as hair follicles, sebaceous, apocrine and eccrine glands are also located in the context of the dermis.

The functions of the dermis are linked to the rich vascularization that allows the metabolic exchange between blood and interstitium, the immune response, the repair of lesions and the regulation of epidermal cell replication.

The hypodermis, composed mainly of adipose tissue, represents the main energy reserve and participates in the regulation of body temperature.

The hypodermis also has a plastic function and acts as a protection against trauma.

Wound healing is defined as the organism's response to the loss of physical integrity of a tissue or organ, aimed at restoring homeostasis and stabilizing the physiology of the whole organism.

The healing process must be understood as a systemic response, with an impact on the organism that goes far beyond the continuous solution itself, and represents one of the most complex physiological processes that occur during adult life.

Homeostasis is re-established essentially goes through two processes:

1) Cicatrization, i.e. the replacement of the injured or lost tissue with a different cellular-fibrous matrix that promptly restores the physical and physiological continuity of the affected organ

2) Regeneration, i.e. the restoration of the original architecture of the tissue through the reactivation of its development processes, so that the regenerated tissue has the same functional capabilities as the damaged one.

Scarring and regeneration are in a unique dynamic equilibrium for the different tissues and organs and in most cases the final repair is a combination of both processes whose relative contribution depends on the regenerative capacity of the tissue and the depth of the lesion.

For example, superficial skin wounds heal by epithelial regeneration while deep wounds, in which the structure of the extracellular matrix is damaged, heal by scarring.

With reference to the temporal duration of the healing processes, acute is defined as the wound generated by an injurious event that occurred in the last 3 or 4 weeks.

If the wound persists beyond 4 or 6 weeks it is defined as chronic, a term that includes injuries that can last for months or years.

To determine whether a wound heals in physiological times or takes on the characteristics of chronicity are factors that alter the normal healing process, perpetuating the inflammatory phase and hindering the transition to the proliferative phase or its completion.

In fact, if an acute wound is characterized by a lively response of cell proliferation and migration, low levels of inflammatory and protected cytokines and a normal cellular response to growth factors, in chronic lesions a reduced rate of mitosis and migration is observed, the persistence of 'inflammatory infiltrate that produces abundant levels of cytokines and protessi, a consequent senescence of the cells that become unresponsive or refractory to growth factors,

The wound microenvironment plays a crucial role in the healing process.

The microenvironment of a wound is defined as the extracellular compartment in which the cells that play a role in tissue repair are immersed and in which the factors that regulate its activity are released.

The microenvironment consists of an internal component, i.e. the compartment just below the wound surface, and an external component, i.e. the external compartment immediately adjacent to the surface, in continuous exchange with each other.

Wound healing processes are extremely complex and only partially understood, however the first-rate role played by the microenvironment is now evident, which must be understood as an active and dynamic component of the wound, seat of the direct regulation function of cellular activity. .

It is precisely from the reciprocal interaction between cells and their microenvironment that the maintenance of skin homeostasis results.

Understanding the functional complexity of the wound microenvironment has allowed not only to better delineate how various factors such as advanced age, ischemia or bacterial infections can alter and prevent the normal healing process, but has also paved the way for the possibility of therapeutic action on defects. of tissue repair through the manipulation of the microenvironment.

This concept guides the modern activity of developing tissue engineering strategies to modulate and recreate the precise biophysical environment in which biological healing processes can best develop.

The humid microenvironment.

The skin has a low water permeability and acts as a barrier to the evaporation of fluids.

The amount of fluids lost through the skin is referred to as "water vapor transmission rate (WVRT)" and following a damage that interrupts the continuity of the skin barrier it undergoes a dramatic increase, with a tendency to dryness of the wound.

The transition from traditional dressings that operated the absorption of liquids up to drying to advanced dressings that reduce evaporation and increase the humidity of the microenvironment has led to a marked improvement in the management of difficult lesions.

Evaporation is in fact a phenomenon that consumes energy, thus subtracting the calories necessary to support the repair processes, and also causes a decrease in the temperature of the wound, another factor capable of significantly influencing tissue healing.

This is explained by the fact that the temperature in acute wounds increases due to local vasodilation, thus allowing the body to transport more oxygen and nutrients to the damaged area.

It has been widely demonstrated that a moist / wet microenvironment increases wound healing speed compared to a dry microenvironment and also improves the quality of repair.

In fact, scarring and contraction are reduced, the speed of migration of epithelial cells increases and therefore closure by surface re-epithelialization, the survival of skin grafts is increased.

The pH of the wound.

Intact skin is naturally acidic with a physiological pH between 4, 8 and 6, mainly determined by the secretion by keratinocytes of equivalent organic acids which constitute the so-called skin acid mantle, a protective film from the external environment.

The acidic surface of the skin protects the organism from bacteria and fungi that require a pH> 6 to replicate.

When a continuous solution of the skin barrier is realized, the pH on the wound surface tends to increase as a result of the diffusion of interstitial fluids at a more alkaline pH and the extravasation of plasma from the damaged capillaries.

On the other hand, acute inflammation stimulates the formation of an acidic environment in the context of the lesion: the final result is that the wound bed can become more acidic or alkaline based on the pathophysiology of the damage and this influences the effectiveness of the precesses. healing carried out by the body.

It has been shown that in wounds that heal in a short time the pE of the wound surface becomes lower.

The acidic microenvironment is believed to play a role in decreasing the risk of infections and may facilitate the formation of granulation tissue.

"In vitro" studies have also shown that an acid environment is able to promote neoangiogenesis and enhance the proliferation and migration of keratinocytes and fibroblasts.

Conversely, an alkaline microenvironment hinders healing by promoting bacterial infection and biofilm formation; moreover, the proteases secreted by both the bacteria and the host inflammatory cells have a dramatically higher activity at alkaline pH, favoring proteolysis rather than the synthesis of matrix necessary for the closure of the lesion.

In fact, proteases have their maximum catalytic activity in a pH range between 7 and 8 and decreases when the pH is lowered: when the pH = 4 they are irreversibly inactivated.

Therefore, it is important that the lesion is maintained at a pH below 4, while remembering that these enzymes are necessary for healing.

The pH of the microenvironment also affects the release of oxygen from the blood compartment to damaged tissues,

A decrease in pH of 0.6 units correlates with a 50% increase in oxygen release and with an increase in acidity of 0.9 the release of oxygen also increases fivefold.

This characteristic takes on particular relevance in chronic wounds, for which hypoxia represents one of the main factors preventing healing.

In fact, in these lesions, the probability of healing is high if the oxygen tension (pC2) in the microenvironment is greater than 40 mrnHg, while it is lower for levels below 20 mmHg.

However, atrophy and fibrosis of the microcirculation are a permanent obstacle to the diffusion of oxygen and this further aggravates hypoxa by triggering a vicious circle that prevents tissue repair.

Therefore, any factor capable of influencing even a small part of the pH of the wound can have significant consequences on tissue oxygenation.

From these considerations on the role of the acidic microenvironment of the wound, it emerges that pH can represent a significant factor in predicting treatment outcomes and in the development of new therapies for chronic wounds.

In addition to the above, since the stability and binding of biomolecules occurs within narrow pH ranges, all therapies focused on the delivery of antibiotics, growth factors, protease inhibitors to the wound bed must take into account the modulation of the pH. of the microenvironment.

Currently the pH is not monitored in clinical practice since, despite the great development of new devices, for this purpose, a method that fully satisfies the criteria of accuracy, simplicity and efficacy has not yet been found.

In the future, however, the pH of the microenvironment could become a measure of the outcome validated as the size of the wound is at the moment, capable of determining the effectiveness of a treatment, guiding the clinician in therapeutic choices and finally directing the search for new strategies for approach to wounds.

MMPs.

The extracellular matrix of wounds plays a key role in regulating cell adhesion, migration, proliferation and differentiation during tissue repair.

The quantity and organization of a wound matrix are determined by a dynamic balance between the processes of synthesis, deposition and degradation.

Loss of this equilibrium can cause abnormal matrix accumulation (due to excessive synthesis, inadequate degradation or both) or abnormal degradation (due to inadequate synthesis, excessive degradation or both).

Fibroblasts and, to a lesser extent, keratinocytes are mainly responsible for the synthesis and deposition of the wound matrix, composed of numerous types of collagen fibers, glycoproteins, elastin, glycosaminoglycans and proteoglycans.

Numerous cell types, on the other hand, are able to express both numerous families of proteases and their inhibitors.

In addition to being sacred by the cells involved in the repair process such as fibroblasts and endothelial cells, the protected cells are in fact also produced by immune cells stimulated by the inflammatory process.

Bacteria are an additional source of protection in wounds, both because they stimulate the immune system and because some can themselves secrete protected.

Protected or proteinases are enzymes capable of degrading proteins into peptides and amino acids.

In this broad enzyme category the most important in the wound healing process are matrix metalloproteases (MMPs).

MMPs are a family of over 20 enzymes characterized by the presence of a zinc-protease site, distinct from other connective-degrading proteases such as neutrophil elastase, ctepsin G, kinins, plasmins and others that are serine-proteases and not me thallus protease.

These enzymes have the ability to break down collagen and other connective proteins.

MMPs are distinguished from each other by substrate specificity and include interstitial collagenases (MMP-1, -2 and -3) which degrade fibrillar collagen types I, II and III; gelatinases (MMP-2 and -9) which degrade amorphous collagen and fibronectin; stromalisins (MMP-3, -10 and -11) which degrade various components of the matrix such as proteoglycans, laminin, fibronectin and amorphous collagens; membrane-bound matrix metalloproteases (MBMM).

This class of enzymes plays a fundamental role in all phases of wound healing: in the inflammatory phase they participate in the elimination of the damaged extracellular matrix (autolytic debridement) and in the proliferative phase they have the role of degrading the capillary membrane to favor angiogenesis and contribute to the loss of junctions between cells and their migration; they also mediate the modification of the composition of the extracellular matrix necessary for the granulation tissue to be replaced by a scar.

During a normal tissue repair process, protease levels undergo a rapid initial increase with a peak around the third day and then begin to decrease around the fifth; this trend correlates with the characteristics of the inflammatory infiltrate, being the proinflammatory cytokines the most powerful stimulus to the secretion of these enzymes.

If the balance between the levels of proteases, and in particular MMPs, and their inhibitors is altered, enhancing the degradation of the matrix with respect to its synthesis and deposition, the healing process is compromised.

Factors acting by modifying the microenvironment, such as pH or bacterial infections, can contribute to altering this delicate balance, but there are wounds that do not heal even when the assistance provided to the patient is optimal and the absence of infections is ascertained.

In these cases, persistent inflammation with high protease activity is believed to be the primary cause of the failure to progress through the healing stages.

Several studies on animals and humans have in fact shown that the activity of proteases and in particular of MMFs and human neutrophil elastase is higher in wounds that do not tend to heal.

Although the reasons for the imbalance between the increased activation of proteases and their reduced inhibition have not yet been precisely delineated, the elevated protease activity is the most reliable biochemical marker currently available for predicting difficult healing of both acute and chronic wounds.

Various interventions are already available to reduce protease activity in wounds where it is suspected to be excessive and are based on three basic principles:

II treatment of the triggering cause and the removal of other factors capable of aggravating the state of the wound such as ischemia, malnutrition or pressure;

Optimizing the wound bed and the state of the patient, which means eliminating proiufianimating stimuli through regular cleaning of surface debris, debridement of necrotic tissues, the use of antiseptic dressings to control the bacterial load and anti-inflammatories for control direct inflammation, dressings or devices to remove protease-rich exudate are also important;

The modulation of the protease activity through specific dressings.

The majority of these interventions are awaiting studies confirming their effectiveness.

Further research will be able to better define the role of monitoring of protease activity in clinical practice and make it a valuable tool in the choice of therapeutic management.

RCS.

Free radicals are atoms or molecules that have a single unpaired electron on the outer orbital.

This configuration is highly unstable and the energy is released through reactions with adjacent molecules, both inorganic and organic, which are damaged.

Furthermore, free radicals trigger autocatalytic reactions by means of the molecules with which they interact which in turn are transformed into free radicals, expanding the phenomenon.

Reactive oxygen species (ROS) are a type of free radicals derived from oxygen.

In the human body, ROS are a normal product of mitochondrial breathing processes and energy production, but cells have defense systems to prevent them from causing cell damage.

Another important source of ROS are leukocytes, in particular neutrophils and macrophages, for which reactive oxygen and nitrogen species represent the main mechanism of destruction of bacteria, necrotic tissue and other unwanted substances.

Oxygen free radicals can be released into the extracellular environment by leukocytes recruited in an inflammatory site following exposure to microbes, cytokines and immunocoraplexes or following a stimulus of phagocytosis.

In physiological conditions, there are antioxidant systems that inactivate radical species in order to prevent them from causing cell damage.

If ROS production increases beyond the antioxidant power of cells or the extracellular environment, an excess of free radicals is generated, a condition called "oxidative stress".

This phenomenon is involved in numerous pathological conditions such as cancer, degenerative diseases, accelerated aging.

The free radicals can in fact attack:

organic molecules which are fundamental constituents of cells such as lipids, with consequent alteration of the fluidity and functionality of the membranes;

proteins, whose structural alteration affects enzymatic functions;

DNA, in which they are able to generate mutations; intracellular signaling molecules, with induction of programmed cell death.

Oxidative stress is also involved in wound healing defects, in fact the acute inflammation generated by tissue damage and the continuous presence of bacteria in the solution represent a powerful stimulus to the production of free radicals by leukocytes.

If the production of ROS is excessive and the microenvironment of the wound takes on a strong oxidizing power, the damage mediated by these can cause a chronic inflammation, stopping the reparative activity and favoring tissue degeneration.

Simxintente a glove reported for MMPs, with which KOS are in a relationship of mutual stimulation, the correct management of inflammation of the microenvironment and bacterial infections could significantly reduce oxidative stress and increase the chances of healing,

Microbial load and wound infection.

The human body is a dynamic ecosystem physiologically inhabited by a great variety of microorganisms which collectively are called microbiota.

Normal adult skin is inhabited by trillions of bacteria, fungi, viruses and parasites, whose replication is in balance with the host's immune defenses so that they do not normally cause infections but rather play a fundamental role in maintaining health. .

These microorganisms are defined as "commensal" as opposed to "pathogenic" microorganisms, which are not part of the normal microbiota and which, when they come into contact with a host, can cause infection if the immune system fails to neutralize them and delete them.

We want to highlight how the mere contact of a microorganism with a host is not necessarily followed by a microbial replication such as to cause an infection, which in order to develop requires the simultaneous presence of several factors, both with regard to the host and the invader. .

The microbial load, that is the number of microbes present in a certain tissue unit considered, and the virulence, that is the ability that the different microorganisms have to replicate and invade the host with the same microbial load, are factors of the pathogen.

On the other hand, the host presents a series of defenses which together constitute the host's resistance.

An adequate bacterial load and the presence of specific virulence factors are necessary, but not sufficient, for a microorganism to invade, proliferate and create damage: in fact, the microorganism-host relationship is a dynamic relationship and for an infection to develop it must be unbalanced the balance between these factors and the defensive capabilities of the body's immune system.

From the previous considerations it is understood that all wounds, representing an interruption of the integrity of the skin barrier, are contaminated, but only an excessive number of bacteria is able to interfere with the healing process.

Typically, a quantitative culture of 10 bacteria per gram of tissue is considered diagnostic of infection; however this value is not universally applicable because the more virulent bacteria can infect with a much lower charge.

Additionally, the presence of diabetes, ischemia, or other host comorbidities can further lower the threshold needed to establish true infection.

The situation is made even more complex by the evidence emerging from modern research on bacterial biofilms. so in reality only a small fraction of those 10 bacteria would be sufficient, under some conditions, to generate a biofilm and hinder the healing process.

Therefore, since the number of bacteria individually considered to be little indicative of the impact of these on the ferine and on the healing process, we prefer to use a terminology that also takes into account the bacterial virulence and the response of the host:

A wound is defined as contaminated by the presence of bacteria, without active proliferation;

□ It is defined colonized if the bacteria are multiplying but without this having induced an immune response in the host (host reaction);

Z Critically colonized is the expression that identifies the moment in which the host's response is no longer sufficient to control bacterial multiplication;

Finally, infected is the wound in which there is a continuous expansion of the number of microorganisms despite the associated host response. Bacteria are capable of altering the wound healing process in various ways.

Significant contamination alters lactic acid production, pH and the expression of proinflammatory cytokines and MMPs, trapping the wound in a self-sustaining state of infamination.

The inflammatory state generated alters the microenvironment of the wound enriching it with free radicals, toxins and proteases, consequently the growth factors are degraded, the assembly of the components of the matrix is prevented and proteinaceous debris is generated which form a pasudoescara.

Clinically, the first sign of a critically colonized or infected wound is the gradual slowdown until healing of a previously healing wound stops.

This manifestation is particularly important as it allows an early diagnosis and immediate intervention: ■ in fact, a wound whose healing rate slows down should in fact be considered infected until proven otherwise.

Other signs of increased bacterial proliferation and / or overt infection are an increase in pain in the periwound area, worsening of edema, increased exudation and possible appearance of purulent discharge, appearance of an intense and unusual bad odor, up to the cellulitis with fully manifest inflammation.

To restore homeostasis altered by bacterial presence and promote healing, there are essentially three therapeutic strategies:

I Control of the bacterial load, that is to limit the quantity of microorganisms that come into contact with the wound and prevent their excessive replication. This is most commonly accomplished through regular wound cleaning, saline flushing, non-viral tissue debridement, edema reduction, and the use of appropriate dressings.

LI Use of antiseptics, ie substances capable of killing microorganisms or stopping their development; these molecules have a very variable mechanism of action being able to act through the blocking of vital enzymatic reactions, inhibition of protein synthesis, alteration of intracellular structural components or of membrane permeability; however, they have the common characteristic of being poisons of the protoplasm of all cells, thus resulting toxic for all types of living cells, including those of the host and for this reason they are reserved for external use antiseptics commonly used in clinical practice as they have good efficacy on bacteria without significantly damaging human cells are sodium hypochlorite, iodiopovidone, silver, chlorexxdin, propyl betaine.

Pharmacological therapy using antibiotics, with local or systemic action.

Antibiotics are a large group of molecules with different structures and myriads of mechanisms of action which are characterized by the fact that their receptors are microbial components not common to humans; unlike antiseptics, they are therefore poisons of microbial cells, but not of human ones, even if humans can still be damaged by side effects.

Wound marjoram is effectively managed through the microbial load control mechanisms listed above, capable of reducing contamination and progression to colonization.

The control mechanisms are also effective in controlling bacterial proliferation in wounds already colonized but not critically.

Critically contaminated and infected wounds also require the application of antiseptic solutions and in the case of frankly infected wounds, topical antibiotic therapy is usually required.

In the majority of cases, systemic antibiotics are not necessary and should be reserved for selected cases, also in consideration of the fact that their action is closely linked to their transport to the tissues that must be adequately perfused, so that they would not be very effective in the majority of cases. chronic lesions in which vascularity is often compromised.

However, there are conflicts in which systemic antibiotic therapy is of great importance, particularly in all wounds complicated by surrounding cellulite; they are also administered in wounds contaminated by oral flora or caused by animal bites and in those with mechanical implants.

Presentation of the invention

An object of the invention is to improve the known art.

Another object of the invention is to develop a compound for the healing of wounds which is effective, rapid, even in the presence of ulcerative pathologies, and substantially free from side effects.

According to an aspect of the invention, a wound healing compound is provided, in accordance with the characteristics of claim 1.

Further aspects of the invention are indicated in the dependent claims.

The invention allows to heal wounds of organic tissues in a complete and rapid way and without the onset of infections and side effects, even in the presence of ulcerative pathology.

Brief description of the drawings

Further features and advantages of the invention will become more apparent from the detailed description of a preferred, but not exclusive, embodiment of a wound healing compound, illustrated by way of non-limiting example in the following description.

The compound according to the invention consists of a formulation for topical use which includes amino acids, hyaluronic acid and vitamins including vitamins C and E.

This compound promotes wound healing in patients suffering from traumatic, diabetic or vascular ulcers.

The compound is preferably in the form of an aqueous gel, containing thickening polymers including acrylic polymers, cellulose derivatives or xanfchan gum, and includes other commonly used excipients, such as some preservatives.

The amino acids included in the formulation include collagen precursors:

- L-glycine

- L-lysine

- L-proline

- L-valine

- L-leucine

- L isoleucine

L-serine.

The amino acids include the sulfurates SH-cysteine and SH-methionine, which have the ability to inhibit the activity of metalloproteases and act by prolonging the duration of action of hyaluronic acid. Other amino acids included in the formulation are: - L-histidine

- L-phenylalanine

- L-tyrosine

- L-threonine

- L-tryptophan

This amino acid pool provides locally applied tissue repair precursors, compensating for their inability to reach the affected site systemically, as difficult wounds are ischemic and severely damaged.

The amino acid concentration varies between 0.01 and 10% of the weight of the entire compound.

Hyaluronic acid or its derivatives improve the lesional environment through various mechanisms.

The extreme length of the molecule, together with its degree of hydration, allows more hyaluronic acid polymers to organize themselves to form a reticular structure that has mainly 2 functions: to create a molecular substrate that maintains the shape and tone of the tissue; act as a filter against the free diffusion of bacteria and other infectious agents inside the fabric.

Hyaluronic acid or one of its salt is present within the compound in a range between 0.01 and 5% of the weight of the entire compound.

Ascorbic acid (vitamin C) or its derivative are able to assist and promote the tissue healing process, as they act as cofactors in the skin synthesis of collagen.

It is also able to lower the pH of the micro-environment and has antioxidant functions.

Ascorbic acid or a salt thereof are present within the composition in a range between 0.01 and 2% of the weight of the entire compound.

Tocopherol (Vitamin E) is a powerful fat-soluble antioxidant.

Alpha-tocopherol is the most potent and biologically active form.

Vitamin E plays its antioxidant role against free radicals, acting as a stabilizer of biological membranes.

Its anti-oxidant action, together with the pro-lipidizing activity, make Vitamin E an ideal candidate for healing difficult ferrites.

In particular, it carries out a defensive action against an excessive production of oxygen free radicals, also in this case improving the lesional microenvironment.

Tocopherol is present in a percentage between 0.01 and 2% of the weight of the entire compound.

Detailed description of a preferred embodiment.

The following examples illustrate some embodiments of the compound according to the invention.

EXAMPLE 1:

COMPONENT% w / v

Γ.-1 leucine 0.60

L-valine 0.60

i - isoleucine 0.60

L- histidine 0.60

L- glycna 0.20

L-proline 0 ^ 20

f lysine 0.60 Menomila SII 0.30 Cisterna SH 0.40 L- phenialanma 0.40 L- ur hexine 0.30 T - (take between 0.40 L- tri padane 0.20 I j- scrin 0.20 Hyaluronic acid sodium salt 0.10 Ascorbic acid 0, 10 Vitamin E acetate 0.05 (Sum of xanlban

Water Up to 100 a

EXAMPLE 2:

C0M7 <J> 01NIìNTF. % W / V L-i cooking 0.60 L-valine 0.60 E- isoleucine 0.60 L- histidine 0.60 Γ - die ina 0.20 T --proline 0.20 L- lysine 0.60 Vletionine SII 0.30 Cisterna SH 0,40 1, - iemìalanine 0,40 Ϊ - tyrosine 0JQ L- trccnine 0,40 L- tri pio inno 0,20 L- se fine 0.20 Uranic acid sodium salt 0, 10 Ascorbic acid 0.10 Vitamin K ace Side 0.05 Tixoxry]

Up to water

100g

EXAMPLE 3:

COMPONENT W / V L- glyein 0,20 L-proline 0.20 T - lysine 0.60 Metions n a SII 0.30 <'> Cyst ina SH 0.40 L- phenylulanine 0.40 L- 1 irosis 0.30 L- threonine 0, 40 L-Lrip solane 0.20 i.- senna 0,20 Acid i al uremic sodium salt 0.10 Ascorbic acid 0,10 Vitamin F acetate 0.05 Apple trees ì id red cti I ce 11 dose (MH FC)

Water Up to i OOg

EXAMPLE 4:

COMPONENT% w / v L-lcncinu 0.60 L-valine 0.60 L- kitchen iso 0.60 Γ histidiiia 0.60 L- gl theine 0.20 L-proIin 0.20 E- lysine 0.60 Mcdonin SII 0J0 Cisterna SH 0.40 L - l <'> enHalanine 0,40 Γ.- shot siires 0,20 L- irennin 0.40 L- profane tri 0,20 L- scrin 0,20 Hyaluronic acid or sodium salt 0.10 Ascorbic acid 0.10 Vitamin E acetate 0.02 fdrossictilcel luiosa (HLC)

Up lo I water 100g

EXAMPLE 5:

COMPONENT% W / V L- le uc ina 0.60 I.-Currency 0.60! .- isoleucine 0.60 L- isti din a 0.60 L- idi dna 0.20 L-proline 0.20 L- lysine 0.60 Cisterna SH 0.40 L- phenylalanine 0.40 L- sine shot 0.30 L- towing 0.40 Profane L-tri 0,20 L-scrin 0.20 uro-nino acid sodium salt 0.10 Ascorbic acid 0,10 Vitamin E acetate 0.05 Xamhan gum

Water Up to 100c

EXAMPLE 6;

COMPONENT% w / v L-Ìcucina m

L-valine ojfiO L- J sol eucine 0.60 isiidine 0.60 L- gl i a 0.20 L-proline 0.20 L- lysine 0.60 Meli ornila SII 0.30

L- iemiaianin 0.40 L- thi rosins 0.30 I.- ireenine 0.40 L- tripy Healthy 0.20 L- serrila 0.20 Ini uremic acid saie sodium 0.10 Ascorbic acid

vitamin E acetate

Goni ma of xanthan

up to

EXAMPLE 7:

COMPONENT

L-l cooking 0.60 L-goat 0.60 L- i sol cooking 0.60 Γ - gliein 0,20 L-proline 0,20 [.- lysine 0,60 Meli Divina SH 0,30 Cysteine SII 0.40 L-scrin 0.20 Acid i al «. ironic sodium salt 0.10 Ascorbic acid 0J 0 Vitamin E acetate 0.05 Xanthan gum

Ac c] uà Up to

EXAMPLE 8:

COMPONENT% W / V L-ìcncina 0.60 L-v aline 0.60 L- isoleucine 0.60 T - histine 0.60 L- filicin 0.20 L-proiin 0.20 L- lysine 0.60 Metioniiia SU 0.30 Cyst ina SU 0N0 L- lenii alanine 0.40 L- tyrosine 0.30 L- threonine 0.40 L - tripy I anus 0.20 L- strin 0.20 Acid or hyaluronic acid 0.10 Acid o ascor hi co 0.10 Xanthan gum .

Water Up io I00g

EXAMPLE 9:

COMPONENT% w / v T. -leu dna 0.60 I go ina 0.60 Γ- i so lotic na 0.60 L- isti din a 0.60 L- idiom 0.20 T, -order 0.20 E- lysine 0, 60 Metioiiine SH 0J0 Ci. SII system 0.40 I.- tenylalanine 0.40 L- lyrosine 0.30 L- threonine 0.40 L- tripiófano 0.20 L- strine 0.20 L-strine sodium 0.10 Vi lamina E steel 0.05 Xanlhan gum

Water LO lOOg

EXAMPLE 10:

COMPONENT% W / V L- gliein 0.20 J -praline <(> Ϊ20 L- lysine 0.60 Mciio'iina SH 0JÓ Cyst ina SH 0.40 L- lenii in foil (Ϊ40 L- liroE-inc 0.30

L- trcoiiina 0.40

L- iryptophane 0.20

T.- scrina 0.20

Addo hyaluronic sodium salt 0.10

Ascorbic acid 0.10

Vitamin F! 0.05

Xanthan gum

Waters Up to

'100g

In practice it has been found that the invention achieves the intended purposes.

The invention as conceived is susceptible of modifications and variations, all of which are within the scope of the inventive concept,

Furthermore, all the details can be replaced with other equivalent elements.

In practical embodiment, the components used, as well as their quantities, may be any according to requirements, without thereby abandoning the scope of the protection of the following claims.

Claims (3)

R IV E N D I CA C IO K I 1. A compound for topical wound healing, characterized in that it comprises a formulation containing amino acids, hyaluronic acid and / or its derivatives, ascorbic acid and / or its derivatives, vitamin E. The compound according to claim 1, wherein the essential amino acids are at least one selected from: - L-lysine - Methionine SH - L-valuna - L-leucine - L-iscleucine - L-histidine - L-phenylalanine - L-threonine - L-tryptophan The compound according to claim 1, wherein the non-essential amino acids are at least one selected from: - L-gii, china - L-prclina - Cysteine SH - L-tyrosine - L-threonine - L-serine 4. The compound according to claim 1, wherein the amino acids are present in a range of between 0.01 and 15% of the weight of the entire compound. The compound according to claim 1, wherein the hyaluronic acid and / or a salt thereof are present in a range between 0.01 and 10% of the weight of the whole compound. The compound according to claim 1, wherein the ascorbic acid and / or a salt thereof are present in a range between 0.01 and 5% of the weight of the entire compound. The compound according to claim 1, wherein the vitamin E and / or a derivative thereof are present in a range between 0.01 and 5% of the weight of the entire compound. 5. The compound according to claim 1, wherein it is in the form of an aqueous gel containing thickening polymers selected from xanthan gum and / or cellulose derivatives and / or acrylic polymers. 9. Use of combinations of amino acids, hyaluronic acid and / or hyaluronic acid salts, for the preparation of a wound healing compound, such as pressure ulcers, diabetic wounds, vascular wounds. The use according to claim 9, wherein said combinations are optionally added to ascorbic acid and vitamin E.