WO2009027823A2 - Pharmaceutical composition for selective stimulation of wound healing processes, dermal-epidermal normal tissular trophism processes, its preparation and application. - Google Patents

Abstract

The present invention discloses pharmaceutical compositions for selective stimulation of wound healing processes, dermal-epidermal normal tissular trophism processes for internal and external use, containing gentamicin sulphate, metronidazole, papain, metronidazole Balsam of Peru, and an excipient or vehicle pharmaceutically acceptable.

Description

PHARMACEUTICAL COMPOSITION FOR SELECTIVE STIMULATION OF WOUND HEALING PROCESSES, DERMAL-EPIDERMAL NORMAL TISSULAR TROPHISM PROCESSES, ITS PREPARATION AND APPLICATION.

Technical Field

The following text aims to describe the most representative pathologies on which this composition has been used.

For a better understanding, it is necessary to start with a brief classification of different wounds, and healing processes and stages.

Introduction: Classification of wounds, healing processes and stages

A wound is an anatomic or cellular discontinuation caused by any injury: Mechanical (wounds, traumas, constant pressure, excessive use, pair organ absence, etc), biological (inflammation caused by bacteria, viruses, fungi, parasite), physical (burns, ionizing and non-ionizing radiation), chemical (drugs, chemical products, vitamin deficit, hormonal imbalance), vascular disorders (atheromatosis, venous and arterial disorders, diabetic vasculopathy, etc) and surgical (injury dehiscence, surgical drainage due to infections, etc).

Healing by first intention constitutes the simple restoration of the continuity of the deteriorated tissues, where there has not been a significant tissue loss or an intense trauma. The potential inflammation or infection is minimal; therefore, a prompt joint of the "lips" of the wound is easy.

Open wounds (with extended traumatized areas or tissue loss, edematized or with severe necrosis) and ulcers (substance loss, characterized by null or slight tendency towards cicatrisation) heal by second intention. This dynamic repair process has been historically, and rather arbitrarily, divided into three different stages:

1. Inflammatory stage: this stage, which usually lasts four to six days, is characterized by formation of blood clots and also by platelet degranulation. Within platelet alpha-granules, there are several Growth Factors (GF), such as: PDFG (Platelet-Derived GF), IGF-I (Insulin-like GF), EGF (Epidermal GF) and TGF beta (Transforming GF beta), all of which are potent chemotactic factors for inflammatory cellular recruitment (First Cellular Recruitment). This way, neutrophil, macrophages and lymphocytes enter the wound, while synthesizing and secreting additional GFs, such as FGF (Fibroblast GF), TGF alpha and IL1 and 2 (Interleukin 1 and 2). During this first stage the provisional matrix (PM) is thus created, basically formed by two proteins: fibrin and fibronectin. This matrix represents a true GF reservoir, enabling controlled GF availability. This GF increased environment leads to what may be called the Second Cellular Recruitment, including mesenchymal cells which originate the next stage.

2. Restore or Proliferative Stage: as keratinocytes, fibroblasts and endothelial cells migrate and proliferate in the wound, under GF stimulation, the number of cells in the wound increases, which means a greater GF production and release by the newly activated cells, with subsequent granulation process and extra-cellular matrix (ECM) formation. This stage superimposes over the previous one, since it starts 48 to 72 hours post injury, it extends over a 2 to 6 week-periods and introduces the last stage.

3. Remodelation Stage: it may extend up to three years. Remodelation implies extra-cellular matrix (ECM) turnover, i.e. the balance between synthesis and degradation processes of its components, which will result in scar formation. During this stage, TGF beta acquires great significance due to its actions at fibroblast metabolism and ECM degrading enzymes or collagenase levels.

There are some variables to consider for a better interpretation and application of study models, e.g. the difference between chronic wounds (such as venous ulcers, diabetic ulcers or decubitus ulcers) and acute wounds. An acute wound fluid or exudation is different from the biochemical and molecular points of view when compared to a chronic wound. It has been stated that a chronic wound fluid lacks some GF or has GF inhibitors, while an acute wound fluid has a large number of GF which stimulates many cell activities.

This subject has been of overriding importance for wound research; i.e., to find therapeutic agents that may "snap out" the lethargy of chronic wounds in order to get them back to the right cicatricial process. Any changes in local physiological variables which produce ischemia, anemia, immunologic disorders, ecstasy or increase of hydrostatic pressure of the affected area, contribute to delay or stop wound cicatrisation.

Devitalized or necrotic wound tissue may facilitate bacterial proliferation. The specific case of a great tissue portion (burns) enables bacterial development and advance. The presence of sphacelus delays the process of cicatrisation. Any factors delaying the healing process make a wound prone to infection. For all practical purposes, a chronic wound will always be considered as contaminated.

Any local application of a drug on the wound should smooth the progress of, at least, one of the aforementioned delicate processes.

Background of the invention

Cicatrizing products:

We will refer to some of the most commonly used products to treat the aforementioned injuries you can find in the market and we used during our clinical experience:

1. Natural products: sugar, honey, Asiatic Pennywort (centella asiatica), aloe, Balsam of Peru, etc.

2. Creams and antibiotic solutions, separately or combined. 3. Membranes, dressings, biofilms.

4. Tissue graft, growth factors, etc.

5. Antiseptic solutions (hydrogen peroxide, chlorhexidine, povidone- iodine, nitrofurazane).

1 - Sugar: it is the cheapest and easiest product to get, maybe the most useful for injuries with cavities and large injuries (sores, ulcers, surgical injuries, etc.). It has good tolerance (adverse reactions are not frequent), but it has one disadvantage, it is not applicable on all kinds of wounds, since it has no antiparasitic, antiviral or antimycotic effects, and the prescribed dose is every four to six hours (a very short interval).

Asiatic Pennywort, Aloe, etc.: although these may be useful for localized injuries and have fibroblastic activity (like the Asiatic Pennywort), they have not been used in medical institutions. Balsam of Peru: local and vulnerary irritant substance. It was often used in compresses to promote epithelial cells growth for the treatment of ulcers, wounds and certain skin diseases, such as scabies.

2. Creams and antibiotic compositions: silver sulfadiazine is, beyond any doubt, the one most generally used, whether in public institutions or in private environments. Even though it is basically promoted as an antibiotic for burns, its practical usage extends to all injuries. Nevertheless, we have proved that it is not always completely effective.

Adverse and allergic reactions have been reported. Products combining antibiotics with fibrinolytics, particularly lotions, act very well on some specific injuries. Although such products may be used to "clean" some wounds, their angiogenic and granulant properties are sometimes poor, especially on degenerative injuries, such as diabetic injuries. These products can be very expensive. Creams or solutions with single antibiotics are restricted to injuries where they act according to their specific indications (e.g. metronidazole in anaerobic infections, Mupirocin against Gram positive bacteria, Gentamicin against Gram positive and negative bacteria, etc.).

3. Membranes, dressings, biofilms: these products need precise prescriptions. Their use by the general public is restricted, and they cannot be used on any kind of injury. They are also expensive.

4. Tissue grafts, growth factors: precise prescription. Some grafts are performed, privately, in Argentina, but this procedure is very expensive. Growth factors: some of them are still in an experimental stage, and some others are used but can only be purchased abroad.

5. Antiseptic solutions:

A - Chlorhexidine: it is the most recommended antiseptic for wound cleansing. In low concentrations, it is useful for flushes and irrigations, and in high concentrations, reduces the bacterial load, but it can also damage healthy tissue. B - Povidone-iodine: antiseptic with milder properties than chlorhexidine, but with a broad spectrum, especially against staphylococci. In some cases, it may delay the process of cicatrisation and cause contact dermatitis. It is worth highlighting that povidone-iodine diminishes its residual activity in the presence of organic material.

C - Hydrogen Peroxide: it is highly effective in concentrations of 3 to 6% to irrigate and clean up dirty wounds due to its effervescence, which is caused by the release of oxygen in the presence of catalase in patient's tissues. Nevertheless, this enzyme decomposes very quickly, highly restricting its in vivo antibacterial action. It has also been proved that in high concentrations it causes inflammation and damages healthy tissues, even granulation tissue.

D - Nitrofurazone: it is the most convenient for local antiseptic usage, Depending on the concentration, it has bacteriostatic or bactericidal activity on most microorganisms, but has no effect on fungi or viruses. Antibacterial activity diminishes a little in the presence of organic material. Nitrofurazone applied locally over skin is mildly irritant and does not interfere with granulation or epithelization of ulcerous injuries. It may cause dermatitis, which can be resolved with drug suppression.

WOUND THERAPEUTICS

We will explain concepts regarding wound treatment in current medicine practice, the description of most commonly used products, its therapeutic action and the differences between them.

Regarding wound treatment, we include it in the current concept of wounds classification and interpretation. Based on this concept, we implemented the healing process of said wounds (medical technique performed by doctors, nurses, etc.) with a chosen product. The technique of classification and stratification of pathologies and protocolization of treatments (products) to be implemented is very frequent in many medical fields. Wound healing is not an exception. Classification protocols and treatment methods of injuries in pathologies, especially degenerative injuries (circulatory ulcers, sores, diabetic foot injuries, etc.) or traumatic injuries (burns, surgical, orthopedic) are the most common. Basically, they convey the same concept: providing higher or lower grades of severity according to extension, depth and quality of compromised tissues. All this might be added to any local complications (infection, necrosis, sphacelus) as well as patient's general complications (renal failure, heart failure, diabetes, immunologic disorders, etc.) As an example: complications are classified in numbers: 1 , 2, 3 or 4, if they affect more tissues (muscles, tendons or if it reaches the bone), which may be infected or not, or with sphacelus remains. From the point of view of evolution, prognosis and therapy of an injury, it is different to treat patients with diabetes, renal insufficiency or heart failure, than patients without any pathologies or basically "healthy".

In our field, although there is a tendency to adopt international therapeutic protocols and to systematize healing procedures, in practice there is still a lot doctors and nurses should learn.

There are some variables to consider in the result of a specific treatment. The product to be used must be carefully selected. Take into account not only the benefits from the pharmacological perspective, but also the benefits for the actual "healing process", and consider what the patient expects from that healing. From the pharmacological perspective, we consider that in grade 2, 3 and 4 severe and complex injuries, the therapeutic action of a wound-healing product is evidenced and tested, since it must be effective starting from tissues that often are not under optimal conditions to generate cicatrisation processes.

It is in severe, complex, chronic wounds and injuries, with severe tissue loss (ulcers, sores, amputations, open surgical wounds, etc.) where the efficiency of the biological process of healing for tissular generation, closure and healing is subject to testing.

The therapeutic action of different wound-healing products will be easier to understand if we approach wound healing as a "biologically dynamic" process. If there is a scar, it is due to a successful result of the delicate processes we mentioned (inflammation, proliferation and remodelation). These processes should develop in a progressive, gradual and organized fashion. Otherwise, there appear complications which will delay healing process.

Any external or internal factor that alters the normal dynamic and evolution of said processes leads to aggravation of injuries and complications. An open injury, which did not generate tissue, is caused because there is no cellular contribution (platelets, polymorphonuclears, fibroblasts, etc.) and the required stimulus (growth factor) to trigger the wound-healing processes. Basically, the wound lacks the specific tissue through which the vessels carry the blood that transports these cells, that is to say, granulation tissue. "Any wound that does not granulate will not bleed; and when something does not bleed, it dies".

As the process continues, a superficial injury (epidermal) aggravates and compromises deeper tissue strata (subcutaneous cell tissue, fascias, and muscles). And it may even reach the bone, and result in further complications. From the practical point of view, we consider it necessary to interpret correctly the biological status of wound evolution and the relevance of a proper healing technique applied by the staff in charge. Given all this evidence, we can assure that simple injuries heal by themselves, and that the therapeutic action of a wound-healing product is tested on complex injuries. We consider that the best product will be the one in which the active ingredients may dynamically activate the healing process in any stage of the injury and prevent or solve possible complications, achieving improvement or complete healing in a considerably short period and with good tolerance.

If this is not achieved, the healing process will stop, injuries will become chronic and complications will arise, as it is frequently observed in daily practice.

Summary of the invention In spite of the existence of the already-mentioned products, and their widespread use, their results were not always satisfactory (particularly in degenerative injuries, sores, ulcers and diabetic foot injuries). There were many infectious complications, delays in the healing process and an increase in amputations' frequency and amplitude, not only in Argentina but also internationally.

We start looking for other alternatives for patients.

We tried a natural and ancient product: the balsam of Peru. In the past it was used non-diluted on injuries, and it had a healing effect on superficial wounds and ulcers, but the gauze would stick to the wound, making it difficult to remove. Besides, allergic reactions to this product were very frequent. It was decided to use a 6% balsam of Peru formula with a base of 50% Lanovaseline. We began to use this solution in simple wounds, observing favorable effects on granulation and epithelization. Nevertheless, there appeared some unsatisfactory results which had to be improved:

1- The materials used to heal some wounds (gauzes and bandages) sometimes showed fluorescent green stains (typical in cases of Pseudomona- aeruginosa contamination).

2- On wounds contaminated with Gram negative and anaerobic bacteria, the granulating response was good, but there were still secretions, and the inflammatory-reactive component lasted longer than on other wounds. 3- Also, this type of wounds usually has a typical unpleasant odor. Applying the solution on them, resulted in a certain deodorant effect; nevertheless, the odor was not completely eliminated.

4- Finally, it was noticed that, even though the presence of sphacelus and tissular detritus diminished the regenerative capacity, they were difficult to remove completely from the wound bed.

Based on these results, it was decided that, on the one hand, it was necessary to broaden the antibiotic spectrum of the formula; and on the other hand, it was also necessary to increase its fibrinolytic capacity. Therefore, the following procedure was followed: A- From an infectologic point of view, we searched for antibiotics which could act mainly against Gram negative and anaerobic germs (since oleoresins have a prevailing antibiotic activity against Gram positive germs). Finally, we decided to add Gentamicin sulphate to the composition, to act against Gram negative germs and Metronidazole to act against anaerobes. Skin infections caused by Gram negatives and anaerobes are not very frequent, but they may appear on diabetic or immunosuppressed individuals.

B- In order to increase fibrinolytic capacity, we chose a natural enzyme, the Papain, commonly used as necrotic tissue debrider. It is extracted from a tropical watermelon, the Carica Papaya (Sliced Pawpaw). It acts on unviable proteins (i.e. necrotic tissue proteins), and it is innocuous to viable tissue proteins (healthy tissue).

C- Balsam of Peru concentration was increased from 6 to 10%. We began to use this new composition on superficial injuries without serious complications, and achieved complete wound healing. However, there was no experience about its use on severe injuries, with compromised healthy tissue, such as muscles, tendons or bones. This new composition was used for the first time on a diabetic patient. His left leg had been amputated below the knee and he had irreversible injuries on his right foot. Given the severity of the case, it was necessary to perform a similar amputation. Faced with the patient and his relatives' refusal to said course of action, it was decided to carry out a mid-foot amputation, hoping to graft the exposed tissue bed, if it achieved the necessary degree of granulation.

Once the surgery was done, the surgical wound was dressed with a product containing antibiotic plus fibrinolytic. After four months of using this product, as there was little cicatricial response, it was decided to try the claimed composition. At first, we started treating the wound every 48 h, and surprisingly, after 15 days, the granulation tissue began to appear, without any injuries in other noble tissues (tendons, bones, and blood vessels), allowing the gradual growth of epithelial tissue, and thus completing the cicatrisation stages.

This innovative phenomenon exceeded all expectations as well as the other wound-healing products effects, since by applying only the composition of the invention "the wound was completely closed with no need for any other therapeutic procedures." This case was led us to use our composition on severe and complex injuries where it had not been applied before. The results were amazing, as it can be seen in the cases listed as examples below.

We may say that the biological evolution of the healing process often deviates from the expected patterns.

According to what we have learned during our experience, we consider that there is often a "biological stop" in the healing process. In these cases, an antibiotic or a dressing alone cannot activate the process by itself. Another activator is needed, one that might be capable of "snapping the wound out of its lethargy". This particular circumstance is translated in practice as the situation faced by patients with chronic injuries, who often change medications, turn to other professionals, and lose their time and money. In many cases, they end up with their injuries getting worse. The "biological activity" of this solution produces an unexpected effect, resulting in a progressive, gradual and selective stimulation of healing stages, and with them, the histological strata needed to form the scar (e.g. where there is a lack of epithelium, only epithelium is generated, and where all strata are missing, all needed strata are generated).

Without necessarily restricting ourselves to any theory, we consider that the main difference between the claimed composition and the rest of the wound- healing products lies in its strong dermal-epidermal tissular generating capacity, even under adverse conditions for healing (such as infection, secretions, devitalized tissues, etc.).

Additionally, the composition offers antibiotic, anti-inflammatory and fibrinolytic capacities, which collaborate with the treatment, avoiding complications that may compromise the healing process. This combination of properties is what strengthens its effects and ensures amazing results in most of the treated cases.

Detailed description of the invention

The pharmaceutical composition for selective stimulation of wound healing processes, dermal-epidermal normal tissular trophism processes for internal and external use, comprises 0.08 to 0.12% by weight of gentamicin sulphate, 0.8 to 1.2% by weight of metronidazole, 0.4 to 0.8% by weight of papain, 6 to 14% by weight of balsam of Peru, the remaining being an excipient or vehicle pharmaceutically acceptable.

The preferred quali-quantitative formulation of the invention is as follows: 1) COMPOSITION 1 Gentamicin sulphate 0.1 g

Metronidazole 1 g

Papain 0.6 g

Balsam of Peru 10 g

Basic Excipient q.s 100 g 2) PREPARATION MODE:

1- Place the basic excipient in a mortar, this composition is made of equal parts of anhydrous lanolin and solid petrolatum, blend it properly until complete homogenization. 2- In another mortar, pulverize metronidazole until reduce it to fine powder and put it into 10 ml of propylene glycol; then add the obtained composition in step 1 in small quantities, blending all together properly.

3- Dissolve Gentamicin Sulphate in 2 ml of boiled and cooled distilled water and then add the previous composition (step 2) and blend it until complete homogenization.

4- Dissolve Papain in 4ml of boiled and cooled distilled water and then add the previous composition (step 3). Blend it.

5- Finally, add the Balsam of Peru very slowly to the previous composition (step 4) and blend it until complete homogenization.

3) CONTROLS

• Resulting pH is 5.8 (measured with a pH meter)

• Homogeneity view

• Extension capability view • Particle size view (undetectable when extended on the hand)

• Resulting color is dark brownish

• While preparing the composition, remember that the metronidazole is photosensitive, so the procedure must be carried out in a dark environment. • Prepared composition is stable in a wide temperature range, which varies between 15 degrees and 35 degrees Celsius. Below this temperature, the composition is so thick that it gets difficult to handle; over 35 degrees it is very oily, and the Balsam of Peru breaks down into hard strands. • Gentamicin Sulphate is an aminoglycoside used to treat infections caused by Gram negative and anaerobic bacteria and several staphylococci strains. Its activity against Pseudomonas generates special interest. • Papain, as a proteolytic enzyme, must be protected from humidity, light and heat. Its maximum proteolytic action is between pH 5 and 8.

4) Bottle in tubes or light-proof plastic pots. 5) It is feasible to use acetylated or ethoxylated lanolin to replace anhydrous lanolin.

Every drug used for this composition complies with quality standards, and were acquired from authorized pharmaceutical wholesalers.

Analysis protocols are attached.

Composition 2: used in odontology

Another embodiment of the composition is equal to composition 1 plus zinc oxide, iodoform or any other material which provides radiopacity to the composition in order to allow the follow-up in treatment evolution, performed through X-rays.

Without limiting to the examples, this composition can be prepared in cream, changing only the basic excipient. As described:

Gentamicin sulphate 0.1 g Metronidazole 1 g

Papain 0.6 g

Balsam of Peru 10 g

Basic Excipient q.s 10O g

Cream

2) PREPARATION MODE:

1- Place the basic excipient in a mortar, which in this composition is a nonionic basic cream.

2- In another mortar, pulverize the metronidazole until reduce it to fine powder and put it into 10 ml of propylene glycol; then add the nonionic basic cream in small quantities, blending properly. 3- Dissolve Gentamicin Sulphate in 2 ml of boiled and cooled distilled water and then add the previous composition (step 2) and blend it until complete homogenization.

4- Dissolve Papain in 4ml of boiled and cooled distilled water and then add the previous composition (step 3). Finally, add the Balsam of Peru very slowly and blend it until complete homogenization.

Composition of nonionic basic cream

OIL PHASE Nonionic self-emulsifiable wax 8.0%

Triple pressed stearic acid 4.0%

Solid petrolatum 5.0%

Liquid petrolatum 9.0%

AQUOSE PHASE

Glycerin 9.0%

Imidazolidinyl urea 0.5%

Universal preservative 2.0%

Polyethylene glycol 1.0% Tween 0.5%

Demineralized water q.s 100%

2) PREPARATION MODE:

1) Heat stearic acid up to 75 degrees Celsius, when it is about to melt, add solid petrolatum, liquid petrolatum and finally, add wax avoiding overheating.

2) Heat water up to 75 degrees Celcius, add the rest of the aquose phase, except the imidazolidinyl urea.

3) Add the composition obtained in step 1 to the other composition obtained in step 2, stirring up to 40 degrees Celcius. 4) When reaching 40 degrees Celcius, add imidazolidinyl urea, regulate pH to 6 and continue stirring up to room temperature. For this formula it was used a well known in the state of the art universal preservative, which composition and preparation is as follows: UNIVERSAL PRESERVATIVE Quali-quantitative Formula Methylparaben 18.0 g%

Propylparaben 2.00 g%

Propylene glycol q.s 100 ml

I Preparation Technique: Place the parabens in a proper container to weight them, then add 86 g of propylene glycol.

By mild heating and stirring, the nipas are completely dissolved. This composition is recommended for general dermatologic use with no severe tissular compromise. This composition is a cream, but it could also be prepared as ovules, embedded gauze, vaginal creams, spray, etc. The composition of the invention is intended to prepare a medicine to be used for:

• The treatment of cutaneous injuries and irritations. Especially to treat acute and chronic wounds, providing a moisturized means to protect the area against friction, abrasion and dehydration, e.g. cutaneous abrasions, areas from where tissue was removed to perform graft procedures; wounds resulting from surgical interventions, decubitus ulcers, varicose ulcers due to venous ecstasy, trophic ulcers, on the course of chronic arterial insufficiency processes, metabolic disorders, 1 and 2 degree burns, necrosis post-radiotherapy, cracks, fistulae, abrasive skin diseases, excoriations of chemical or physical origin.

• Due to its strong stimulating action over granulation and over the wound- healing processes, it is particularly useful on chronic injuries, with great loss of exudative and fibrinous substances, and particularly on diabetic foot injuries (ulcers, exposed tissue bed caused by amputations, sequels to amputations, sequels to infections with abscesses or phlegmons, wounds drainage, etc.). • Because of its antibiotic action, it may be used on infected or infection- prone injuries, whether with little or significant exudation (pyoderma, erysipelas, etc.).

• On foul-smelling injuries, such as tissular necrosis, fungating tumors or gravitational ulcers, it eliminates the odor.

• Treatment of ectoparasites like scabies; certain mycosis reactive to the composition, and the initial form of herpes infection.

• On dermatoses: psoriasis, eczemas, dehydrosis, acne, rosacea, seborreheic dermatitis, diaper rash, excoriations, impetigo, scabies. • Gynecologic pathologies such as candidiasis, vulvovaginitis, etc.

• Proctologic pathologies such as hemorrhoids, itching, anal fistula, etc.

Case reports

With these reports, we attempt to evidence the activity of the composition of the present invention.

Case 1 (see Case Picture No. 1)

The patient is a 55 year-old male. He is a builder.

He has type 2 diabetes and suffered a 3-fragment fracture of right humerus, which produced a significant hematoma. This hematoma was infected due to a urinary tract infection. The causing bacteria were Escherichia coli (E-coli). The general condition of the patient was seriously compromised (sepsis episodes), so it was decided to carry out a surgical drainage of the hematoma.

By means of two incisions on his arm, a large amount of hemopurulent fluid was drained. Drainage incisions were cured with Furacin gauze for approximately two weeks. At this point, the treatment with the composition was started through occlusive dressing every 48 hours. Treatment continued until the wound was completely closed.

The patient received proper antibiotic and orthopedic treatments. There were no complications or adverse reactions to the composition.

Regarding what we observed on this case, we may highlight the following: 46

16

The restoration process of the surgical wound was achieved within a period of time that would be considered normal for a wound on a healthy person, with no concurrent pathologies. We must consider that our patient showed diabetes, infection, abundant suppuration of the wound and a compromised immunologic condition as aggravating circumstances for normal healing processes.

These curative treatments were carried out in spite of the fact that during the first period the purulent exudations of the wound continued, since these did not alter the consistency of the composition or its antibiotic, fibrinolytic and wound- healing pharmacologic activity (Note: diabetic patient, with a suppurant osteomyelitic focus, with wound exudation and sphacelus).

The patient did not show any adverse effects or any kind of interaction with the basic systemic medication provided (antibiotics and analgesics).

The patient was discharged and, surprisingly, much earlier than expected.

We would also like to highlight that the composition has a convenient dosage form and an easy, painless application facilitating treatment adherence.

It is of paramount importance pointing out that excellent results were obtained in this case: both wounds were closed; even when the clinical condition of the patient was considerably severe, with a negative prognosis, compromised limb viability, and even risk for his life.

Case 2 (see Case Picture No. 2)

The patient is a 58-year male who has suffered from type 2 diabetes for 30 years now. He is currently under insulin treatment.

The patient was hospitalized due to an abscess on the internal malleolar area in his left ankle, which he had had for three weeks, of uncertain etiology.

Treatment was started with proper parenteral antibiotics and a surgical drainage was performed through two incisions on the abscess fluctuant area.

The first curative treatments were performed with Furacin gauze. Previous flush with physiologic solution was applied. Then occlusive dressings with our composition were applied every 48 hours. Once the clinical condition improved, the patient was discharged, but local curative treatments continued with the same frequency. Oral antibiotics were prescribed. In this case, we find one of the examples of wounds explained in the introduction:

There was a change in the local physiological variables, causing ischemia, stasis and hydrostatic pressure increase on the affected area, which contributed to devitalize and necrotize tissues around the injury.

The above described process led to the formation of an ulcer that compromised the dermo-epidermal area, and with sphacelus in its interior. This, in turn, led and contributed to delaying or even stopping the wound-healing process. In addition, we should consider the local toxic-infectious status and the compromised immunologic condition of a diabetic patient; both factors contribute to delaying the scar-formation process.

Using the claimed composition, with no need for surgical treatment, but with physiologic solution flushes, the chemical debridement of the sphacelus was achieved. The edges of the wound started to contract and the granulating tissue started to appear progressively, even though this was a full-thickness cutaneous wound.

We may conclude that, although epithelization was not complete, since this would have demanded a longer treatment, the granulating tissue obtained was of such a good quality that it may be used for an eventual cutaneous graft to stimulate the wound final restoration.

There were neither complications nor adverse reactions during treatment.

Case 37 (see Case Picture No. 37)

The patient is a 4-year-old female with an injury on the Achillean region of the left heel, caused by trauma by a bicycle-spoke. Treatment began approximately 48 hours after the accident, applying occlusive dressing with our composition every 48 hours until complete healing. There were neither complications nor adverse effects.

Bicycle-spoke trauma is a very frequent injury in pediatric emergency rooms. The child's foot was trapped between the bicycle fork and spoke, causing foot torsion, with shearing effect on the soft parts and the bone. This shearing usually results in dermis vessels injuries, which produces a skin eschar. According to the seriousness of the process, healing may take almost a month. In this case, it is worth highlighting not only the objective side of healing, but also the "subjective" side.

For those who have been on the area of general healing in any medical center, particularly in a pediatric room, there is a situation which is especially hard to deal with. We are talking about the fear and anguish that overcome the patient when the time comes to detach the gauze from the wound: will it be stuck?

We know too well that detaching a "stuck" material from the exposed tissue bed of a wound causes pain. Pain leads to crying, screaming, struggling, etc., complicating our job as doctors, and even making doctor-patient relationship even harder.

By using this composition, we have observed that in the case of curative treatments in which the material (gauzes, dressing, bandages, etc) is left for more than 48 hours, by moistening it with physiologic solution, it is very easily detached with a soft pressure, without causing serious discomfort or pain, and avoiding the abovementioned complications.

The picture is eloquent, "it earns the patient's trust".

Case 10 (see Case Picture No. 10)

The patient is a 68-year-old male, with Type 2 Diabetes. Due to bad progress of injuries on his foot, which had not benefited enough from conservative treatment, and complicated the patient's general condition, an infracondyloid amputation on his left leg was performed. The usual technique was used, leaving a viable stump for future collocation of prosthesis to walk.

There was dehiscence on an amputation stump area, with retraction of the wound edges, sphacelus in its interior and delay in the wound-healing process.

Curative treatments started by means of occlusive dressing with our composition every 48 to 72 hours, until the wound was completely healed. There were neither complications nor adverse effects.

In this case we find an injury that, unfortunately, is very frequent in this type of surgeries, whether due to diabetic or vascular causes.

Dehiscence of any sector of the surgical wound, with posterior retraction of the wound edges, sphacelus and infection, delay stump cicatrisation. This damages the patient, since it delays the collocation of walking prosthesis, and therefore, also delays the patient's return to his daily activities (work, family, etc.).

While we can observe that the amount of affected tissue does not seem to be significant, the most important aspect in this kind of injuries is the "quality" of the tissue.

In the case of diabetes, we are talking about tissues that are affected in their nerve stimulation (diabetic neuropathy) and in their circulation (diabetic angiopathy); both conditions that alter normal tissue healing process.

Notwithstanding the abovementioned, we realized that by using the composition on a regular basis (curative treatments every 48 to 72 hours), it was possible to stimulate granulating tissue after dermo-epidermal regeneration and complete injury healing.

Case 8 (see Case Picture No. 8) The patient is a 56-year female, with Type 2 Diabetes. She presented neuropathic diabetic foot, showing necrosis on the second toe of right foot, non- recoverable by means of conservative treatment. A second toe excision and half metatarsal were performed according to proper amputation technique.

After 24 hours, dressings were applied with the composition of this invention every 48 hours. After approximately 15 days, the patient was discharged. Stitches on metatarsal area were removed and we observed dehiscence on surgical wound edges with abundant sphacelus in its interior. However, we continued with the same treatment plan until complete wound closure.

On neuropathic diabetic feet, toe injuries are very frequent. Generally, a simple wound caused by trauma, rubbing, burns, etc., which is not timely diagnosed, causes complications. This may begin with the amputation of a toe, and in many cases result in leg amputation.

In this case, even though only the toe and half metatarsal were excised, there were complications which altered the normal course of the healing process. Dehiscence of stitches and the presence of devitalized tissue remains gave rise to formation of significant sphacelus on wound bed. As we said in the introduction, this constitutes a key factor in wound-healing delay. Notwithstanding the abovementioned, with regular use of this composition, antiseptic flushes and without any debridement surgical procedure, we achieved formation of granulation tissue, epithelization and wound closure, with neither complications nor adverse reactions, in a considerably short period of time.

Case 9 (see Case Picture No. 9)

The patient is a 69-year-old male, retired, with Type 2 Diabetes. Two years ago he underwent infracondylar amputation on lower right limb. There is necrotic eschar on the hallux distal region of the left foot and a second smaller eschar on dorsal face of fourth toe of the same foot.

Hallux injury progresses unfavorably, with increasing necrosis area, so it was decided to disarticulate it. Dressings with the composition were applied every 48 hours on the surgical wound bed and also on the fourth toe eschar. As the necrotic process progressed on that toe, compromising half of the foot, it was decided to perform surgical disarticulation. Regardless dressings, antiseptic baths and proper antibiotic treatment, evolution on surgical wounds was unfavorable, and the necrotic process compromised up to midfoot.

For these reasons, we decided to amputate at transmetatarsal level, according to proper surgical technique. This technique consists, basically, on performing the surgical cut at the middle part of the five metatarsals, excise the back of the foot and extract it all together. A plantar flap was left, which is folded and used to close the surgical tissue bed, forming the corresponding stump.

As of the fourth day after surgery, a blue-black color began to appear on the area where the plantar flap was stitched to the back of the foot. Said area grew progressively and gradually (vascular necrosis) leading even to dehiscence of a wound sector with sphacelus and necrobiosis on the edges. The necrotic process progressed at a constant pace, as well as stump tissular deterioration. This increased the likelihood of a possible stump infection and eventual complication of the remaining healthy foot. This situation led to a new surgical decision, which was taken not over scientific orthodoxy, but on the experienced stemming from the results obtained using the claimed composition. A "recovery" technique was performed, which consisted on drying only the devitalized and necrotic tissue on the stump, with no action performed on the vital and bleeding tissue.

Tissue bed was filled with the composition and we waited for the possible appearance of granulation tissue, and wound-healing process. After a week, and applying occlusive dressing with the composition of this invention every 48 hours, we were able to observe some results.

Wound edges retracted, granulation tissue began and gradual appearance of epithelium could be observed. At the moment of this presentation, the patient continued with treatment and kept on improving.

During this patient's treatment, we made some observations about the composition that we consider relevant:

On surgical wound caused by hallux disarticulation, there were no signs of infection or necrosis, but neither granulation nor epithelium tissue developed.

On wound caused by disarticulation of fourth toe, there was devitalized tissue that showed no response.

It was on the exposed tissue bed of the stump wound where granulation tissue was gradually generated, and then epithelium began to form on the wound edges.

The patient's foot color before amputation was bluish (cyanotic) when the limb was lowered (due to circulatory insufficiency); but this phenomenon was no longer observed after progressive formation of granulating tissue.

That is to say, even when the foot was lowered, skin tone remained normal, with no signs of cyanosis.

We attribute these phenomena to the formation of granulating tissue which was very active at a vascular level, which compensated the pre-existent circulatory deficit almost entirely.

During treatment, there were neither allergic reactions nor infectious complications. The patient did not receive additional antibiotics. Case 15 (see Case Picture No. 15)

The patient is a 69-year-old male. Type 2 Diabetes. Around four years ago, he underwent infracondylar amputation on his lower left limb.

He developed necrosis on first, second and third toes of the right foot, which did not respond to conservative treatment.

Due to patients' refusal to an infracondylar amputation, we decided to amputate at metatarsal level of the affected foot (2003).

Firstly, the exposed tissue bed was treated with antibiotic and fibrinolytic unguent during four months, with no favorable results. No significant granulating tissue formed during that period. It was decided to begin treatment with our composition. This treatment continued for two months until complete wound- healing. During this treatment there were neither complications nor adverse reactions.

Case 11 (see Case Picture No. 11)

The patient is a 71 -year-old male, with Type 2 Diabetes, showing necrosis on first, second and third toes of the left foot, compromising the midfoot tissue (naturopathic-vascular diabetic foot). The condition remained irreversible with conservative treatment. Due to patient's refusal to an infracondylar amputation, it was decided to perform an amputation at midtarsal level of the affected foot.

While he was hospitalized, as from the second day after surgery, dressings with the claimed composition were applied every 48 hours. Once he was discharged, dressings were applied every 72 to 96 hours until complete injury healing.

No antibiotic treatment was indicated while he was discharged since he presented no additional infections or any other secondary complications. Due to serious family issues, the patient could not rest properly, glycemia controls were not performed and he was not able to follow the diet as indicated; however, wound evolution was always favorable.

After five months, he had to be hospitalized due to thrombophlebitis on the affected limb, but nevertheless, there were no complications on the surgical wound. We consider that from all the examples stated so far, these cases describing amputations deserve special consideration, from the medical point of view, as well as the therapeutic and pharmacologic action of the composition.

Amputation levels were chosen according to a "recovery" criterion. That is, making all efforts to preserve the distal level of amputation and the affected limb as much as possible, (please remember that on two cases the patients already had amputations on contralateral limb).

"Tarsometatarsal and intertarsal amputations are mentioned just for reference. Cutaneous grafts on traumatic amputations at the levels mentioned above are especially prone to be destroyed. The most common final result is progressive deformation in clubfoot (hyperextension of ankle articulation), with ulceration of the inferior bone edge. Patients with cutaneous grafts show repeated ulcerations on the grafted areas". (Duvries-lnman Foot Surgery 5° publication, pages 525-527). However, during therapeutic treatment, wound-healing repair stages were developed from the surgical tissue bed.

Significant granulating tissue was generated, which progressively covered muscles, tendons and bones, also the wound edges contracted and the epithelial layer developed gradually, covering the wound. There were no infectious complications; the generated tissue was viable, with no necrosis or allergic reactions.

We also observed that the healing stages occurred in order and progressively, following the natural order of the repair process (even when they were patients with pathologies that altered the wound-healing process, e.g.: Diabetes).

Without hasting a theory, we suppose that improvements obtained with the claimed composition were probably due to growth factor stimulation, an effect that we consider as the "biological activity" of the composition.

Case 14 (see Case Picture No. 14)

The patient is a 70-year-old male, with Type 2 Diabetes. He underwent a hallux and first metatarsal amputation on his left foot due to irreversible necrosis (2005). The wound was treated with the composition and after three months it was completely healed.

In this case, the amputated area was anatomically and functionally important for normal foot support. A considerable amount of tissue (soft parts and bones) was removed but there is no invaginated or retractile scar, due to strong generation of granulating tissue that filled the surgical wound.

Proper shoes and insoles were prescribed, but the patient was not able to afford them, so he used regular sport shoes.

In spite of this, except for a tissular hypertrophy on his internal arc caused by bad posture (leaning), there were no complications on the cicatricial tissue obtained.

Case 13 (see Case Picture No. 13)

The patient is a 61 -year-old male, with history of Type 2 Diabetes. He has neuropathic foot, with severe lymphatic disorders. First and fifth toe were amputated.

His bad posture caused pressure sores on the metatarsal region (plantar mal perforant). He was treated with our composition and a proper insole was prescribed. In this case, apart from his base pathology (diabetic neuropathy), he had lymphatic circulatory disorder with limb chronic edema and the abnormal leaning of the foot sole (aggravated by first and fifth toe amputations). In addition, due to family and labor issues, the patient was not able to rest as indicated.

Nevertheless, even though plantar mal perforant is a severe injury, we observed favorable evolution. Neither complications nor adverse effects were observed.

Case 23 (see Case Picture No. 23)

The patient is a 65-year-old female, with history of Type 2 Diabetes and cardiac insufficiency. She shows an ulcer on the inferior third cubital edge of the right forearm. Said ulcer had approximately a surface of 10x6 cm and went deep compromising up to muscular and tendinous levels. There were some areas covered by necrotic tissue. This injury was nearly 3 weeks old and, according to the patient, it was caused by a substance introduced by venoclysis when she was hospitalized due to a decompensate heart failure. At that time, she received treatment with silver sulfadiazine, with little response to formation of granulating tissue and it was necessary to remove the necrotic tissue by surgery. We started to apply occlusive dressings with the composition of present invention every 48 hours, with favorable evolution. As the picture shows, the ulcer edges contracted and granulating tissue began to develop.

Our treatment lasted approximately 20 days, until the patient had to be hospitalized due to a cardiac complication, interrupting the healing follow-up. In this case we would like to point out that, even though the patient was treated with other wound-healing creams for three weeks, there was very little response. During the time she was treated with this composition, we observed favorable wound evolution, although the patient had an underlying disease (Diabetes) delaying the healing process and favoring infection. During the follow-up carried out two weeks after the beginning of our treatment, the foregoing biological activity began to appear: contraction of wound edges and formation of granulating tissue. This showed a clear evolution of the cicatricial process, compared with prior treatment with other creams.

Case 39 (see Case Picture No. 39)

The patient is an 84-year-old male, who suffered trauma from falling. He showed ulceration on the back of his right hand. We applied occlusive dressings with the claimed composition every 48 hours

During the follow-up performed 7 days later, there was wound contraction and re-epithelization. After 14 days, the injury was completely closed.

It is important to highlight that although the patient was old, (skin senile atrophy typical of such age) the wound healed in a very short time. Neither complications nor adverse effects were observed.

Case 31 (see Picture Case 31)

The patient was a 4-year-old male, brought to consultation by his mother. He showed cutaneous injuries in the abdomen, lumbar region, gluteus and nape, constituted by secreting erythematous plaques containing blisters, some without crusts, some with yellow crusts, excoriations due to scratching and pustules, showing characteristic symptoms of pyodermatitis. Oral antibiotics were prescribed and topical treatment with the composition of this invention every 48 hours was applied. In approximately 2 weeks, resolution of injuries as well as wound healing was observed.

This case shows the wound-healing effect and antibiotic properties of the composition.

Case 32 (see Picture Case 32) The patient is a 69 -year-old male. He presented pyoderma symptoms on right forearm and wrist. He showed blister-like injuries, some without crusts, and some with yellow crusts, both self-inoculated by scratching, which he had had for approximately 1 week. The treatment consisted of oral antibiotics and topical application of the claimed composition. After 48 hours the wound showed some improvement, and after a week it was completely closed.

Pyoderma as well as impetigo, are infectious injuries highly contagious that usually manifest on young children but less frequently on adults. Group A streptococcus is the most common responsible microorganism. Overcrowding, deficient hygiene and untreated minor cutaneous traumas contribute to disseminate infections among family members.

In this case, we observed the composition antibiotic and anti-inflammatory properties leading to the control of the infection as well as the itching. It also results in stimulating injuries re-epithelization due to its dermatotrophic effect.

Case 33 (see Case Picture No. 33)

The patient was a 9-year-old male, showing pruriginous injuries on both hands which he had had for 15 days. The injuries were vesiculose and desquamative. Both these injuries and fissures were found on an erythematous basis, predominantly on the fourth finger of his right hand and the third finger of his left hand. These injuries were compatible with dehydrotic eczema. Treatment began with occlusive dressings with the disclosed composition every 48 hours. There was a rapid improvement and the case was solved one week after beginning treatment.

Dehydrotic eczema is an allergy-based disorder that affects palms, soles and the sides of fingers and toes, manifested by vesicular-like or blister-like injuries, usually pruriginous.

The patient had received prior topical treatments with different creams (mid- potency corticoids, lotions with silver sulfadiazine) with no improvement.

Although it is well known that agents other than maximum-potency corticoids are ineffective against this condition, in this case we could observe a favorable evolution due to the anti-inflammatory and anti-pruriginous effect of our composition.

Case 38 (see Case Picture No. 38)

The patient is a 13-year-old male, healthy, with no relevant pathologic history. He shows an ulcer on the mid-third region of the anterior face of his left leg caused by a sharp metallic object. Said injury showed substance loss and signs of infection. Oral antibiotics and the application of flat dressing with the composition of this invention every 48 hours were prescribed. The evolution was positive and the injury was healed after 2 weeks. In this case, once again, both the cicatricial and antibiotic effects of the composition were proved.

Case 3 (see Case Picture No. 3)

The patient is a 67-year-old male, retired, with a history of Type 2 Diabetes. Neuropathic diabetic foot, showing plantar mal perforans ulcer on the head of the second metatarsal, on his right foot.

In 2005, he underwent an amputation of the second ray due to toe necrosis and osteomyelitis.

Treatment of the plantar ulcer started by applying occlusive dressings with the disclosed composition every 48 hours. Concurrently, a plantar orthosis was prescribed for mobility purposes. There is a progressively favorable evolution with epithelization of wound edges after an approximately one-month treatment. Treatment continued until almost complete healing after four months.

During treatment there were no local complications and there was no need for systemic treatment with antibiotics.

Although the patient had to rest for some time, his ability to walk was not significantly affected.

Within peripheral neuropathies, especially those of neuropathic diabetic foot, plantar ulcers represent a problematic situation for current therapy. Since these injuries compromise the anatomy of foot leaning structural tissues, spontaneous healing is impossible. This situation determines a serious prognostic for the patient's walking functionality and dynamics if such injuries are not properly diagnosed and treated. These injuries that, at the beginning, affect the epidermal tissue may go deeper, compromising bone tissue. In addition, infections may aggravate the original condition, and in some extreme occasions, it may be required to amputate the affected limb. In conclusion, we may say that we are facing an injury with a multiple etiology: a mechanic injury caused by constant pressure while walking on a tissue biologically altered by neuropathic trophic disorder, determining a degenerative tissular injury of torpid evolution. From the foregoing, it is clear that this pathology requires difficult and complex treatment. However, with this composition and a proper orthosis, we observed that both compromised tissue growth and the injury closed in a very short period of time with. No serious complications were observed.

Case 6 (see Case Picture No. 6)

The patient is a 52-year-old male, gardener, with history of Type 2

Diabetes. Neuropathic diabetic right foot, showing a large abscess compromising the plantar area of the heel nearly up to midfoot, ulcered, with dermal-epidermal compromise, and foul-smelling purulent secretion. It possibly derived from a traumatic injury caused while working.

During the time he was hospitalized, toilet and surgical drainage were performed with parenteral antibiotic treatment. After surgery, the treatment included antiseptic baths and occlusive dressings with the composition. Once the patient was stable, he was discharged. Occlusive dressings every 48 hours in outpatient facilities were applied until complete healing.

In this case, we are dealing with a mechanic injury on dystrophic tissue (diabetic neuropathy), causing an injury and plantar mal perforans on an area of structural importance for foot leaning.

By using the composition of the present invention together with a additional antibiotic treatment while he was hospitalized, we observed that the wound healed relatively fast.. No adverse effects were observed. It showed good tolerance to the composition, remission of infectious focus and total foot functionality recovery, enabling a rapid return of the patient to his daily activities.

Case 5 (see Case Picture No. 5)

The patient is an 82-year-old female with no history of relevant pathologies. She has an ulcerate injury on the heel, of an unclear etiology, probably of traumatic origin and of approximately 6 months-old.

She received treatment with creams and wound-healing compositions but the injury did not heal.

We began to treat her with occlusive dressing with the claimed composition every 48 hours, without systemic treatment. The patient did not rest for long periods. There was epidermal tissue development and the wound closed approximately 7 weeks after the treatment started, with no complications, good tolerance and in a short period of time.

Once again, this treatment was successful where other wound-healing treatments commonly used nowadays were not.

Case 4 (see Case Picture No. 4)

The patient is a 37-year female, with history of Type 2 Diabetes. She has an infectious process on the hallux metatarsal phalangeal joint on her right foot, which was surgically drained and the proper antibiotic treatment was completed. During treatment, she develops a mal perforans ulcer on the leaning area of the first metatarsal head, of full thickness. We began treatment directly with occlusive dressings with the composition of this invention every 48 hours and continued with oral antibiotics until both injuries were healed. In this case, we did not use any other wound-healing products. We would like to highlight the dermatotrophic effect of the formula, as well as its antibiotic effect on this injury of degenerative and infectious etiology. We observed epithelization after a 15-day treatment, and complete wound closure after 40 days, approximately.

Case 29 (see Case Picture No. 29)

The patient is a 50-year-old male with no history of relevant pathologies. He showed a superficial second-degree burn on the back of his right hand (caused by fire). This burn compromised a great portion of his hand and five fingers, causing functional impossibility since the patient is right-handed.

Dressings with the disclosed composition were applied every 48 hours, showing good evolution with almost complete epithelization after 10 days. Neither complications nor adverse effects were observed. The patient stated that he started feeling less pain after the first treatment.

Case 28 (see Case Picture No. 28)

The patient is a 19-year-old male with no relevant clinical history. He showed burns and bruises on left inferior limb due to a fuel tank explosion. The patient had superficial second-degree burns, with large denuded areas of erythematous base, painful, and with large hematoma and edema, due to contusion with hot metal splinters produced by explosion.

Dressings with our composition every 48 hours were applied covering the area with sterile bandages. The patient had a favorable progress, with noticeable improvement after one week and epithelization after two weeks. Neither local complications nor infections were observed.

As we know, skin thermal injury may vary from superficial damage to severe and extended skin loss, which results from contact with heat, hot liquids, chemical agents or other physical agents such as ultraviolet or infrared light. In adults, most common burns are caused by fire, while in children burns are usually caused by hot liquids. Tegument burn causes cellular death, different grades of capillary injury and protein coagulation. Capillary injury manifests by an increase in permeability. This phenomenon occurs around the burn and also in areas away from it. This causes organic fluids (plasma and electrolytes) to be retained in extracellular spaces, added to organic fluid loss through the wound and superficial water evaporation.

The severity of these disorders is directly related to burn extension and depth.

We must bear in mind that, under ordinary circumstances, even minor burns may be severe or even fatal (mainly for older people or small children), In addition, ischemia as well as infection may turn a superficial burn into a deeper full-thickness burn.

Due to the aforementioned, and to the pain and functional disorders caused to patients, we consider that it is extremely important to find a treatment that controls infection, leading to rapid epithelization of these injuries. Using the claimed composition, we achieved the healing of injuries, in spite of their two-fold nature (contusive and abrasive) in terms described in literature for superficial burns and without added complications (infectious processes).

Case 30 (see Case Picture No. 30) The patient is a 24-day-old male baby, brought in by his mother due to severe napkin rash, probably resulting from irritation, approximately 15 days old. During physical examination, we observed erythema compromising penis, scrotum, groins and perianal area skin, with small papules. Perianal area was the most compromised, with significant erythema and erosions. The child was irritable and according to his mother his feeding and sleeping habits had been affected.

The patient had received different topical treatments with triple-action creams (combination of antibiotics, corticoids and antimycotics) and wound- healing powders with no response and progressive aggravation of the symptoms. We began to treat the child with the disclosed composition twice a day. His mother observed some improvement on the injuries as well as on the child's mood after 48 hours. During the first follow-up, after a week, there were clear improvement on injuries and complete healing after fourteen days (second follow- up visit). 46

32

In this case we have an injury of chemical origin, i.e. constant irritation caused by urine and feces on the skin of an area almost permanently occluded by the napkin, leading to an increase in temperature and dampness, and greater penetration of chemical substances to the skin. Due to significant histotrophic, anti-inflammatory and anti-infectious effect of the composition of present invention on different injuries, we observed favorable evolution, with no secondary effects and good tolerance, on short term treatment.

We would like to highlight the success of this treatment where others had failed.

Case 36 (see Case Picture No. 36)

The patient is a 16-year-old female, with Grade Il inflammatory acne, after three years of evolution. She received several topical treatments (antibiotics) with little response. We started treatment with the disclosed composition on a daily basis with good response in just a few days.

Acne vulgaris is a disease that affects hair follicles, mainly during adolescence.

Most cases are pleomorphic and show a wide variety of injuries such as comedones, papules, pustules, nodules and scars.

Although the original cause of acne is unknown, there is considerable information regarding factors related to its pathogenic factors. It is a condition with multiple causes that develops on sebaceous follicles.

The primary change is a disorder on the keratinization pattern of the follicle. Patients with acne have bigger glands and produce more sebum than people without acne.

Free acids as well as substances produced by microorganisms (protease and hyaluronidase enzymes) may be significant for the inflammatory process. Predominant microorganism is the Propionibacterium acne, which also secretes chemotactic factors that attract polymorphonuclear leukocytes and stimulates classic and alternative pathways of complement, probably contributing to inflammatory response. We may consider that in this case, this composition acted due to its antiinflammatory, antibiotic and cutaneous regenerator effects.

Case 20 (see Case Picture No. 20) The patient is a 77-year-old female, with venous ulcer with an evolution of approximately 5 months, located on the anterior face of the inferior third of the right leg.

She has a history of high blood pressure with ischemic episodes on the central nervous system, and venous disorders on inferior limbs. The patient underwent some topical treatments with wound-healing creams and oral antibiotics, but without response.

She came to consultation after being hospitalized due to an infection around the injury for which oral antibiotics were prescribed.

We began treatment with occlusive dressings with the claimed composition every 48 hours until complete closure of the injury.

During follow-up, we observed the formation of granulating tissue, covering sphacelus and the whole injury surface, then re-epithelization and finally the complete closure after 4 months, approximately.

We would like to take this case as an example, since we were able to follow it up until its conclusion. The other cases consisted of long lead chronic injuries, so we were not able to observe them from the beginning to the complete closure of injuries.

Chronic ulcers, some of them largely extended, on areas with circulatory disorders, with severe tissular compromise, treated with topical and systemic treatments with little or no response at all.

It is our goal to prove that, due to its biological activity, by using this composition on a regular basis, it is possible to observe contraction on the ulcers edges, significant formation of granulating tissue and re-epithelization. A considerable decrease in the injury size and infection control were also observed. With this treatment it is also possible to prepare the patient for other medical or surgical treatments (grafts, tissue cultures, Unna's paste boot, phlebologic treatments, etc.). Case 21 (see Case Picture No. 21)

Female patient with history of asthma, psoriatic arthritis, lung fibrosis, high blood pressure and hypothyroidism (Hashimoto's Thyroiditis). She received treatment with high dose of systemic corticoids for many years, due to her base pathologies, which led to iatrogenic Cushing's Syndrome, with subsequent cutaneous disorders (atrophy, striae, capillary fragility, wound-healing disorder, etc.).

The patient suffered trauma on her left knee with transversal infrapatellar blunt force cut wound, on bending area, which was sutured. While removing stitches, there was dehiscence of part of the wound, the edges retracted producing an ulcer with internal sphacelus, and wound-healing delay.

Treatments with other ointments, creams and antiseptic baths were tried, but no response was produced.

She came to consultation because the plastic surgeon recommended a skin graft. Treatment began with regular dressings with the composition of the present invention every 48 hours. She did not receive any additional treatment, whether systemic or topical, and she did not rest as indicated.

The patient showed favorable evolution, with dermal-epidermal regeneration, formation of granulating tissue, retraction of wound edges and complete healing in a very short term. Neither complications nor adverse effects were observed.

In this case, it is worth highlighting the diverse concomitant pathologies of the patient, which together with corticoids, were significant in wound-healing process delay. However, the biological activity of the claimed composition was proven as the injury healed within a normal period of time. No adverse reactions were shown and it prevented wound infection, which is very frequent in these cases.

Cases 16, 17, 18, 19, 22, 24 and 26 (see corresponding pictures) These cases represent examples of ulcerations on inferior limbs with different etiology (lymphatic, venous, arterial), all in different stages of evolution, which have been treated with the disclosed composition. As it can be seen, the generation of granulating tissue was obtained, which sometimes served for injuries healing, and some other times, served as a basis for eventual collocation of cutaneous grafts.

Within the category of "external" injuries with tissue loss, ulcers on inferior limbs have historically been a problem in medical therapeutics, and still are. There is a long list of drugs and procedures that have been used to present times to heal these injuries.

Evidently, "external" ulcers are the expression of an "internal" problem

(especially venous, lymphatic or arterial circulation disorders), which will manifest either as acute or, more frequently, as chronic, Therapeutic experience showed us that many injuries become chronic not only because of internal conditions, but also, frequently due to lack of therapeutic efficacy of products used during the acute stage.

Briefly, the cases presented as examples show that the new composition of the present invention has acted on acute injuries generating granulating tissue and healing them. On chronic injuries it has progressively generated granulating tissue which favors the healing or the eventual collocation of cutaneous grafts.

Case 12 (see Case Picture No. 12)

The patient is a 71 -year-old male, with Type 2 Diabetes, under treatment with oral hypoglycemic agents.

He showed suppurating interphalangeal septic arthritis of the fifth toe of his right foot, which caused destruction of the joint regardless proper antibiotic treatment. It was decided to disarticulate the affected toe, by means of regular surgical technique. Dressings with the claimed composition were applied on the wound exposed tissue bed every 48 hours.

The surgical wound healed. No complications or adverse effects were observed.

Case 7 (see Case Picture No. 7)

The patient is a 65-year male, with Type 2 Diabetes and treated with oral hypoglycemic agents. He showed a blister-like injury on his right foot second toe pulp. Since it is a neuropathic foot with lack of sensibility, it was secondarily 8 002346

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infected, and the viability of the affected toe was compromised. Proper antibiotic treatment was prescribed as well as dressings with the composition of this invention every 48 hours. There was a positive response to prescribed treatment, obtaining injury epithelization and the preservation of the affected toe.

Case 25 (see Case Picture No. 25)

The patient was a 63-year taxi driver with Type 2 Diabetes. He showed dermal-epidermal ulcer on the right foot (neuropathic foot) hallux metatarsal- phalangeal area. The injury was approximately one month old. He had received treatment with other wound-healing products but there had been no improvement.

Dressings with the composition of the present invention every 48 hours were applied as well as strict rest. The injury healed. No adverse reactions or side effects were observed.

These cases are examples of a very frequent injury on vascular neuropathic foot; it is usually caused by footwear "rubbing". This injury starts with a small dermal-epidermal ulcer, unnoticed because of the patient's lack of sensibility. The ulcer increases in size and many times results in complications, with added infection that may compromise the area circulation, inducing necrosis.

In practice, it is frequently observed that ulcers that have not improved, in acute condition, are prone to necrotize, since cicatricial epithelium stimulation in its natural biologic form is altered on diabetics patients (due to lack of nervous and vascular stimulus).

However, these examples show that the biological activity and cicatricial selective stimulation of the claimed composition have been proven.

Case 34 (see Case Picture No. 34)

The patient is a 47-year-old female with no history of relevant pathologies. She showed reddish papules covered by silver-white micaceous squamae, symmetrically distributed on both elbows. She manifested itching and burning sensation, which was compatible with psoriatic dermatosis. After a three-month treatment with the composition of the present invention, we observed that the psoriatic dermatosis improved. No corticoids were used during treatment. T/IB2008/002346

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Case 35 (see Case Picture No. 35)

The patient is a 65-year-old male with no history of relevant pathologies. He showed an erithematous area with vesicles and desquamation on the external lateral area of his left foot, from the heel to the fifth toe. He described occasional episodes of intense itching. The symptoms were compatible with eczematous dermatosis. After a three-week treatment with the disclosed composition, there was some improvement. During treatment no corticoids were used.

We could frame the cases presented above (dehydrosis, eczemas and psoriasis) within "dermatoses". These specific or non-specific inflammatory affections may compromise the epidermal layer as well as the dermal-epidermal layer.

As shown in the examples above, and as it was described in the title, we have revealed the stimulation effect on the dermal-epidermal normal trophism of the new composition of this invention. It is worth highlighting that, in conventional treatments, these pathologies are treated with high doses of corticoids, and we have not used any, proving the anti-inflammatory effect of this composition.

Through the cases stated as examples we tried to prove the biological, cicatricial and dermal-epidermal normal trophism stimulating activity of the claimed composition.

CONCLUSIONS REGARDING CLINICAL CASES

From the experience obtained using the composition of the present invention, the following advantages have been observed: 1- The composition was topically used on dermal-epidermal injuries. The etiology of these injuries included multiple factors (traumatic, infectious, degenerative, etc.).

2- In all cases we observed positive results, whether total healing or substantial improvement of injuries. 3- On infectious, inflammatory and degenerative injuries we observed improvement, probably due to its anti-inflammatory, anti-infectious and tissue regenerative effects (See Cases 31 , 32, 33, 34, 35 y 36). 002346

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4- According to patients, on first-degree and second-degree superficial burns, pain was relieved approximately 30 minutes after the first dressing of this composition was applied.

5- On injuries with tissue loss or with loss of tissue continuity (surgical or traumatic wounds, ulcers, complicated or simple burns, chronic or acute), we noticed healing or improvement from stimulation of the granulating tissue, due to a strong angiogenic effect that accelerated wound-healing and re-epithelization processes. These processes have developed gradually and progressively, following, on most cases, the normal stages of cicatrisation (inflammatory, proliferative and repair), even under adverse healing conditions (secretions, sphacelus, infection, etc.). (See Cases 1 to 30 and 37 to 39).

6- Our assumption is that the selective tissular regeneration results from stimulation of growth factors, which would lead to wound-healing biological processes. (See Cases 1 , 8, 9 and 11).

7- This phenomenon, which we may call "Biological Activity of the Composition", is the original and distinctive feature which differentiates the composition from other wound-healing products.

8- The results described above, i.e. wound healing or improvement, were obtained within timeframes that are considered normal, in spite of the fact that we were dealing with complex injuries (diabetes, infections, autoimmune diseases, vascular disorders).

9- The action of the composition was not interfered by the presence of necrotic tissue, secretions, sphacelus, etc., and it was possible to use it on healthy tissue such as bones, tendons and muscles with no manifested alteration. (See Cases 1 , 2, 8 and 11).

10- Thanks to the consistency of the claimed composition, it can be used on injuries with secretions, exudations or cellular detritus, without interference in the therapeutic action of the composition (Case 1). 11- Wound stench is an extremely painful symptom, both for the patient and his/her family environment, and it constitutes a factor of social embarrassment and significant psychological consequences. Due to its antibiotic synergy, this composition acts rapidly and effectively on bacteria that produce bad smell. 12- Results were obtained without using any additional method to treat wounds (hyperbaric chamber, ozonotherapy, physiotherapy, lymphatic drainage, podiatry).

13- Regarding the healing technique and application times, we observed: • Easy application.

• Easy removal, since gauze does not adhere to the wound (as opposed to other products currently found in the market), resulting in benefits for patients. They suffer no pain or cicatricial germinative tissue loss, and they are better predisposed to undergo curative procedures. (Case 37).

• Wide interval between doses. Due to its consistency, which is not degraded by tissular secretions, it enables the composition to remain on the tissue bed exercising its therapeutic effect. Dressings can be performed every 48 hours or more (according to doctor's criteria and wound evolution). As an example, please refer to Case 11 , where a surgical wound (midfoot amputation) was treated with dressings every 72 hours, obtaining complete healing. No added complications were observed.

14- We believe that it is worth pointing out that, due to its Lanovaseline base, this composition is especially useful for occlusive dressings, since its water-repellent capacity increases tissue hydration. These characteristics and its anaerobiosis foster granulating process during wound healing.

15- We would like to highlight that, while using the disclosed composition, we observed a significant phenomenon in wound-healing process: the contraction of the wound edges. With the composition of the present invention, this contraction effect was superior to what we observed while using other wound-healing products (Case 1).

16- Regarding adverse effects, we should mention that even though the balsam of Peru is considered as an allergenic substance, during our experience we observed no relevant allergic reactions (only contact dermatitis was reported, which was reversed using corticoids). Taking into consideration the amount of studied cases, as regards their time and number, allergic reactions were extremely low, and were treated with corticoids, allowing the patient to continue with basic treatment.

17- As the composition obtains good tissular substrata, it allows the professional to use other treatments: e.g. cutaneous grafts, tissue culture collocation, different membranes, and rehab prosthetics. From the medical point of view, especially for surgical specialists (general surgery, plastic surgery, orthopedics, etc.) who work on wounds and injuries that may generate great tissue loss or complications that result in irreversible injuries (e.g. severe trauma, open surgical wounds, complicated amputation stump, etc.), we believe that it is important to have a reliable composition capable of generating tissue. Moreover, the composition should do so in the most anatomic and physiological possible way, not only for wound-healing, but also for having some viable tissular substrata (formed tissue) in such an amount that may simplify, in size and amount, posterior surgeries. 18- This composition allows the concurrent use of systemic treatments such as therapies with antibiotics, anti-inflammatory, chemotherapy, immunotherapy, venotonics, and vasodilators.

19- Patients grow confident towards treatment and hopeful about results due to outstanding therapeutic results, easy application, and the long interval between doses. This encouraging situation, which is necessary for healing, gives rise to a very positive attitude known as "adherence to treatment". On many occasions, this attitude from the patient is hard to get during the course of chronic diseases leading to therapy abandonment and subsequent negative results.

20- Considering that the WHO (World Health Organization) has declared Diabetes as the "21st Century Pandemia", what we have experienced with our diabetic patients is particularly relevant. Diabetic patients are extremely difficult to treat and they present a complex physical pathology, many times aggravated by their psychological profile. They tend to be rebellious towards treatment and they frequently quit (e.g. they do not follow the required diet, indicated rest or do not follow up glycemia controls, etc.) They also suffer from eventual complications on their social environment (family, labor, etc.). But, regardless these adverse situations, we observed that the results obtained with the disclosed composition were positive, especially on lower limb injuries such as plantar mal perforans, amputations and ulcers. Thanks to the observed improvement, the patient "was feeling well", and began pacing before it was indicated, without relevant added complications that could lead to therapeutic failure.

In reference to the obtained results, we consider that this composition may be a valuable contribution to the treatment of diabetic pathologies in lower limbs, since its use diminishes the painful consequences suffered by these patients.

As a conclusion, we would like to highlight the following benefits: A- From the social perspective: due to rapid and favorable results, patient's hospitalization and treatment periods are shortened. They are able to return to their family and work environment sooner.

B- From the economic perspective: case descriptions show that the advantage is twofold: on the one hand, healing supply cost is diminished; and on the other hand, complications arising from transportation also decrease

(ambulances, taxis, etc.) due to the broad interval between doses.

C- Since it is a composition with a multipurpose therapeutic activity, it is recommended for institutional use (hospitals, clinics, geriatric nursing homes, rehabilitation centers, etc.). D- This means that we can treat pathologies of infectious, degenerative and traumatic etiologies with only one composition, with no need for a particular product for each injury.

"Surprisingly" to us as professionals and also to our patients, we found out a combination that leads to results exceeding everything known so far, since the formula combines active ingredients required to treat all the injuries described above. Moreover, this composition offers easy application, good tolerance and easy elaboration; it eliminates bacterial contamination, detritus and bad smell, facilitating wound-healing, which has improved the cost-benefit ratio for the patient. It has proved to be a very useful tool in healing centers, emergency rooms and wards, obtaining complete closure or significant improvement on many common injuries in daily medical practice. 2008/002346

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DENTISTRY

COMPOSITION USAGE:

We will describe pathologies on which the composition of the present invention has been used in the field of dentistry. We used the claimed composition in dentistry, both at private and public level, considering some of its inherent advantages: A- Shorter healing time B- Less expensive C- Easy to handle D- Plasticity

USES IN DENTISTRY: The composition was used in: 1- Root Canal (endodontic) treatments 2- Periapical infections

3- Periodontal diseases

4- Stomatology

1- ROOT CANAL (ENDODONTIC) TREATMENTS It is prescribed when there is an infectious, inflammatory or traumatic process compromising pulpal tissue (the soft part of the tooth, rich in blood vessels and nerves). Endodontics deals with etiology, diagnosis, prevention and treatment of pulpal disease and its complications.

We observed that using this composition leads to the formation of a biologic material from the periapical connective tissue, which tends to block the space in the canal on the apical point of the root and constitutes an ideal filling substance.

The most favorable condition to repair occurs when, some time after treatment, the rest of the canal, generally the part most accessible to instrumentation, remains permanently filled with the claimed composition. The purpose of the surgical opening of root canals is the elimination from the radicular pulp or pulp remains of foreign substances that may penetrate the canal, or the disorganized and infected dentin on the canal walls. 2008/002346

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To provide radiopacity to the preparation, so that it was possible to detect it through an x-ray, we added zinc oxide or iodoform.

Pulpal tissue affections may be acute or chronic, and their etiology may be of infectious, traumatic or medicamentous origin. Histology and bacteriology of severe and chronic pulpitis is described as follows: Bacteriology of severe pulpitis is: streptococcus pyogenes, golden and white staphylococci, diplococci and Gram negative.

Histologically, there is an inflammatory condition with blood vessels hyperemia, exudations, as well as numerous leukocytes and polymorphonuclears. Acute pulpitis may evolve into an acute alveolar abscess or its resolution.

Bacteriology of chronic pulpitis is: viridans hemolytic and non-hemolytic streptococcus, white staphylococcus and Gram negative bacillus. Histologically, we found granulating tissue with new connective tissue, very vascularized, with a defensive function; there were also polymorphonuclears, lymphocytes, granulating tissue, macrophages and giant cells, which may evolve into its resolution or else continue to granuloma, apical cyst and chronic alveolar abscess.

2- PERIAPICAL INFECTIONS

Disorders of periapical tissues are the final result of odontitis (acute and chronic pulpitis), except for the case of traumatic injuries. First, there appears a protection, then an infectious periodontitis, which may be of traumatic or chemical origin. Traumas include general traumas, traumatic occlusions, and mechanical trauma caused by instruments used in the canal. Chemical factors include intoxication by metals or drugs such as arsenic, formocresol or phenol. 3- PERIODONTAL DISEASES

Their origin is undoubtedly organic. On typical processes, a high basal metabolism (hyperthyroidism, hypophysial secretion disorder) may be found. This pathology, whose progression may range from slight and moderate to severe, is very frequent in pregnant women, diabetic patients, people with neurological disorders and immunosuppressed patients. Pain is not a characteristic feature but, when due to the gingival border collapse dental roots are exposed, some painful symptoms may manifest. Histologically, bone is reabsorbed at a parallel level, the bone marrow turns fibrous and medullar spaces are filled with lax connective tissue with several dilated blood vessels. On advanced stages, there is dental mobility, leading even to tooth loss.

This pathology (periodontic) evolves into periodontic abscess; these should be differentiated from the alveolar abscess, since the first ones are originated on periodontal bags or in roots of multi-rooted teeth. 4- STOMATOLOGY

It is the medical study and treatment of injuries produced on the soft parts of the mouth (gums, cheek, tongue, lips).

- Stomatitis (gums and cheeks): it is an inflammatory process that may be caused by local or general factors, allergies or intoxications.

- Lip diseases, cheilitis, fissures and cracks in the corner of the mouth.

On degenerative and infectious injuries, the antibiotic and antiseptic effect of this composition has also been proved, as well as its trophic capacity on mouth mucosa (herpes, cheilitis, labial cracks). We may conclude, without hasting any theories, that from the dentistry perspective, the healing process of the injuries will also follow the described principles of biological activity.

EXPERIENCES OBTAINED WITH THE COMPOSITION OF THE PRESENT INVENTION

CASE 1 : The patient is a 53-year-old female who came to consultation with movement on tooth #35, distal penetrating caries. This tooth is a prosthesis abutment, and the last tooth on the left inferior sector, which is why it is necessary to preserve it. It was decided to perform endodontics using this composition as filling material.

Following the appropriate technique, we applied the claimed composition and after four months, there was no tooth movement.

CASE 2: Male patient that came to consultation due to penetrating caries on tooth #24 below a filling amalgam with painful symptoms upon contact with cold substances. An endodontic treatment was decided, the canal was filled with the composition of the present invention and after three months the periapical abscess had diminished. B2008/002346

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CASE 3: The patient is a 41 -year-old male with an injury on the fulcrum due to amalgam filtration. We applied the preparation and observed reduction at dental root level.

Nowadays, the process continues its reduction and the patient does not experience any symptoms.

CASE 4: The patient is a 24-year-old female with trauma on anterior tooth with comprehensive periapical process on teeth #2 and #1. Now, we observed tooth #2 without periapical process. The patient is still under treatment.

CONCLUSIONS The claimed composition was used with a paste-like consistency on endodontic, traumatic and stomatologic pathologies.

• On endodontic injuries, even though it was a paste, we observed that the composition acted as an excellent filling material.

• Process progression took less time than other products. • In the case of injuries on soft tissues, the healing process developed in accordance with natural process of cicatrisation.

• Healing times were shorter when compared to other products.

• According to patient's statements, pain decreased almost immediately.

• The composition does not produce an unpleasant smell (unlike well-known current products).

• There were no side effects like allergies or intolerance to the composition.

• The disclosed composition is easy to prepare, and does not require mixing with other products for handling. This avoids contamination.

• Surprisingly enough, in practice, it has been proved that just with our composition, favorable results were obtained on different dental pathologies like those described above. No other specific products were required, as it is the case in current treatments. B2008/002346

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USE IN VETERINARY MEDICINE

There is a wide offer of pharmaceutical preparations for veterinary use that are supposed to be useful on bums and open wounds, with simple or multiple actions and additional anti-inflammatory, analgesic, antimycotic, antiseptic, antibacterial and wound-healing effects. To justify their use, or the high cost of many of them, it is said that they accelerate all or some of the wound-healing process. However, on several offered products, we have not learned of any controlled studies that guarantee said actions.

From the point of view of wounds classification and treatment, actions in veterinary medicine are similar to those for human medicine, with strong emphasis on injury cleaning, debridement and detachment of cell detritus and sphacellus.

We may conclude that, as it happens in human medicine, simple injuries are prone to heal by themselves. The therapeutic action of a "wound-healing product" is actually tested on complex injuries. Targeting the assessment of the healing, antibiotic and dermal-epidermal regenerative activity of the claimed composition, we have treated inflammatory, traumatic and surgical injuries on small animals, and every case resulted in complete tissue healing.

Apart from the referred examples, we consider that the disclosed composition can be used on large animals as well, on injuries that, according to professional criteria, need wound-healing, antibiotic and antiparasitic activity.

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Claims

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1) A pharmaceutical composition for selective stimulation of wound healing processes, dermal-epidermal normal tissular trophism processes for internal and external use, comprising 0.08 to 0.12% by weight of gentamicin sulphate, 0.8 to 1.2% by weight of metronidazole, 0.4 to 0.8% by weight of papain, 6 to 14% by weight of balsam of Peru, the remaining being an excipient or vehicle pharmaceutically acceptable.

2) Composition according to claim 1 , comprising 0.1 g Gentamicin sulphate, 1 g Metronidazole, 0.6 g Papain, 10 g Balsam of Peru, 44,15 g lanoline and 44,15 g Vaseline.

3) Composition according to claim 1 , comprising zinc oxide or iodoform to provide radiopacity to the composition.

4) Process to prepare the composition according to claim 2, comprising the following steps: - Place the basic excipient in a mortar, this composition is made of equal parts of anhydrous lanolin or acetylated or ethoxylated lanolin to replace anhydrous lanolin and solid vaseline, blend it properly until complete homogenization,

- In another mortar, pulverize metronidazole until reduce it to fine powder and put it into 10 ml of propylene glycol,

- Add the excipient in small quantities, blending all together properly,

- Dissolve Gentamicin Sulphate in 2 ml of boiled and cooled distilled water and then add to the previous preparation and blend it until complete homogenization, - Dissolve Papain in 4ml of boiled and cooled distilled water and then add to the previous preparation and blend it,

- Add the Balsam of Peru very slowly to the previous preparation and blend it until complete homogenization.

5) A pharmaceutical composition according to claim 1 , wherein it can be prepared as creams, embedded gauze, spray, ovules, and vaginal creams.

6) Use of the composition according to claims 1 to 5, to prepare a medicine for the treatment of selective stimulation of wound healing processes, dermal-

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epidermal normal tissular trophism processes for internal and external use, in human, veterinary and odontologic medical treatments.

7) Use of the medicine prepared according to claim 6, for medical or veterinary treatment of ulcers due to pressure (eschars), varicose ulcers, trophic ulcers due to vascular insufficiency, diabetic ulcers, 1 and 2 degree bums, thermal and radiotherapy burns, healing of all kinds of severe and chronic wounds, simple or complex, healing of post-surgical wounds (granulation stimulant for future grafts), excoriations, dermic abrassion of chemical or physical origin, diabetic feet injuries (ulcers, exposed tissue bed caused by amputations, sequels to amputations, sequels to infections due to drained abscesses or phlegmons, secreting or sphacelus wounds), foul-smelling lesions (tissular necrosis, fungating tumors, gravitational ulcers), infectious dermatosis (piodermitis, erisipela, acne, impetigo, diaper rash), inflammatory dermatosis (psoriasis, eczemas, dehydrosis, non-specific simple or complex dermatitis, erythema pernio, ectoparasitosis (scabies), superficial mycosis (susceptible to the composition).

8) Use of the medicine according to claim 6, to apply in odonthology, in endodontic treatments, traumatic and infectious pulpitis, severe or chronic, abscesses, stomatology (cheilitis, fissures, infectious herpes), dental mobility and surgery (alveolitis, retained tooth).