ES2672314A2 - Oily active pharmaceutical ingredient (api) for the treatment of skin conditions, compositions comprising same, and use thereof for preparing said compositions - Google Patents

Abstract

Oily active pharmaceutical ingredient (API) for the treatment of skin conditions comprising: oleic acid from approximately 35 to approximately 55 g, palmitic acid from approximately 15 to approximately 32 g, linoleic acid from approximately 10 to approximately 20 g, stearic acid from approximately 7.5 to approximately 9 g, linolenic acid from approximately 0.5 to approximately 1.5 g, vitamin A (as palmitate) 1.7 MIU/g from approximately 0.8 to approximately 1.2 g, and vitamin E (as acetate) from approximately 0.1 to approximately 0.24 g. Composition of epidermis regenerative cream, composition of epidermis cicatrizant cream, composition of epithelial nourishing cream, composition of a cicatrizant gel in aerosol, nasal liquid composition for treating allergic rhinitis, cream composition for treating psoriasis and composition of liquid soap comprising same. Use of same for preparing the compositions.

Description

DESCRIPTION

Oily active pharmaceutical ingredient (IFA) for the treatment of skin conditions, compositions comprising it and its use to prepare them

 5

Field of invention

This invention belongs to the field of pharmaceutical compositions for the treatment of the dermis, in particular those compositions related to tissue regeneration, more particularly with pharmaceutical compositions for epithelial regeneration. 10

Description of the Prior Art

Despite the growth and advances in medical technology, the loss of tissues or organs as a result of aging processes, degenerative or infectious diseases, and accidents and burns, remains a serious health problem worldwide.

It is estimated that approximately 1% of the world's population may suffer from a serious burn at some time in their life. In Europe, annually, about 20 million people receive medical care for burns. In the United States, the incidence of burned people is 1.5 million a year, of which 60,000-80,000 require hospitalization, and between 5,000-6,500 die from their injuries. In South America, epidemiological investigations reveal that the most common causes correspond to domestic, industrial or labor incidents, and the most frequent agents are hot liquids, followed by direct flame and electricity.

The burns produce a disruption of the vital function of the organ of greater extension of the body that is the skin. The mechanism that causes the burn causes protein denaturation and physical disruption of cellular structures. Direct intravascular destruction of endothelial cells and erythrocytes with thrombosis occurs due to their accumulation.

The function of the skin is protective, as a barrier to infections and water evaporation helping to maintain the balance of fluids and electrolytes. Burned skin 35 decreases its effectiveness in regulating body temperature by heat loss

through evaporation and irregularity of motor regulation. Evaporation losses occur through the burn.

The skin covers the entire body and has a surface area of between 1.2 and 2.2 m2, weighing about 4 to 5 kg which corresponds to 7% of the total weight of an adult. The skin is also known as tegument, which means coverage, but its function goes beyond being the envelope of the body, it is also flexible but resistant and supports the constant punishment of external agents.

The skin can vary in thickness between 1.5 and 4.0 mm depending on the area of the body and 10 is composed of two different regions: epidermis and dermis.

The epidermis is the outermost protective shield of the body formed by epithelial cells, it is not vascularized and nutrients reach it from the blood vessels of the dermis by diffusion. fifteen

Underlying the epidermis is the dermis, which forms the largest volume of the skin and is a strong choreoidal layer of connective tissue, which is provided with blood vessels.

Under the dermis there is a third layer that shares some protective functions 20 with the skin but that strictly speaking is not part of it, this layer is called hypodermis or subcutaneous fascia and is basically made up of adipose tissue, a type of connective tissue, with a certain amount of areolar connective tissue.

The hypodermis, in addition to storing fat, serves as anchorage of the skin to the underlying tissues, mainly muscles, sufficiently loose so that the skin can slide with relative freedom over those structures.

The epidermis is structurally formed of stratified squamous epithelium and keratinized with four different cell types and four or five different layers. 30

The cells that populate the epidermis are: keratinocytes, whose main role is the production of keratin, a fibrous protein that gives the epidermis its protective function; melanocytes, spider-shaped cells that are in the deepest layer of the epidermis and their function is to secrete the melanin pigment; Merkel cells, occasionally present at the border between the epidermis and the dermis; and Langerhans cells (or epidermal cells

dendritic) that reach the epidermis from the bone marrow, being macrophages that help activate the immune system.

According to the region of the body, the epidermis can be thin or thick depending on the friction or the load to which the skin is subjected. 5

In thick areas (palms, fingertips and soles of the feet) the epidermis has five layers or strata, which from deep to superficial are: basal stratum, firmly anchored to the underlying dermis by means of a wavy border where between 10 and 25% of the cells in this layer are melanocytes and sometimes Merkel cells can be seen; spiny stratum, of a thickness of several layers of cells that have a filament system forming as a tissue; granular, fine stratum with 3 to 5 layers of thick cells, and there is a pronounced change in the appearance of keratinocytes; lucid stratum only present in the thick epidermis is a thin and translucent band above the granular stratum consisting of a few rows of dead keratinocytes with their indifferentiated or blurred borders; and more external stratum corneum, an area between 20 and 30 layers thick of cells that constitutes up to three quarters of the thickness of the epidermis of dead cells of thick plasma membrane and very keratinized that constitute a protective shell of maximum wear resistance and penetration twenty

The dermis is made of strong and flexible connective tissue that holds the body together, as a containment sheath, presenting a strong influx of nerve fibers with sensory receptors, blood vessels and lymphatic vessels. Most of the hair follicles and the sweat and sebaceous glands, which pour their contents outside 25 into the epidermis, are in the dermis.

The dermis has two layers: papillary, thin and superficial layer of areolar connective tissue in which the collagen and elastin fibers form a loose woven mat that is heavily invaded by blood vessels; and reticular, irregular dense connective tissue that constitutes 30 80% of the thickness of the dermis.

The skin color is defined by three colored substances or pigments: melanin, the only pigment manufactured in the skin, yellow to reddish brown to black; carotene, orange pigment that has a tendency to accumulate in the stratum corneum as well as in the fatty tissue of the hypodermis; and hemoglobin, red pigment of the red blood cells of the

blood and gives a pinkish color to the skin of light skinned people by circulating through the capillaries of the dermis.

The skin protects the human body from any type of external attack such as blows, burns, pressure, loss of water and heat, actions of chemical agents, penetration of germs.

The skin is 70% water and is what allows vitality in it.

The skin cells found in the epidermis - upper layer of skin - reproduce every 28 days, so the cuts or any type of wound can heal.

The secretion glands can be eccrine -secre liquid and sweat-, apocrine and holocrine or sebaceous.

 fifteen

The skin regulates body temperature by eliminating heat, evaporating secreted sweat and in turn eliminating all those substances that are harmful.

Regardless of the type of wound in question and the extent of tissue loss, any healing process takes place in phases that overlap in time and cannot be separated from each other. As a general rule, healing is mainly divided into three phases, namely:

The inflammatory / exudative phase that begins at the time the wound occurs and its duration is approximately three days depending on the physiological conditions. The first 25 vascular and cellular reactions consist of coagulation and hemostasis, and conclude after approximately 10 minutes have elapsed. The coagulation system is activated through a complex thrombocyte agglomeration process, thereby permanently closing the site of the lesion. Inflammation represents the complex defense reaction of the organism against the action of different harmful agents of mechanical, physical, chemical or bacterial origin. Inflammation is characterized by four symptoms: rubescence (blushing), heat, swelling (tumor) and pain.

The proliferative or proliferation phase is the second phase of wound healing where cell proliferation predominates in order to achieve vascular reconstitution and return

to fill the defective area by granular tissue, whose formation is predominantly initiated by fibroblasts. This phase begins approximately from the fourth day since the injury occurred.

The differentiation and reconstitution phase occurs approximately between the 6th and 10th day 5 where the maturation of the collagen fibers begins. The wound contracts, the presence of vascular and water in the granular tissue is reduced more and more, which gains in consistency and eventually transforms into the scar tissue. This process includes the reconstitution of epidermal cells through mitosis and cell migration, mainly from the edges of the wound. The epithelialization of the wound closes the healing cycle, which is closely related to the formation of the granulation of the wound.

According to the WHO, more than one million burns occur in the United States each year. Approximately 5,000 of these injuries are fatal, so burns 15 occupy the fourth cause of death due to unintentional injuries.

The risk of burn injury is even greater in developing countries, where living conditions are poor and access to care is limited.

 twenty

According to the WHO, 90% of burns occur in developing countries or underdeveloped nations and 70% of them occur in children. Most burns can be prevented, as evidenced by the decrease in burn incidence rates in the United States, which are largely attributed to prevention strategies. 25

However, burns are constantly mentioned as one of the first ten causes of death in children under 5 years and adults over 34 years.

The decrease in mortality in patients affected by burns in the last 30 years has been achieved through aggressive resuscitation, early excision and wound coverage, rational use of antibiotics, nutritional support and the development of burn centers specialized in the attention of this type of patient.

The causative agents of burns are extremely varied and are grouped into three main categories: thermal burns, chemical burns and electric burns.

Thermal burns are classified as: contact burns with a hot solid 5 or with a hot liquid; flame burns, of variable extension but almost always deep; and burns by ultraviolet radiation after sun exposure and also by ionizing radiation.

Chemical burns can be classified as: acid burns, they are limited and 10 medium deep if washed abundantly; and burns by bases or alkalis, deeper than those produced by acids and generally evolutionary since it takes time to evaluate its extension.

Electric burns can be of two types: electric flash burns, when there is no current flow through the body, they are quite superficial lesions and affect exposed body surfaces; and electrical burns with the passage of current through the organism, are almost always very deep lesions, in which the percentage of burned body surface is not indicative of the real existing damage, given that in severe cases there are internal injuries. twenty

The percentage of burned body surface is not only a determining factor of the prognosis of the burned patient, but also becomes an important value for the estimation of fluid requirements, in the acute phase of severe burns. Therefore, it is important to make a careful and accurate estimate of the percentage of body surface affected by the burn.

In addition to the extension, a thorough evaluation of the depth of the burns is important, which is of great value not only to determine the vital prognosis, but also the functional one after the burn. In this way, you can recognize: 30

a) First degree or superficial burns, which are the mildest and are almost always due to sun exposure. They manifest in the form of erythema and are almost always painful.

b) Burns of second degree superficial type, affect up to the papillary dermis and are characterized by the existence of blisters due to exudate produced after vascular injury. Like superficial burns they are usually painful.

c) Burns second degree deep type, where the burn affects the reticular dermis 5, the appearance of the skin is red-pale, and they are painless due to the total affectation and destruction of the nerve endings.

d) Third degree burns affect the entire thickness of the skin, and the skin color is variable, with a cardboard-like consistency, inelastic. Due to the destruction of the nerve endings, these types of burns are anesthetic.

e) Fourth degree burns affect all skin structures and also deep structures such as muscle, bones, etc.

 fifteen

There are many factors that influence the prognosis of the burn patient. Among them are: patient age, extent of the burn, depth of the lesion, etiology, involvement of the respiratory tract, intercurrent diseases and location of the burn.

 twenty

Until today several types of topical specific treatments to regenerate dermis are known.

The application of a silver sulfadiazine cream on a wound to ensure healing, being one of the most frequent topics used as a prophylactic agent. The first treatment given to second degree burns is silver sulfadiazine as the primary component. It is a white, insoluble and commercially available 1% ointment in preparation of base cream with a surface anesthetic, without smell, to be applied once or twice a day.

 30

Its main function is antimicrobial, it is of low toxicity that increases with the treated surface and can cause some pain in the application.

The mechanism of action of silver sulfadiazine would be to hinder DNA duplication, however this process is not well known, and it is an inhibitor of p-35 aminobenzoic acid, which is an important bacterial metabolite.

In extensive burns a lethal hyperosmolarity has been observed by absorption of the glycol component of the silver-based sulfadiazine cream.

With its use a gray-yellow color is sometimes formed on the surface of the 5 treated burns, known as pseudo bedsores. The dark color produced by silver salts in contact with air and tissue fluids masks the wash and makes diagnosis difficult.

It does not contain a high concentration of lidocaine, that is, it does not have great anesthetic power. 10

Today there is no other product on the market that provides the necessary conditions in a wound to regenerate dermis than silver sulfadiazine that has been in use for more than 50 years.

 fifteen

However, with its use it usually takes 15 to 20 days to form a dermis, so the nerve endings are discovered for this period of time and therefore the patient continues with pain.

The cures are difficult since it forms a black color film, which, if not removed correctly, is fixed in a very tight way to the surface of the skin, so that sometimes it is necessary to remove it with a scalpel.

Although its concentration is low in blood, there are described side effects such as methemoglobinemia, hyperosmolarity, skin irritation and severe skin allergies, 25 among the most prominent.

There are also other treatments through the use of different types of dressings, namely:

-Hydrocolloidal dressings containing various constituents such as gelatin, pectin and sodium carboxymethyl cellulose in an adhesive polymer matrix. These dressings form a gel when its inner layer comes into contact with the exudate, which in turn facilitates the autolytic debridement of the lesion. Examples of these hydrocolloidal dressings are Comfeel (Coloplast) and DuoDerm (ConvaTec).

 35

-Polyurethane film dressings that are transparent sheets covered with adhesives that are applied directly to the lesion. They are permeable to water vapor, oxygen and carbon dioxide, but not to water or bacteria. Depending on the magnitude of the exudation, the dressings can be kept on the lesion for several days. Sheet dressings are appropriate for lesions with light exudates. Two examples 5 of polyurethane sheets are OpSite (Smith & Nephew) or Tegaderm (3M Company).

-The hydrogel dressings are gels with high water content that contain insoluble polymers. Its constituents are modified carboxymethyl cellulose, hemicellulose, agar, glycerol and pectin. They have the ability to absorb liquids and, therefore, can incorporate part of the exudate from the lesion. Its property of providing liquid can also help the debridement of the lesion and the maintenance of a humid environment. Hydrogels are available in amorphous form of loose gel and in the form of sheets where the gel is presented with a fixed three-dimensional macrostructure. Amorphous hydrogels include products such as IntraSite (Smith & Nephew) and Solugel, while sheet 15 hydrogels comprise Aquaclear and Nu-gel (Johnson & Johnson).

-Nylon dressings with silicone cover consist of a flexible polyamide net coated with non-biological compounds containing silicone. They act as a layer in direct contact with the lesion and its mesh structure allows the exudate to drain from the burned surface. They function primarily as a non-adhesive dressing and, therefore, reduce potential damage during dressing changes. An example of these dressings includes Mepitel (Mölnlycke).

-Biosynthetic skin substitutes are a group of materials that have been developed to mimic skin function by replacing the epidermis or dermis, or both. In general terms, manufactured epidermal substitutes allow the reepithelialization and exchange of gases and liquids, which in turn provides protection against the installation of bacteria and mechanical coverage. Examples of these dressings include Biobrane (Dow Hickam / Bertek Pharmaceuticals) and TransCyte (Advanced Tissue Sciences). 30

-Antimicrobial dressings containing silver and iodine are used to treat the biological burden of the lesion by reducing the risk of invasive infection by decreasing bacterial colonization. Specialized products containing antimicrobials include Acticoat (which supplies nano-crystalline silver) and Iodosorb (iodocadexomer). There are currently 35

manufactured several products containing silver, such as: Contreet (hydrocolloidal with silver), Advance (foam with silver) and Aquacel Ag (fiber dressing with silver, ConvaTec).

-Fiber dressings such as calcium alginate dressings are absorbent, biodegradable and derived from seaweed. Alginate dressings can help maintain a moist microenvironment that promotes healing, while limiting the secretions of the lesion and reducing bacterial contamination. They are useful in lesions with moderate to intense exudate. The alginate can be removed with saline irrigation, which reduces interference with the healing process and can relieve the pain experienced by patients. Some examples of alginate dressings 10 are: Algosteril (Johnson & Johnson), Comfeel Alginate Dressing (Coloplast), Carrasorb H (Carrington Laboratories), Kaltostat (ConvaTec).

-The pads for covering lesions include simple non-adhesive dressings, woven viscose dressings (for example N / A Dressing - Johnson & Johnson), tulle dressings and 15 gauze. They are usually presented as woven cotton pads that are applied directly to the surface of the wound. They may not contain drugs (for example paraffin gauze dressing) or contain them (for example with povidone iodine or chlorhexidine).

Despite the increase in alternatives of the types of dressings available, traditional paraffin-impregnated gauze dressings and absorbent cotton or gauze are still frequently used. Paraffin and gauze dressings are relatively inexpensive. In many parts of the world where resources to treat burns are limited, even simple medical dressings may not be available. In these circumstances, the lesions can be treated with various materials, such as banana leaves or potato peel. In addition, open treatment of burn injuries is also frequently practiced.

It should be taken into account that dressings are not practical in folds, interdigits and irregular lesions of large extensions. 30

On the other hand, all natural products that are extracted from leaves of plants, for example aloe vera, palm leaf, etc., have the property of moisturizing the affected area until it granulates and / or heals, without being able to measure dose, time , pain, etc.

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Therefore, it is necessary to have a cure that allows wound healing, generating the dermis in a short period of time, thus reducing the time during which the patient suffers pain. The product to be used must not form, in a secondary way, scabs or bedsores that are difficult to remove. It should be possible to avoid a higher content of lidocaine or other local anesthetic to remove pain to the patient, this being one of the main nuisances that normally used treatments have. It must be a natural, totally ecological product that has an accelerating action on cell generation and epithelium, thus avoiding side effects in both blood and healthy skin (not irritability). It must have vasolidating properties to facilitate oxygenation of the area accelerating cell proliferation. It should preferably be accessible to the entire population of any social class. It should not be of complex application, nor should it have limitations in its application according to the affected area. Preferably, the product should have a wide therapeutic use intended to treat second and third degree burns, ulcers of both venous and arterial limbs, psoriasis, scoriations, diaper rash of the infant, an aesthetic application (anti-wrinkle and skin elasticizer). fifteen

The product must not have major contraindications, it must have a high dermal tolerance without irritation and lack systemic effects.

So far there is no known product for epithelial regeneration that meets all these conditions.

Summary of the Invention

The object of the present invention is then an oily active pharmaceutical ingredient (IFA) for the treatment of skin conditions, comprising:

Oleic acid from about 35 to about 55 g,

Palmitic acid from about 15 to about 32 g,

Linoleic acid from about 10 to about 20 g, 30

Stearic acid from about 7.5 to about 9 g,

Linolenic acid from about 0.5 to about 1.5 g,

Vitamin A (as palmitate) 1.7 MUI / g from about 0.8 to about 1.2 g, and

Vitamin E (as acetate) from about 0.1 to about 0.24 g. 35

Preferably, the active pharmaceutical ingredient (IFA) comprises:

Oleic acid approximately 48.73 g,

Palmitic acid approximately 26.0 g,

Linoleic acid approximately 14.9 g, 5

Stearic acid about 8.1 g,

Linolenic acid approximately 1.1 g,

Vitamin A (as palmitate) 1.7 MUI / g approximately 1.0 g, and

Vitamin E (as acetate) approximately 0.17 g.

 10

It is another object of the present invention, an epidermis regenerating cream composition comprising from about 54 g to about 66 g of the active pharmaceutical ingredient (IFA), from about 0.9 to about 1.1 g of L-arginine, and of about 1.8 to about 2.2 g of girofle (clove essential oil), together with pharmaceutically acceptable excipients, carriers and solvents.

Preferably, the pharmaceutically acceptable excipients, carriers and solvents of the epidermis regenerating cream composition are 30 mol ketostearyl alcohol, ketostearyl alcohol, essence, 20 mol sorbitan monolaurate, methylparaben, 20 propylparaben, and distilled water csp 100 g.

Also preferably, the use of the active pharmaceutical ingredient (IFA) is to prepare a pharmaceutical composition for application in the regeneration of epithelial tissues, vasodilator and local anesthetic. 25

More preferably, the application is in second and third degree burns, ulcers in both venous and arterial lower limbs, bedsores, vasculitic ulcers, and post operative scars.

 30

It is yet another object of the present invention, an epidermal healing cream composition comprising from about 45 g to about 55 g of the active pharmaceutical ingredient (IFA), from about 6.3 g to about 7.7 g of zinc oxide, and of about 1.8 g to about 2.2 g of boric acid, together with pharmaceutically acceptable excipients, carriers and solvents. 35

Preferably, the pharmaceutically acceptable excipients, carriers and solvents of the epidermal healing cream composition are 30 mol ketostearyl alcohol, ketostearyl alcohol, essence, 20 mol sorbitan monolaurate, methylparaben, propylparaben, and distilled water csp 100 g.

 5

Also preferably, the use of the active pharmaceutical ingredient (IFA) is to prepare a pharmaceutical composition for epidermis healing application.

More preferably, the application in epidermis healing is in first degree burns, scoriations, paspas, and lesions in the epidermis of any etiology. 10

It is yet another object of the present invention, an epithelial nourishing cream composition comprising from about 45 g to about 55 g of the active pharmaceutical ingredient (IFA), together with pharmaceutically acceptable excipients, carriers and solvents. fifteen

Preferably, the pharmaceutically acceptable excipients, carriers and solvents of the epithelial nourishing cream composition are 30 mol ketostearyl alcohol, ketostearyl alcohol, essence, 20 mol sorbitan monolaurate, methylparaben, propylparaben, and distilled water csp 100 g. twenty

Also preferably, the use of the active pharmaceutical ingredient (IFA) is to prepare an epithelial nourishing cream composition for application in nutrition, elasticization and skin texturing.

 25

More preferably, the application is in glass skin (epidermolysis bullosa).

It is also another object of the present invention, an aerosol healing gel composition comprising from about 27 g to about 33 g of the active pharmaceutical ingredient (IFA), and from about 1.8 g to about 2.2 g of girofle 30 (oil clove essential), together with pharmaceutically acceptable excipients, carriers and solvents.

Preferably, the pharmaceutically acceptable excipients, carriers and solvents of the aerosol healing gel composition are a mixture of isobutane, butane and propane with minor components of other aliphatic saturated hydrocarbons such as

propellant and the following substances: 30 mol ketostearyl alcohol, ketostearyl alcohol, essence, cyclomethicone, mentyl lactate, 20 mol sorbitan monolaurate, methylparaben, propylparaben, and distilled water csp 100 g.

Also preferably, the use of the active pharmaceutical ingredient (IFA) is to prepare a pharmaceutical composition for application in first and second degree burns.

More preferably, the application is as a local anesthetic for first and second degree burns, bacteriostatic disinfectant, decreased cell injury and tissue regeneration. 10

It is still yet another object of the present invention, a nasal liquid composition comprising from about 2.7 g to about 3.3 g of the active pharmaceutical ingredient (IFA), and from about 0.27 g to about 0.33 g of lactate. mentyl, together with pharmaceutically acceptable excipients, carriers and solvents.

Preferably, the pharmaceutically acceptable excipients, carriers and solvents of the nasal liquid composition are sorbitan 20 mol monolaurate, 30 mol ketostearyl alcohol, ketostearyl alcohol, carboxymethyl cellulose microcrystalline cellulose, xylitol, 20 polysorbate 80, and 100 ml demineralized water.

Also preferably, the use of the active pharmaceutical ingredient (IFA) is to prepare a pharmaceutical composition for application as a nasal mucosa regenerator.

 25

More preferably, the application is in chronic rhinitis and lesions of the nasal mucosa due to different etiologies.

It is also another object of the present invention, a cream composition for treating psoriasis comprising from about 45 g to about 55 g of the active pharmaceutical ingredient (IFA), and from about 0.9 g to about 1.1 g of papain 30,000 U / mg, together with pharmaceutically acceptable excipients, carriers and solvents.

Preferably, the pharmaceutically acceptable excipients, carriers and solvents of the cream composition for treating psoriasis are 30 mol ketostearyl alcohol, alcohol

ketostearyl, sorbitan monolaurate 20 moles, essence, citrus pectin, propylene glycol, triethanolamine, methylparaben, propylparaben, and distilled water csp 100 g.

Also preferably, the use of the active pharmaceutical ingredient (IFA) is to prepare a pharmaceutical composition for application as a limitation and inhibitor of dermatitis and psoriasis scaling.

More preferably, the application is in psoriasis and psoriasiform lesions.

It is another additional object of the present invention, a liquid soap composition comprising from about 18 g to about 22 g of the active pharmaceutical ingredient (IFA), from about 0.09 g to about 0.11 g of girofle (clove essential oil odor), and about 1.8 g to about 2.2 g of superoxide dismutase, together with pharmaceutically acceptable excipients, carriers and solvents. fifteen

Preferably, the pharmaceutically acceptable excipients, carriers and solvents of the liquid soap composition are sodium lauryl ether sulfate, citric pectin, triethanolamine, propylene glycol, coconut betaine, ketostearyl alcohol 30 moles, ketostearyl alcohol, sorbitan monolaurate 20 moles, methylparaben, propylparaben, essence, 20 and distilled water csp 100 ml.

Also preferably, the use of the active pharmaceutical ingredient (IFA) is to prepare a pharmaceutical composition for application as a liquid soap inhibitor of fatty acid reduction, a characteristic phenomenon in advanced ages of the human being. 25

More preferably, the application is in daily hygiene of the elderly to inhibit the characteristic smell of the elderly.

Brief Summary of Figures 30

Figures 1a and 1b correspond to representative photographs of Application Example 1.

Figures 2a and 2b correspond to representative photographs of Application Example 2.

 35

Figures 3a and 3b correspond to representative photographs of Application Example 3.

Figures 4a and 4b correspond to representative photographs of Application Example 4.

Figures 5a, 5b and 5c correspond to representative photographs of Application Example 5. 5

Figures 6a, 6b and 6c correspond to representative photographs of Application Example 6.

Figures 7a, 7b and 7c correspond to representative photographs of Example of Application 7.

Figures 8a and 8b correspond to representative photographs of Application Example 8.

Figures 9a and 9b correspond to representative photographs of Application Example 9. 15

Figures 10a, 10b and 10c correspond to representative photographs of Application Example 10.

Figures 11a and 11b correspond to representative photographs of Application Example 20 11.

Figures 12a and 12b correspond to representative photographs of Application Example 12.

 25

Figures 13a and 13b correspond to representative photographs of Application Example 13.

Detailed description of the invention

 30

The object of the present invention is an active pharmaceutical ingredient (IFA) vehiculized in the form of cream, aerosol cream, nasal liquid composition, liquid soap composition against noneal odor, composition in antipsoriatic cream for maintenance and regeneration of the dermis In various circumstances, it also acts as a local anesthetic and has a high tissue regeneration power and is a vasodilator. 35

Among its main applications are: second and third degree burns, ulcers in the lower, venous or arterial limbs, bedsores, vasculitic ulcers, post-operative scars, noneal odor control, wrinkle treatment, stretch marks and skin deterioration in general .

 5

The IFA generates a moist healing through a treatment that involves 1 to 3 daily cures so that in less than five days new dermis is generated, which other creams take 15 to 20 days.

The object of the present invention is therefore an active pharmaceutical ingredient (IFA) 10 which comprises a synergistic mixture of fatty acids and fat soluble vitamins, namely:

Oleic acid from about 35 to about 55 g,

Palmitic acid from about 15 to about 32 g,

Linoleic acid from about 10 to about 20 g, 15

Stearic acid from about 7.5 to about 9 g,

Linolenic acid from about 0.5 to about 1.5 g,

Vitamin A (as palmitate) 1.7 MUI / g from about 0.8 to about 1.2 g, and

Vitamin E (as acetate) from about 0.1 to about 0.24 g. twenty

In a preferred form, the IFA object of the present invention comprises:

 Composition component (IFA)

 Quantities

 Oleic acid

 48.73 g

 Palmitic acid

 26.00 g

 Linoleic acid

 14.90 g

 Stearic acid

 8.10 g

 Linolenic acid

 1.10 g

 Vitamin A (as palmitate) 1.7 MUI / g

 1.00 g

 Vitamin E (acetate)

 0.17 g

Variations of ± 10% in these quantities are admissible and are mainly due to the origin of the raw materials used and to normal variations typical of the measurements.

Oleic acid is a monounsaturated fatty acid of the omega 9 series typical of vegetable oils such as olive oil and avocado oil.

Its empirical chemical formula is C18H34O2 and the developed CH3 (CH2) 7CH = CH (CH2) 7COOH.

Its name IUPAC is cis-9-octadecenoic acid, and its lipid shorthand name is 10 18: 1Δ9. The saturated form of this acid is stearic acid.

Olive oil comprises 55-80% oleic acid and grape seed oil 15-20%.

 fifteen

At the topical level it has no systemic effects. It exerts a beneficial action on blood vessels reducing the risk of cardiovascular disease.

Palmitic acid or hexadecanoic acid, is a saturated long chain fatty acid formed by sixteen carbon atoms. It is a white solid that melts at about 63 ° C. Its chemical formula developed is CH3 (CH2) 14COOH.

Palmitic acid is the main saturated fatty acid in the diet, constituting approximately 60% of them. It is the most abundant in meat and dairy fats, and in vegetable oils such as coconut oil and palm oil. 25

It is the least healthy fatty acid because it is the one that most increases blood cholesterol levels, so it is the most atherogenic.

It is the second fatty acid that is produced during lipogenesis and from it other longer chain fatty acids or with double bonds can be formed.

Linoleic acid is an essential fatty acid, that is, the body cannot synthesize it and has to be acquired through intake. It is a polyunsaturated fatty acid, with two double bonds whose formula developed is CH3 (CH2) 4CH = CHCH2CH = CH (CH2) 7COOH and 35

It has an 18: 2Δ9,12 configuration. It is the precursor of numerous derivatives that are formed in elongation, saturation reactions or both.

Increases defenses, lowers body fat levels, lowers blood pressure, helps control cholesterol and triglycerides, reduces the risk of diseases of the circulatory system, decreases platelet aggregation, helps eliminate harmful fats for the body, It intervenes in a proper functioning of the nervous and visual systems.

The linoleic acid is known as omega 6 fatty acid since the first double bond to be counted from the omega carbon, that is, the one carrying the methyl group (-CH3) cis, is in position 6.

It is found in various vegetable oils, such as sunflower and soy, in eggs and poultry. fifteen

Stearic acid is a saturated fatty acid of 18 carbon atoms present in animal and vegetable oils and fats.

At room temperature it is a wax-like solid. Its chemical formula is CH3 (CH2) 16COOH and its name IUPAC is octadecanoic acid. It has a hydrophobic chain of carbon and hydrogen.

It is obtained by treating animal fat with water at a high pressure and temperature, and by hydrogenating vegetable oils. Some of its salts, mainly sodium and 25 potassium, have surfactant properties. It is widely used in the manufacture of candles, soaps and cosmetics. Together with other products it is used for the development of creams for dry skin.

Linolenic acid is an omega-3 polyunsaturated fatty acid for the α isomer, whose acronym for English is ALA. It consists of an 18 carbon chain with 3 double bonds at positions 9, 12 and 15. Given the large number of unsaturations, it is an unsaturated fatty acid that oxidizes easily. Antioxidants such as vitamin E and polyphenols are added to oils rich in this fatty acid.

 35

Its structural chemical formula is CH3-CH2-CH = CH-CH2-CH = CH-CH2-CH = CH- (CH2) 7-COOH, and its molecular formula is C18H30O2.

Α-Linolenic acid (ALA) is found in abundance in chia seeds. It is an essential polyunsaturated fatty acid, since it is not synthesized by humans. It is a 5 component of many common vegetable oils and is important for human nutrition.

Structurally ALA is 9,12,15-octadecatrienoic acid with all double cis bonds, whose biochemical name is 18: 3Δ9,12,15. 10

ALA is a carboxylic fatty acid isomer of gamma-linolenic acid, an omega-6 fatty acid.

Linoleic acid together with other omega-6 fatty acids competes with the omega-3 series fatty acids to form part of cell membranes, also influencing human health.

Vitamin A is a fat-soluble vitamin that has several important functions in the body such as resistance to infections, antibody production, bone growth, fertility. But its main function is what it fulfills in the retina. Retinol is transported to the retina, where it is oxidized to 11 cis-retinal which is carried to the cells present in the retina, in this case to the rods where it joins a retinal protein called opsin to form the visual pigment called rhodopsin. These rods together with rhodopsin detect very small amounts of light. 25

This vitamin is also very necessary for the growth and differentiation of epithelial tissue, for example that of the eye, respiratory and gastrointestinal tract, in reproduction and embryonic development.

 30

Vitamin A is usually expressed in International Units (IU) or as retinol equivalents (ER), which correspond to 1 µg of retinol, 6 of β-carotenes or 12 µg of other carotenes.

Vitamin A acts by stimulating mitosis in the basal layer of the skin, helps restore damaged tissues, increases cell turnover and favors the maintenance of the structure of the epidermis, intervening in the control of cell proliferation.

In connective tissue, vitamin A increases the synthesis of collagen. It has a regulatory effect on keratin formation. Vitamin A helps with rapid wound healing and overall skin protection.

Vitamin E is also a fat-soluble vitamin required for a normal pregnancy. Vitamin E is found in many foods, mainly of plant origin, especially 10 in those with green leaves such as broccoli and spinach, seeds, including soybeans, wheat germ and brewer's yeast. It can also be found in animal foods such as egg yolk.

Normally a contribution of this vitamin to vegetable oils is usually considered. 15 Some diets that use cereal breakfasts provide a large amount of vitamin E to the body.

Vitamin E is a family of polyrenoid compounds. Vitamin E in its natural state has eight different forms of isomers, four tocopherols and four tocotrienols. All of the eight isomers have an aromatic ring, called chromane, with a hydroxyl group and a polyronoid chain. If the polyrenoid chain is saturated they will correspond to tocopherols and if unsaturated, tocotrienols. There are two forms alpha α, beta β, gamma γ and delta δ for both isomers (tocopherols and tocotrienols), and is determined by the number of methyl groups in the aromatic ring. Each of the forms has its own biological activity. 25

All the actions of tocopherols seem to be determined by their antioxidant agent character, and which, in particular, prevents lipid peroxidation reactions.

It provides advantages in some aspects of the circulatory system, has antioxidant properties and ocular properties, prevents Parkinson's, controls cholesterol levels, helps hair growth and prevents dementia in old age.

The described IFA is useful for formulating an epidermis regenerating cream. In a preferred embodiment of this cream composition, each 100 g contains:

Active Pharmaceutical Ingredient (IFA) from about 54 g to about 66 gL-Arginine from about 0.9 to about 1.1 g of L-arginine Girofle (clove essential oil) from about 1.8 to about 2.2 g

The composition comprises the following pharmaceutically acceptable excipients, carriers and solvents: 30 mol ketostearyl alcohol, ketostearyl alcohol, essence, 20 mol sorbitan monolaurate, methylparaben, propylparaben, and distilled water csp 100 g.

In a preferred form, the composition of the epidermis regenerating cream according to the present invention is as follows:

 Composition Component

 Quantities

 Oleic acid

 29.24 g

 Palmitic acid

 15.60 g

 Linoleic acid

 8.94 g

 Stearic acid

 4.86 g

 Linolenic acid

 0.66 g

 Vitamin A (as palmitate) 1.7 MUI / g

 0.60 g

 Vitamin E (acetate)

 0.10 g

 Ketostearyl Alcohol (30 moles)

 7.00 g

 Ketostearyl alcohol

 6.00 g

 Girofle (clove essential oil)

 2.00 g

 Essence

 0.12 g

 Sorbitan Monolaurate 20 (Tween 20)

 10.00 g

 L-Arginine

 1.00 g

 Methylparaben

 0.10 g

 Propylparaben

 0.05 g

 Demineralized water

 13.73 g

Variations of ± 10% in these quantities are admissible and are mainly due to the origin of the raw materials used and to normal variations typical of the measurements. 5

Girofle is anesthetic and antiseptic.

The therapeutic action of this cream composition is the regeneration of epithelial and vasodilator tissues, also being a local anesthetic. 10

It is of special application in second and third degree burns, ulcers in both venous and arterial lower limbs, bedsores, vasculitic ulcers, post operative scars.

 fifteen

Also, the described IFA is useful for integrating an epidermal healing cream. In a preferred embodiment of this cream composition, each 100 g contains:

Active Pharmaceutical Ingredient (IFA) from approximately 45 g to approximately 55 g

 twenty

Zinc oxide from about 6.3 g to about 7.7 g

Boric acid from about 1.8 g to about 2.2 g

The composition comprises the following pharmaceutically acceptable excipients, carriers and solvents: 30 mol ketostearyl alcohol, ketostearyl alcohol, 25 essence, 20 mol sorbitan monolaurate, methylparaben, propylparaben, and distilled water csp 100 g.

In a preferred form, the composition of the epidermal healing cream according to the present invention is as follows:

 Composition Component

 Quantities

 Oleic acid

 24.37 g

 Palmitic acid

 13.00 g

 Linoleic acid

 7.45 g

 Stearic acid

 4.05 g

 Linolenic acid

 0.55 g

 Vitamin A (as palmitate) 1.7 MUI / g

 0.50 g

 Vitamin E (acetate)

 0.08 g

 Ketostearyl Alcohol (30 moles)

 7.00 g

 Ketostearyl alcohol

 6.00 g

 Zinc oxide

 7.00 g

 Essence

 0.12 g

 Sorbitan Monolaurate 20 (Tween 20)

 10.00 g

 Boric acid

 2.00 g

 Methylparaben

 0.10 g

 Propylparaben

 0.05 g

 Demineralized water

 17.73 g

Variations of ± 10% in these quantities are admissible and are mainly due to the origin of the raw materials used and to normal variations typical of the measurements.

 5

The therapeutic action of the composition is healing of the epidermis. Its main applications are: first degree burns, scoriations, paspas, lesions in the epidermis of any etiology.

Similarly, the IFA described here is useful for preparing an epithelial nourishing cream. In a preferred embodiment of this cream composition, each 100 g contains:

Active Pharmaceutical Ingredient (IFA) from approximately 45 g to approximately 55 g

 5

The composition comprises the following pharmaceutically acceptable excipients, carriers and solvents: 30 mol ketostearyl alcohol, ketostearyl alcohol, essence, 20 mol sorbitan monolaurate, methylparaben, propylparaben, and distilled water csp 100 g.

 10

In a preferred form, the composition of the epithelial nourishing cream according to the present invention is as follows:

 Composition Component

 Quantities

 Oleic acid

 24.37 g

 Palmitic acid

 13.00 g

 Linoleic acid

 7.45 g

 Stearic acid

 4.05 g

 Linolenic acid

 0.55 g

 Vitamin A (as palmitate) 1.7 MUI / g

 0.50 g

 Vitamin E (acetate)

 0.08 g

 Ketostearyl Alcohol (30 moles)

 7.00 g

 Ketostearyl alcohol

 6.00 g

 Essence

 0.12 g

 Sorbitan Monolaurate 20 (Tween 20)

 10.00 g

 Methylparaben

 0.10 g

 Propylparaben

 0.05 g

 Demineralized water

 26.73 g

Variations of ± 10% in these quantities are admissible and are mainly due to the origin of the raw materials used and to normal variations typical of the measurements. 5

Its therapeutic action is to nourish, elasticize and give greater texture to the skin and its main application is to treat crystal skin (epidermolysis bullosa). It is mainly applied to thin skin to provide thickness, moisture and elasticity to the skin.

 10

It is mainly used as a treatment closure of the two previous compositions. All cases treated with the above creams were finished at home for approximately 7-10 days with at least 1 night application per day.

In another application, the IFA disclosed herein is useful for preparing an aerosol healing gel composition. In a preferred embodiment of this healing gel composition, each 100 g contains:

Active Pharmaceutical Ingredient (IFA) from approximately 27 g to approximately 33 g

 twenty

Girofle (clove essential oil) from about 1.8 g to about 2.2 g

The aerosol healing gel composition comprises as a propellant a mixture of isobutane, butane and propane with minor components of other aliphatic saturated hydrocarbons, and the following substances: 30 mol ketostearyl alcohol, ketostearyl alcohol, essence, cyclomethicone, mentyl lactate, monolaurate of sorbitan 20 moles, methylparaben, propylparaben, and distilled water csp 100 g.

In a preferred form, the aerosol healing gel composition according to the present invention is as follows:

 Composition Component

 Quantities

 Oleic acid

 14.62 g

 Palmitic acid

 7.80 g

 Linoleic acid

 4.47 g

 Stearic acid

 2.43 g

 Linolenic acid

 0.33 g

 Vitamin A (as palmitate) 1.7 MUI / g

 0.30 g

 Vitamin E (acetate)

 0.05 g

 Ketostearyl Alcohol (30 moles)

 3.50 g

 Ketostearyl alcohol

 3.00 g

 Girofle (clove essential oil)

 2.00 g

 Cyclomethicone

 0.50 g

 Mentyl lactate

 2.00 g

 Essence

 0.12 g

 Sorbitan Monolaurate 20 (Tween 20)

 10.00 g

 Methylparaben

 0.10 g

 Propylparaben

 0.05 g

 Demineralized water

 48.73 g

Variations of ± 10% in these quantities are admissible and are mainly due to the origin of the raw materials used and to normal variations typical of the measurements. 5

The propellant is a mixture of hydrocarbons of which approximately 15.00 g is used.

The propellant composition is a mixture of isobutane, butane and propane with minor components of other aliphatic saturated hydrocarbons.

Composition ratio: propellant = 100: 15 p / p

Total volume: approximately 200 ml 5

Total weight: about 115 g

It is a self-cooling spray gel composition for first-degree burns, where it acts as a local anesthetic for cold, bacteriostatic disinfectant, organizing and circumscribing the burn to reduce cell injury and regenerating tissue at the same time.

The therapeutic action of the gel is to absorb heat physically and remove it in the form of steam. It has no systemic absorption.

 fifteen

Its main application is in first and second degree burns.

The nasal cavity is covered with epithelium that in certain circumstances becomes inflamed and injured, especially in cases of chronic rhinitis.

 twenty

In yet another application of the IFA disclosed herein, it is useful to formulate a nasal liquid composition for the treatment of lesions of the nasal mucosa. In a preferred embodiment of this nasal liquid composition, each 100 ml contains:

Active Pharmaceutical Ingredient (IFA) from approximately 2.7 g to approximately 3.3 g 25

Methyl lactate from about 0.27 g to about 0.33 g of mentyl lactate

The nasal liquid composition comprises the following pharmaceutically acceptable excipients, carriers and solvents 30: sorbitan monolaurate 20 moles, ketostearyl alcohol 30 moles, ketostearyl alcohol, microcrystalline carboxymethyl cellulose cellulose, xylitol, polysorbate 80, and demineralized water csp 100 ml.

In a preferred form, the nasal liquid composition according to the present invention is as follows:

 Composition Component

 Quantities

 Oleic acid

 1.46 g

 Palmitic acid

 0.78 g

 Linoleic acid

 0.45 g

 Stearic acid

 0.24 g

 Linolenic acid

 0.03 g

 Vitamin A (as palmitate) 1.7 MUI / g

 0.03 g

 Vitamin E (acetate)

 0.01 g

 Ketostearyl Alcohol (30 moles)

 0.50 g

 Ketostearyl alcohol

 0.40 g

 Mentyl lactate

 0.30 g

 Sorbitan Monolaurate 20 (Tween 20)

 1.00 g

 Microcrystalline carboxymethyl cellulose cellulose

 1.00 g

 Xylitol

 7.00 g

 Polysorbate 80

 0.03 g

 Demineralized water

 83.77 g

Variations of ± 10% in these quantities are admissible and are mainly due to the origin of the raw materials used and to normal variations typical of the measurements. 5

The nasal liquid composition is packaged in a nasal spray.

The therapeutic action is that of the regenerator of the nasal mucosa and its main applications are: chronic rhinitis and lesions of the nasal mucosa due to different etiologies. 10

Psoriasis is a chronic autoimmune inflammatory disease of the skin that manifests itself through thickened and inflamed squamous lesions, the clinical and evolution of which is very variable. While it is not contagious, it can be hereditary.

 5

Although it affects any part of the skin, the most frequently affected areas are elbows, knees, scalp, abdomen, back and nails. It is a disease that can cause complications such as psoriatic arthritis.

It has been found that the IFA of the present invention is useful for treating and mitigating the effects of psoriasis if formulated as a cream composition. In a preferred embodiment of this cream composition to treat psoriasis, every 100 g contains:

Active Pharmaceutical Ingredient from approximately 45 g to approximately 55 g 15

Papain 30000 U / mg from about 0.9 g to about 1.1 g

Papain is stabilized in citrus pectin.

The cream composition for treating psoriasis comprises the following pharmaceutically acceptable excipients, carriers and solvents: 30 mol ketostearyl alcohol, 20 ketostearyl alcohol, 20 mol sorbitan monolaurate, essence, citrus pectin, propylene glycol, triethanolamine, methylparaben, propylparaben, and distilled water csp 100 g.

In a preferred form, the cream composition for treating psoriasis according to the present invention is as follows:

 Composition Component

 Quantities

 Oleic acid

 24.37 g

 Palmitic acid

 13.00 g

 Linoleic acid

 7.45 g

 Stearic acid

 4.05 g

 Linolenic acid

 0.55 g

 Vitamin A (as palmitate) 1.7 MUI / g

 0.50 g

 Vitamin E (acetate)

 0.08 g

 Ketostearyl Alcohol (30 moles)

 7.00 g

 Ketostearyl alcohol

 6.00 g

 Papaine 30,000 IU / mg

 1.00 g

 Citrus pectin

 0.35 g

 Propylene glycol

 0.75 g

 Triethanolamine

 0.04 g

 Essence

 0.12 g

 Sorbitan Monolaurate 20 (Tween 20)

 10.00 g

 Methylparaben

 0.10 g

 Propylparaben

 0.05 g

 Demineralized water

 24.59 g

Variations of ± 10% in these quantities are admissible and are mainly due to the origin of the raw materials used and to normal variations typical of the measurements. 5

The therapeutic action is to limit and inhibit dermatitis and desquamation due to psoriasis minimizing them over time. Its application is to treat psoriasis and psoriasiform lesions. Normally, with a nighttime application per day continuously the desired effect is achieved. 10

Smell is a poorly valued sense and, like taste, receives little attention in contemporary physiology and psychology texts. They are described as chemical senses and not proprioceptors. The smell is not only a physiological phenomenon, it is also a moral phenomenon, since odors are considered positive or negative, good or bad. fifteen

In medicine there are symptoms and signs, the symptoms is what the patient describes as discomfort, the sign is something objective that the doctor can perceive, regardless of whether the patient can describe it or not. The smell of old or "noneal" skin in medicine is a sign. 5

The skin or integument is the largest, finest and one of the most important organs in the human body. It forms a self-repairing and protective separation between the internal environment and the outside world. The cutaneous surface of a medium-sized adult is 1.6 to 1.9 m2. Its thickness varies from about 0.05 cm to slightly more than 0.3 cm. The skin and its annexes make up the integumentary system.

Structurally, the skin is a thin, relatively flat organ that forms the cutaneous membrane, composed of two main layers: a thinner exterior, or epidermis, and a thicker internal one, called the dermis. fifteen

The epidermis is made up of several types of epithelial cells. Keratinocytes that constitute more than 90% and form the main structural element of the skin, are filled with a hard, fibrous protein, called keratin. Melanocytes add color to the skin and serve to filter ultraviolet light. Another type of cells, Langerhans cells, 20 play a limited role in the immune reactions that affect the skin and serve as a defense.

The most important function of protection depends largely on the special structural characteristics of the epidermis and on its ability to create and repair itself 25 after an injury or illness. The cells push up from the basal stratum to each successive layer, die, are keratinized and finally shed, continuously. The regeneration time necessary to complete the mitosis, differentiation and movement of new keratinocytes from the basal stratum to the surface of the epidermis, is about 35 days. The process can be accelerated by abrasion of the skin surface. 30

There is a basement membrane, specialized fibrous elements and a unique polysaccharide gel, all useful for attaching the superficial epidermis to the underlying dermis.

The dermis is formed by a thin papillary layer and a thicker reticular layer with a thickness between 0.5 mm and 4 mm depending on the area. In addition to playing a

protective function against mechanical injury and compression, provides mechanical resistance, constituting a storage area for water and important electrolytes. The dermis regenerates itself in a continuous manner, but rapid regeneration of the dermal connective tissue only occurs in unusual circumstances, such as wound healing. 5

In the skin it comprises several fatty acids with the function of impermeability, energy and repair. Fatty acids form phospholipids and glycolipids that are a primary part of the lipid bilayer of the cell membrane.

 10

Over the years, the skin loses elasticity, small wrinkles begin, and a characteristic aroma that is noneal begins to emanate, which is produced by oxidation of palmitoleic acid and vaccine acid produced by bacteria found in the skin. physiological flora of the skin and that, with the passage of time, increase in number. fifteen

So far, beyond the hygienic and health habits, pharmaceutical and cosmetic products are on the market to provide elasticity to the skin such as moisturizers, scrubs and moisturizers.

 twenty

As for the noneal, there are only lotions that aim to lower the content of fatty acids, reducing the amount of oxidation and, consequently, the aroma described.

Unexpectedly, it has been observed that IFA manages to retard skin aging by giving it elasticity, preventing and reducing existing wrinkles and, together with other adjuvants, also decreases the oxidation of fatty acids by controlling the noneal.

With IFA a soap has been formulated that gives vitality, removes dead cells, gives elasticity, and regenerates the skin; It reduces the oxidation of fatty acids because it contains antiseptic, bacteriostatic and activators of the activity of antioxidant enzymes in the skin. Contains new skin oils of great regenerative power that are not found in any known product.

Noneal is treated in this way differently from what is currently established since the few 35 perfumes used for this purpose act by decreasing palmitoleic acid, that is,

inhibiting the natural fatty acids of the skin preventing genuine defense and / or elasticity properties from being maintained.

The proposed product decreases the noneal by acting as a bacteriostatic and antiseptic, considerably reducing the number of bacteria that will produce oxidation and co-help with the content of activators of natural antioxidant enzymes of the skin, that is, the skin enzymes are enhanced so that they inhibit the little oxidation that is going to take place since the bacteria decreased leaving the palmitoleic and vaccine acid intact so that they continue fulfilling their function of permeability and elasticity.

 10

In yet another application of the IFA of the present invention, it is used to formulate a liquid soap composition. In a preferred embodiment of this liquid soap composition, each 100 ml contains:

Active Pharmaceutical Ingredient (IFA) from about 18 g to about 22 g 15 Girofle (clove essential oil) from about 0.09 g to about 0.11 g

Superoxide dismutase from about 1.8 g to about 2.2 g

 twenty

The liquid soap composition comprises the following pharmaceutically acceptable excipients, carriers and solvents: sodium lauryl ether sulfate, citric pectin, triethanolamine, propylene glycol, coconut betaine, ketoestearyl alcohol 30 moles, ketostearyl alcohol, sorbitan monolaurate 20 moles, methylparaben, propylparaben , essence, and distilled water csp 100 ml. 25

In a preferred form, the liquid soap composition according to the present invention is as follows:

 Composition Component

 Quantities

 Oleic acid

 9.75 g

 Palmitic acid

 5.20 g

 Linoleic acid

 2.98 g

 Stearic acid

 1.62 g

 Linolenic acid

 0.22 g

 Vitamin A (as palmitate) 1.7 MUI / g

 0.20 g

 Vitamin E (acetate)

 0.03 g

 Ketostearyl Alcohol (30 moles)

 2.80 g

 Ketostearyl alcohol

 2.40 g

 Superoxide dismutase

 2.00 g

 Citrus pectin

 0.70 g

 Propylene glycol

 1.50 g

 Triethanolamine

 0.08 g

 Essence

 0.30 g

 Sorbitan Monolaurate 20 (Tween 20)

 10.00 g

 Sodium lauryl ether sulfate

 5.00 g

 Coconut Betaine

 1.00 g

 Methylparaben

 0.10 g

 Propylparaben

 0.05 g

 Demineralized water

 54.07 g

Variations of ± 10% in these quantities are admissible and are mainly due to the origin of the raw materials used and to normal variations typical of the measurements. 5

The therapeutic action of the liquid soap composition is as an inhibitor of the reduction of fatty acids, characteristic phenomenon in advanced ages of the human being.

Its applications are the daily hygiene of the elderly for the inhibition of the characteristic smell of the elderly (noneal).

Similarly, with the IFA of the present invention a solid soap or a shower gel can be prepared. 5

As an alternative to the enzyme superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, glutathione reductase or mixtures thereof can be used.

EXAMPLES 10

Example 1: Preparation of the Active Pharmaceutical Ingredient (IFA)

IFA is essentially an oily mixture of fatty acids and essential vitamins with a great capacity to regenerate damaged skin due to various reasons and application in aesthetics to nourish and soften the skin.

In a 316L stainless steel reactor with electric heating and cooling jacket, the solid components of the oil phase were melted and the liquid components were added except the vitamins, mixing until total dissolution reaching 63-65 ° C of temperature. Stirring of the oil mixture was maintained keeping the temperature constant until homogeneous. The oil mixture was cooled by passing water at room temperature through the reactor cooling jacket, constantly stirring the mixture. Vitamins were added below 40 ° C and stirring was maintained until complete homogenization. 25

The IFA obtained comprised every 100 g of oil mixture the following components:

Oleic acid (mp 13 ° C) 48.73 g,

Palmitic acid (mp 63 ° C) 26.0 g,

Linoleic acid (mp -5 ° C) 14.9 g, 30

Stearic acid (mp 69 ° C) 8.1 g,

Linolenic acid (mp -11 ° C) 1.1 g,

Vitamin A (as palmitate) 1.7 MUI / g 1.0 g, and

Vitamin E (as acetate) 0.17 g.

The obtained mixture was taken out of the reactor and packed for later use. 35

Example 2: Form of preparation of an epidermis regenerating cream based on IFA

In a 316L stainless steel reactor with electric heating and cooling jacket, the solid constituents of ketostearyl alcohol and ketostearyl alcohol constituting an oil phase were melted, mixing until total dissolution reaching 52-55 ° C. Stirring of the mixture was maintained keeping the temperature constant until homogeneous. The mixture was cooled by passing water at room temperature through the reactor cooling jacket, constantly stirring the mixture. Below 40 ° C the IFA obtained in Example 1, girofle (clove essential oil) 10 and essence were added, the constant temperature and stirring were maintained until total homogenization, obtaining the oil phase.

The oil phase was poured onto an aqueous phase formed by sorbitan monolaurate 20 (Tween 20), L-arginine, methyl paraben, propyl paraben and demineralized water already prepared by stirring, wherein said aqueous phase was in another stainless steel reactor 316L with water cooling jacket, stirred until cooling to room temperature and formation of a uniform cream.

The oil phase comprised: 20

IFA (Active Pharmaceutical Ingredient) 60.00 g

Ketostearyl alcohol (30 moles) 7.00 g

Ketostearyl Alcohol 6.00 g

Girofle (clove essential oil) 2.00 g

Essence 0.12 g 25

The aqueous phase comprised:

Sorbitan Monolaurate 20 (Tween 20) 10.00 g

L-Arginine 1.00 g

Methyl paraben 0.10 g

Propyl paraben 0.05 g 30

Demineralized water 13.73 g

The pH of the final oil phase-aqueous phase mixture was 7 and was brought to pH 5.5 by adding 1.1 ml of 10% w / w citric acid solution.

The regenerating cream of the epidermis based on the IFA obtained comprised every 100 g of the following components and quantities:

IFA (Active Pharmaceutical Ingredient) 60.00 g

Sorbitan Monolaurate 20 (Tween 20) 10.00 g

Ketostearyl alcohol (30 moles) 7.00 g

Ketostearyl Alcohol 6.00 g

Girofle (clove essential oil) 2.00 g

L-Arginine 1.00 g 5

Essence 0.12 g

Methyl paraben 0.10 g

Propyl paraben 0.05 g

Demineralized water (csp) 13.73 g

 10

Example 3: Form of preparation of an epidermal healing cream based on IFA.

In a 316L stainless steel reactor with electric heating and cooling jacket, the solid constituents of cetostearyl alcohol and ketostearyl alcohol were melted, constituting 30 moles of an oily phase, mixing until completely dissolved reaching 15 52-55 ° C. Stirring of the mixture was maintained keeping the temperature constant until homogeneous. The mixture was cooled by passing water at room temperature through the reactor cooling jacket, constantly stirring the mixture. Below 40 ° C the IFA obtained in Example 1, girofle (clove essential oil) and essence were added, the constant temperature and stirring were maintained until total homogenization, obtaining the oil phase.

The oil phase was poured onto an aqueous phase formed by sorbitan 20 (Tween 20) monolaurate, zinc oxide, boric acid, methyl paraben, propyl paraben and demineralized water already prepared by stirring, where said aqueous phase was in another reactor. 316L stainless steel with water cooling jacket, stirred until cooling to room temperature and formation of a uniform cream.

The oil phase included:

IFA (Active Pharmaceutical Ingredient) 50.00 g 30

Ketostearyl alcohol (30 moles) 7.00 g

Ketostearyl Alcohol 6.00 g

Essence 0.12 g

The aqueous phase comprised:

Sorbitan Monolaurate 20 (Tween 20) 10.00 g 35

Zinc Oxide 7.00 g

Boric acid 2.00 g

Methyl paraben 0.10 g

Propyl paraben 0.05 g

Demineralized water 17.73 g

The pH of the final oil phase-aqueous phase mixture was 7.5 and was brought to pH 5.5 by adding 1.4 ml of 10% w / w citric acid solution.

The epidermal healing cream based on the IFA obtained comprised every 100 g of the following components and amounts:

IFA (Active Pharmaceutical Ingredient) 50.00 g

Sorbitan Monolaurate 20 (Tween 20) 10.00 g 10

Ketostearyl alcohol (30 moles) 7.00 g

Ketostearyl Alcohol 6.00 g

Zinc Oxide 7.00 g

Boric acid 2.00 g

Essence 0.12 g 15

Methyl paraben 0.10 g

Propyl paraben 0.05 g

Demineralized water 17.73 g

Example 4: Form of preparation of an epithelial nourishing cream based on IFA 20

In a 316L stainless steel reactor with electric heating and cooling jacket, the solid constituents of ketostearyl alcohol and ketostearyl alcohol constituting an oil phase were melted, mixing until total dissolution reaching 52-55 ° C. Stirring of the mixture was maintained while maintaining the constant temperature up to 25 homogeneity. The mixture was cooled by passing water at room temperature through the reactor cooling jacket, constantly stirring the mixture. Below 40 ° C the IFA obtained in Example 1 and an essence were added, the constant temperature and stirring were maintained until total homogenization, obtaining the oil phase. 30

The oil phase was poured onto an aqueous phase formed by sorbitan monolaurate 20 (Tween 20), methyl paraben, propyl paraben and demineralized water already prepared by stirring, wherein said aqueous phase was in another 316L stainless steel reactor with cooling jacket by water, it was stirred until cooling to room temperature and formation of a uniform cream.

The oil phase included:

IFA (Active Pharmaceutical Ingredient) 50.00 g

Ketostearyl alcohol (30 moles) 7.00 g

Ketostearyl Alcohol 6.00 g

Essence 0.12 g 5

The aqueous phase comprises:

Sorbitan Monolaurate 20 (Tween 20) 10.00 g

Methyl paraben 0.10 g

Propyl paraben 0.05 g

Demineralized water 26.73 g 10

The pH of the final oil phase-aqueous phase mixture was 7 and was brought to pH 5.5 by adding 1.1 ml of 10% w / w citric acid solution.

The epithelial nourishing cream based on the IFA obtained comprised every 100 g of the following components and amounts:

IFA (Active Pharmaceutical Ingredient) 50.00 g 15

Sorbitan Monolaurate 20 (Tween 20) 10.00 g

Ketostearyl alcohol (30 moles) 7.00 g

Ketostearyl Alcohol 6.00 g

Essence 0.12 g

Methyl paraben 0.10 g 20

Propyl paraben 0.05 g

Demineralized water 26.73 g

Example 5: Form of preparation of a cream to treat psoriasis based on IFA

 25

In a 316L stainless steel reactor with electric heating and cooling jacket, the solid constituents of ketostearyl alcohol and ketostearyl alcohol constituting an oil phase were melted, mixing until total dissolution reaching 52-55 ° C. Stirring of the mixture was maintained keeping the temperature constant until homogeneous. The mixture was cooled by passing water at room temperature through the reactor cooling jacket, constantly stirring the mixture. Below 40 ° C the IFA obtained in Example 1 and an essence were added, the constant temperature and stirring were maintained until total homogenization, obtaining the oil phase.

 35

The oil phase was poured onto an aqueous phase formed by sorbitan monolaurate 20 (Tween 20), methyl paraben, propyl paraben and demineralized water already prepared by stirring, wherein said aqueous phase was in another 316L stainless steel reactor with cooling jacket by water, it was stirred until cooling to 25 ° C and an emulsion phase prepared in a 316L 5 stainless steel emulsifier where papain, citric pectin, propylene glycol and triethanolamine was emulsified was added to the cream formed. Cooling was maintained at room temperature until a uniform cream formed.

The oil phase included:

IFA (Active Pharmaceutical Ingredient) 50.00 g 10

Ketostearyl alcohol (30 moles) 7.00 g

Ketostearyl Alcohol 6.00 g

Essence 0.12 g

The aqueous phase comprised:

Sorbitan Monolaurate 20 (Tween 20) 10.00 g 15

Methyl paraben 0.10 g

Propyl paraben 0.05 g

Demineralized water 24.59 g

The emulsion phase included:

Papain 30000 U / mg 1.00 g 20

Propylene Glycol 0.75 g

Citrus Pectin 0.35 g

Triethanolamine 0.04 g

The pH of the final oil phase-aqueous phase mixture was 7 and was brought to pH 5.5 by adding 1.1 ml of 10% w / w citric acid solution. 25

The cream to treat psoriasis based on IFA comprised every 100 g of the following components and amounts:

IFA (Active Pharmaceutical Ingredient) 50.00 g

Sorbitan Monolaurate 20 (Tween 20) 10.00 g

Ketostearyl alcohol (30 moles) 7.00 g 30

Ketostearyl Alcohol 6.00 g

Papain 30000 U / mg 1.00 g

Propylene Glycol 0.75 g

Citrus Pectin 0.35 g

Essence 0.12 g 35

Methyl paraben 0.10 g

Propyl paraben 0.05 g

Triethanolamine 0.04 g

Demineralized water 24.59 g

Example 6: Form of preparation of a liquid soap to treat the noneal based on 5 IFA

In a 316L stainless steel reactor with electric heating and cooling jacket, the solid constituents of ketostearyl alcohol and ketostearyl alcohol constituting an oil phase were melted, mixing until total dissolution reaching 10 52-55 ° C. Stirring of the mixture was maintained keeping the temperature constant until homogeneous. The mixture was cooled by passing water at room temperature through the reactor cooling jacket, constantly stirring the mixture. Below 40 ° C the IFA obtained in Example 1, girofle and an essence were added, the constant temperature and stirring were maintained until total homogenization, obtaining the oil phase.

The oil phase was poured onto an aqueous phase formed by 25% sodium lauryl ether sulfate, coconut betaine, sorbitan monolaurate 20 (Tween 20), methyl paraben, propyl paraben and demineralized water already prepared by stirring, wherein said aqueous phase was It was in another 20 316L stainless steel reactor with water cooling jacket, stirred until cooling to 25 ° C and the emulsion phase prepared in a 316L stainless steel emulsifier where the peroxide dismutase was emulsified with citrus pectin, propylene glycol and triethanolamine. Cooling was maintained at room temperature until a uniform liquid soap formed. 25

The oil phase included:

IFA (Active Pharmaceutical Ingredient) 20.00 g

Ketostearyl alcohol (30 moles) 2.80 g

Ketostearyl Alcohol 2.40 g 30

Girofle (clove essential oil) 0.10 g

Essence 0.30 g

The aqueous phase comprised:

Lauryl Ether Sodium Sulfate 25% 30.00 g

Coconut betaine 1.00 g 35

Sorbitan Monolaurate 20 (Tween 20) 1.00 g

Methyl paraben 0.10 g

Propyl paraben 0.05 g

Demineralized water 37.97 g

The emulsion phase included:

Superoxide dismutase 2.00 g 5

Propylene Glycol 1.50 g

Citrus Pectin 0.70 g

Triethanolamine 0.08 g

The pH of the final oil-aqueous phase-emulsion phase mixture was 8.5, and was brought to pH 5.5 by adding 2.1 ml of 10% w / w citric acid solution. 10

The liquid soap to treat the noneal based on the IFA obtained comprised every 100 g of the following components and quantities:

Lauryl Ether Sodium Sulfate 25% 30.00 g

IFA (Active Pharmaceutical Ingredient) 20.00 g

Ketostearyl alcohol (30 moles) 2.80 g 15

Ketostearyl Alcohol 2.40 g

Superoxide dismutase 2.00 g

Propylene Glycol 1.50 g

Coconut Betaine 1.00 g

Sorbitan Monolaurate 20 (Tween 20) 1.00 g 20

Citrus Pectin 0.70 g

Essence 0.30 g

Girofle (clove essential oil) 0.10 g

Methyl paraben 0.10 g

Triethanolamine 0.08 g 25

Propyl paraben 0.05 g

Demineralized water 37.97 g

Example 7: Debrident composition based on papain encapsulated in pectin according to prior art 30

In the following Examples of application the following gel debriding composition was used in the prior art:

 35

 Composition Component

 Quantities

 Papaine 30,000 IU / mg

 20.00 g

 Citrus pectin

 7.00 g

 Propylene glycol

 15.00 g

 99% Triethanolamine

 0.723 g

 TW80 (polyoxyethylene sorbitan monooleate (20 OE)

 1.00 g

 KH2PO4

 0.0378 g

 Na2HPO4

 0.1283 g

 Toluidine blue 1% w / w in distilled water

 0.20 g

 Methylparaben

 0.10 g

 Propylparaben

 0.05 g

 Distilled water

 Csp 100 g

APPLICATION EXAMPLES

Application Example 1

 5

It corresponds to a 72-year-old patient with rheumatoid arthritis who has a vasculitis lesion at the distal end of the index finger of the left hand.

The wound was treated with the epidermis regenerating cream according to the present invention. Figure 1a shows the wound at the start of treatment and Figure 1b shows the same wound 10 after 12 hours of treatment with said cream.

The process was painless and the wound was washed with physiological serum.

 fifteen

Application Example 2

This case corresponds to a 65-year-old patient with a contact dermatitis lesion below and between the index finger and the thumb on the back of the left hand.

 5

The treatment with the epidermis regenerating cream according to the present invention was applied.

Figure 2a shows the wound before performing the treatment and Figure 2b shows the same wound after two cures with said epidermis regenerating cream. 10

The treatment was painless and the wound treated only with physiological serum was washed.

Application Example 3

 fifteen

A 25-year-old patient was treated with significant elbow scoria resulting from a motorcycle crash. See the wound before treatment in Figure 3a.

The epidermis regenerating cream of the present invention was applied after washing with physiological serum.

At 24 hours after the start of the treatment, wound healing can be seen as shown in Figure 3b. The treatment was painless.

Application example 4 25

This is a 65-year-old patient with ulcer in a remnant lower limb due to surgery to remove a tumor. In Figure 4a the wound can be seen after 6 months of evolution without having completely closed.

 30

After 25 days of daily treatment with the epidermis regenerating cream according to the present invention, the result shown in Figure 4b was achieved.

A papain gel composition was previously applied to debride by subsequently washing with physiological serum only. 35

Application Example 5

This case corresponds to a 23-year-old patient with lower maxillary scoria due to a motorcycle fall. Figure 5a shows the initial state of the wound before treatment with the epidermis regenerating cream according to the present invention. 5

Initially a debridement treatment was carried out with a papain gel composition and in Figure 5b the result obtained after one hour is observed.

Figure 5c shows the same wound at 12 hours after treatment with the epidermis regenerating cream of the present invention.

The treatment was painless and the wound treated only with physiological serum was washed.

Application example 6 15

A 6-year-old patient was treated with a motorcycle burn burn in a lower limb. Figure 6a shows the wound with 72 hours of evolution.

Figure 6b shows the same wound after 1 hour of treatment with a papain debriding gel 20.

Figure 6c shows the result after 24 hours of a single application of the epidermis regenerating cream of the present invention.

 25

Application Example 7

Figure 7a shows the left shoulder of a 35-year-old patient with a scum generated by a motorcycle crash.

 30

Figure 7b shows the same wound after one hour of treatment with a debriding composition in papain gel.

The treatment was painless and was only washed with physiological serum after debridement treatment. 35

Figure 7c shows the same wound at 24 hours after a single cure with the epidermis regenerating cream according to the present invention.

Application example 8 5

A 27-year-old patient was treated with several scars on his left wrist due to a motorcycle crash. Figure 8a shows the wound before treatment.

A debridement treatment was carried out with a papain gel composition for 10 an hour and then two cures were performed with the epidermis regenerating cream according to the present invention. At 48 hours the wound presented the appearance shown in Figure 8b.

It can be noted that smaller scoriations that were not treated remain intact 15 as in the first photograph of Figure 8a.

Application Example 9

A 36-year-old patient was treated with peripheral vasculopathy in the right forearm. twenty

Figure 9a shows the lesions present in the limb, 3 ulcers of a month of evolution despite treatment with silver sulfadiazide.

Figure 9b shows the ulcers after 5 days of treatment comprising a daily cure with the epidermal healing cream according to the present invention.

It is observed how the cream applied produces a change of skin texture from the peripheral area to the lesions. The treatment was painless using only physiological serum to wash the wounds when necessary. 30

Application Example 10

A patient with a second degree burn who was treated for two days with the epidermis regenerating cream according to the present invention is shown in Figure 10a.

Figure 10b shows how the epidermal healing cream according to the invention was applied throughout the wound.

Figure 10c shows the result of treatment at 24 hours, where the wound is already 5 with epidermis.

Application Example 11

Figure 11a shows a limb with lesions due to psoriasis of a 10 50 year old patient.

A treatment is carried out by applying the cream composition to treat psoriasis according to the present invention.

 fifteen

Figure 11b shows the evolution of psoriatic lesions after 24 treatment with said composition.

Application Example 12

 twenty

Figure 12a shows a limb with lesions due to psoriasis of a 55-year-old female patient.

A treatment is carried out by applying the cream composition to treat psoriasis according to the present invention. 25

Figure 12b shows the evolution of psoriatic lesions after 24 treatment with said composition.

Application example 13 30

Figure 13a shows a limb with lesions due to crystal skin of a 10-year-old female patient.

A treatment is carried out by applying the epithelial nourishing cream composition 35 to treat glass skin according to the present invention.

Figure 13b shows the evolution of crystal skin lesions after 3 days of starting a treatment with said composition, showing a large decrease in the lesion.

 5

Application Example 14

A group of 20 elderly people between 70 and 85 years old, half men and half women, who had a characteristic odor of cetans by oxidation of fatty acids from the skin despite being sanitized with traditional cosmetic products such as soaps, 10 lotions and perfumes, were treated with the liquid soap composition according to the present invention.

The treatment consisted of a daily bath using the liquid soap composition according to the present invention for a week that caused the gradual decrease up to 15 total disappearance of the noneal odor within that period.

The treatment was continued by performing periodic baths for a month. The effect achieved was maintained with two weekly baths using the liquid soap composition of the invention. twenty

Examples of application of the epithelial nourishing cream composition

The epithelial nourishing cream composition is used for the treatment of lesions in patients with crystal skin and to complete and / or complement the treatments where the epidermis regenerating cream composition and / or the epidermal healing cream composition was applied .

Once the treatment with the aforementioned epidermis regenerating cream and / or epidermal healing cream compositions is completed, the patient is treated for a longer period that can range from a couple of weeks to one or two months depending on the severity of their injuries

In all cases of Application Examples 1 to 10, the closure treatment with the epithelial nourishing cream composition was applied and a very effective response and evolution was observed.

favorable, much greater than that normally observed in similar cases using other creams, ointments and ointments from the state of the art.

In the Example of application 13, a lesion was treated in a patient with glass skin of 30 days of evolution and at 3 days of treatment with the composition of the present invention 5 a great decrease in the lesion was visualized.

Comparative examples

Given the tests performed that are exemplified in Application Examples 1 to 10, it is proposed as comparative examples of effectiveness those where the patient came from a traditional treatment with a composition of the state of the art without result or with result of lean effectiveness and passed to a treatment using a composition of the present invention comprising the IFA described herein.

 fifteen

In particular, reference is given to Application Example 1, corresponding to a 72-year-old patient with a vasculitis lesion in the index finger of the left hand that did not heal with traditional treatments; to Application Example 2, corresponding to a 65-year-old patient with a contact dermatitis lesion on the back of his left hand who also did not respond satisfactorily to traditional treatment; to Application Example 4, 20 in which a 65-year-old patient with ulcer in a lower limb by surgery where the wound after 6 months of evolution had not healed completely; to Application Example 9, where the patient came from a month of evolution without positive results despite treatment with silver sulfadiazide; and to the Application Example 14, where a group of elderly people had a characteristic smell of noneal despite being sanitized with 25 traditional cosmetic products and which were treated with the liquid soap composition according to the present invention with satisfactory results.

In all these cases the patients had been carrying out a treatment without a positive result using any of the prior art compositions, and then changing the treatment 30 using the same IFA compositions of the present invention, achieving a positive result in much less time. .

35

Claims (30)

1. An oily active pharmaceutical ingredient (IFA) for the treatment of skin conditions, CHARACTERIZED because it comprises: Oleic acid from about 35 to about 55 g, Palmitic acid from about 15 to about 32 g, Linoleic acid from about 10 to about 20 g, Stearic acid from about 7.5 to about 9 g, Linolenic acid from about 0.5 to about 1.5 g, 10 Vitamin A (as palmitate) 1.7 MUI / g from about 0.8 to about 1.2 g, and Vitamin E (as acetate) from about 0.1 to about 0.24 g. 2. The active pharmaceutical ingredient (IFA) of claim 1, CHARACTERIZED 15 because it comprises: Oleic acid approximately 48.73 g, Palmitic acid approximately 26.0 g, Linoleic acid approximately 14.9 g, Stearic acid approximately 8.1 g, 20 Linolenic acid approximately 1.1 g, Vitamin A (as palmitate) 1.7 MUI / g approximately 1.0 g, and Vitamin E (as acetate) approximately 0.17 g. 3. A CHARACTERIZED epidermis regenerating cream composition because it comprises from about 54 g to about 66 g of the active pharmaceutical ingredient (IFA) of claim 1 or 2, from about 0.9 to about 1.1 g of L-arginine, and from about 1.8 to about 2.2 g of girofle (clove essential oil), together with pharmaceutically acceptable excipients, carriers and solvents. 30 4. The epidermis regenerating cream composition of claim 3, CHARACTERIZED in that the pharmaceutically acceptable excipients, carriers and solvents are 30 mol ketostearyl alcohol, ketostearyl alcohol, essence, 20 mol sorbitan monolaurate, methylparaben, propylparaben, and distilled water csp 100 35 g 5. Use of the active pharmaceutical ingredient (IFA) of claim 1 or 2, CHARACTERIZED because it is to prepare a pharmaceutical composition for the regeneration of epithelial tissues, vasodilator and local anesthetic.  5 6. The use of claim 5, CHARACTERIZED in that the application is in second and third degree burns, ulcers in both venous and arterial lower limbs, bedsores, vasculitic ulcers, and post operative scars. 7. A CHARACTERIZED epidermal healing cream composition in that it comprises from about 45 g to about 55 g of the active pharmaceutical ingredient (IFA) of claim 1 or 2, from about 6.3 g to about 7.7 g of zinc oxide, and from about 1.8 g to about 2.2 g of boric acid, together with pharmaceutically acceptable excipients, carriers and solvents.  fifteen 8. The epidermal healing cream composition of claim 7, CHARACTERIZED in that the pharmaceutically acceptable excipients, carriers and solvents are 30 mol ketoestearyl alcohol, cetostearyl alcohol, essence, 20 mol sorbitan monolaurate, methylparaben, propylparaben, and distilled water csp 100 g . twenty 9. Use of the active pharmaceutical ingredient (IFA) of claim 1 or 2, CHARACTERIZED because it is to prepare a pharmaceutical composition for epidermis healing application.  25 10. The use of claim 9, CHARACTERIZED in that the application in epidermis healing is in first degree burns, scoriations, paspas, and lesions in the epidermis of any etiology. 11. A CHARACTERIZED epithelial nourishing cream composition comprising 30 from about 45 g to about 55 g of the active pharmaceutical ingredient (IFA) of claim 1 or 2, together with pharmaceutically acceptable excipients, carriers and solvents. 12. The epithelial nourishing cream composition of claim 11, characterized in that the pharmaceutically excipients, carriers and solvents Acceptable are 30 mol ketostearyl alcohol, ketostearyl alcohol, essence, 20 mol sorbitan monolaurate, methylparaben, propylparaben, and distilled water csp 100 g. 13. Use of the active pharmaceutical ingredient (IFA) of claim 1 or 2, 5 CHARACTERIZED because it is for preparing an epithelial nourishing cream composition for application in nutrition, elasticization and skin texturing. 14. The use of claim 13, CHARACTERIZED in that the application is in crystal skin (bullous epidermolysis). 10 15. A CHARACTERIZED aerosol healing gel composition in that it comprises from about 27 g to about 33 g of the active pharmaceutical ingredient (IFA) of claim 1 or 2, and from about 1.8 g to about 2.2 g of girofle (essential oil of clove), together with pharmaceutically acceptable excipients, carriers and solvents. 16. The aerosol healing gel composition of claim 15, CHARACTERIZED in that the pharmaceutically acceptable excipients, carriers and solvents are a mixture of isobutane, butane and propane with components smaller than 20 other saturated aliphatic hydrocarbons as propellant and the following ketostearyl alcohol substances 30 moles, ketostearyl alcohol, essence, cyclomethicone, mentyl lactate, sorbitan monolaurate 20 moles, methylparaben, propylparaben, and distilled water csp 100 g.  25 17. Use of the active pharmaceutical ingredient (IFA) of claim 1 or 2, CHARACTERIZED because it is for preparing a pharmaceutical composition for application in first and second degree burns. 18. The use of claim 17, CHARACTERIZED in that the application is as a local anesthetic for first and second degree burns, bacteriostatic disinfectant, decrease in cell injury and tissue regeneration. 19. A nasal liquid composition CHARACTERIZED in that it comprises from about 2.7 g to about 3.3 g of the active pharmaceutical ingredient (IFA) of claim 1 or 2, and from about 0.27 g to about 0.33 g of Methyl lactate, together with pharmaceutically acceptable excipients, carriers and solvents. 20. The nasal liquid composition of claim 19, CHARACTERIZED in that the pharmaceutically acceptable excipients, carriers and solvents are 5 sorbitan 20 mol monolaurate, 30 mol ketostearyl alcohol, carboxymethyl cellulose microcrystalline alcohol, xylitol, polysorbate 80, and demineralized water csp 100 ml 21. Use of the active pharmaceutical ingredient (IFA) of claim 1 or 2, 10 CHARACTERIZED because it is to prepare a pharmaceutical composition for application as a nasal mucosa regenerator. 22. The use of claim 21, CHARACTERIZED because the application is in chronic rhinitis and lesions of the nasal mucosa due to different etiologies. fifteen 23. A cream composition for treating CHARACTERIZED psoriasis because it comprises from about 45 g to about 55 g of the active pharmaceutical ingredient (IFA) of claim 1 or 2, and from about 0.9 g to about 1.1 g of papain 30,000 U / mg, together with pharmaceutically acceptable excipients, carriers and solvents. 24. The cream composition for treating psoriasis of claim 23, CHARACTERIZED in that the pharmaceutically acceptable excipients, carriers and solvents are 30 mol ketostearyl alcohol, ketostearyl alcohol, 25 sorbitan 20 mol monolaurate, essence, citrus pectin, propylene glycol, triethanolamine, methylparaben , propylparaben, and distilled water csp 100 g. 25. Use of the active pharmaceutical ingredient (IFA) of claim 1 or 2, CHARACTERIZED because it is to prepare a pharmaceutical composition for application as a limiting and inhibitor of dermatitis and desquamation by psoriasis. 26. The use of claim 25, CHARACTERIZED because the application is in psoriasis and psoriasiform lesions.  35 27. A liquid soap composition CHARACTERIZED in that it comprises from about 18 g to about 22 g of the active pharmaceutical ingredient (IFA) of claim 1 or 2, from about 0.09 g to about 0.11 g of girofle (clove essential oil of odor), and about 1.8 g to about 2.2 g of superoxide dismutase, together with pharmaceutically acceptable excipients, carriers and solvents. 28. The liquid soap composition of claim 27, CHARACTERIZED in that the pharmaceutically acceptable excipients, carriers and solvents are sodium lauryl ether sulfate, citric pectin, triethanolamine, propylene glycol, coconut betaine, 30 mol ketostearyl alcohol, ketostearyl alcohol, monolaurate of sorbitan 20 moles, methylparaben, propylparaben, essence, and distilled water csp 100 ml. 29. Use of the active pharmaceutical ingredient (IFA) of claim 1 or 2, CHARACTERIZED because it is to prepare a pharmaceutical composition for use as a liquid soap inhibitor of fatty acid reduction, characteristic phenomenon in advanced ages of the human being. 30. The use of claim 29, CHARACTERIZED in that the application is in daily sanitation of the elderly to inhibit the characteristic smell of the elderly. twenty