Topical composition of sclerosing agents in aqueous carriers

Abstract

The present invention relates to a topical composition with sclerosing agents, composed of a chemical sclerosing agent, an osmotic sclerosing agent and methylrosaniline chloride in an aqueous carrier, having antifungal and antimicrobial properties, as well as a process for preparing the invention, and the use of same in the treatment of injuries caused in the hypodermis, epidermis and dermis, such as contusions, incised wounds and sharps injuries, first, second and third degree burns, grade 1, 2 and 3 ulcers, varicose ulcers, arthritis ulcers, pressure ulcers, diabetic foot ulcers, as well as in any cutaneous ecosystem.

Description

[0001] TOPICAL COMPOSITION OF SCLEROSING AGENTS IN AQUEOUS CARRIERS

[0002] HISTORICAL BACKGROUND

[0003] Sugars

[0004] The first instance of the use of sugar in wound healing was reported in the late 1800s at the University of Strasbourg (France) and in Latin American countries such as Chile, Bolivia, Brazil, and Peru. 14 Herszage 15 described his early experiences with the use of this substance in various animal and human conditions.

[0005] Honey is the supersaturated, sugary, and viscous solution produced by bees when they ingest nectar from flowers and sugary juices from other parts of the plant, as well as the sweet secretions of aphids, to enrich it with substances from their own bodies. Depending on its origin, honey can be unifloral, multifloral, or nonfloral if the nectar comes from sweet insect secretions.

[0006] Sugars not only promote healing through their action on cell division, collagen synthesis and maturation, as well as wound contraction and epithelialization, but also improve nutritional balance. In addition to the aforementioned properties, they contain an antibacterial factor due to their high antioxidant content, which protects tissue from the action of free radicals. They are also attributed with anti-inflammatory properties, as they reduce edema, exudate, and local pain.

[0007] On the other hand, honey's acidity below pH 4 favors the antimicrobial action of macrophages, since an acidic pH within the vacuole is associated with bacterial lysis. As mentioned, the high sugar content prevents bacterial growth (osmolarity) and, in turn, reduces the formation of toxic ammonia. On this basis, acidification accelerates healing and provides a local energy source, forming a protective protein layer over the wound. The acidity strengthens the action of macrophages.

[0008] Numerous studies have been conducted on the effects of honey and sugars, not only on acute and chronic wounds, whether infected or not, but also on venous ulcers, bedsores, and other infections, confirming the antibacterial and wound-healing properties of this substance. In a clinical trial, Al-Waili randomly assigned 27 participants with infected wounds from cesarean section or hysterectomy to receive twice-daily applications of honey or an antiseptic wash containing 70% ethanol and povidone-iodine, in addition to systemic antibiotics, depending on their group. However, the average healing time was shorter in those treated with the natural product.

[0009] In another study, 28 of the participants presented with ulcers, chronic osteomyelitis, abscesses, traumatic or postoperative wounds, and sugar dressings were the comparator treatment. The mean time to complete healing was 31.5 days in those treated with honey and 56 in those receiving sugar. Manuka honey, a monofloral substance derived from Leptospermum tree species in New Zealand and Australia, has attracted particular interest because, independent of the peroxide effect and osmolarity of honey, it has antibacterial properties. However, honey exerts an antimicrobial action equivalent to a similar percentage as phenolic acid in the solution.

[0010] Water activity is the minimum concentration of water required in a microorganism's environment for reproduction. Sugar creates an environment with high osmolarity or low water content, since water and lymph migrate out of the tissue toward the sugar solution, thereby inhibiting bacterial growth.

[0011] In turn, lymph provides nutrients to the tissue structure, attracting macrophages (which participate in "wound cleansing"), accelerating the shedding of devitalized and necrotic tissue, providing a local energy source, and forming a protective protein layer over the wound. It also has deodorizing properties, as bacteria use glucose instead of amino acids for their metabolism, and produce lactic acid instead of malodorous elements (ammonium, amines, and sulfur compounds).

[0012] In general, the antibacterial activity of granulated sugar is based on the dehydration that occurs in the bacterial cytoplasm, which achieves both lysis of the microorganism and, on the other hand, the reproductive inability of unused bacteria. This process is related to a physical property of sugar, consisting of its low water activity, which conditions a high osmolarity in the extracellular space and generates plasmolysis or death of the germ. This water activity of sugar does not affect infected tissue cells because they are exposed one after the other. It only conditions the migration of water, lymph, and blood from the depths of the tissue to the surface where the sugar is located.

[0013] In international patent WO 2010 / 028257, sustained-release formulations using non-aqueous carriers were used for the treatment of diabetes. Microspheres formed from biopolymers containing 2% exenatide and sugar are formulated as the active ingredient, where the non-aqueous carrier is fatty acid esters. However, the technique used is injectable for the exclusive treatment of diabetes, and sugar is not found as a healing agent.

[0014] Another background to highlight on the use of glucose is in a patent with file number MX / a / 2018 / 015203 where it was used in the treatment of varicose veins and diabetic foot in sclerotherapy where sclerosing agents are injected directly into the varicose vein; which are substances of different chemical composition that aim to produce an injury in the venous wall or fibrosis, and generate a regression of the vein and fibrosis of it, however it is not used topically for the treatment of skin wounds.

[0015] Sclerosing agents

[0016] Sclerosing agents are divided into three types: Detergents, Chemical Agents and Osmotics.

[0017] Detergents

[0018] They interact with the lipid layer of the endothelial cell. The detergent's nonpolar group aligns with that of the cell membrane, reducing the surface tension that disrupts the cell. The most commonly used are: Polidocanol, sodium tetradecyl sulfate, ethanolamine oleate, and sodium morrhuate.

[0019] Chemical Agents

[0020] They exert a direct toxic effect on the endothelium. The most commonly used are: chromated glycerin, sodium salicylate, and polyiodinated iodine.

[0021] Osmotics

[0022] They cause dehydration and cell destruction by lysis. The most commonly used are: hypertonic saline solution, saline dextrose solution, 20% sodium chloride, 12-60% sodium salicylate, and 50% hypertonic glucose (sugar).

[0023] In this regard, it was found that glucose is an osmotic sclerosant responsible for producing dehydration and cell destruction by lysis. These antecedents specify the use of honey, sugar or glucose. Regarding sodium salicylate, we find in international patent WO 2005 / 063269 where it is used as an antithrombotic agent, where an aqueous extract of red vine leaves is administered in the form of oral capsules for the treatment or prevention of mild to moderate chronic venous insufficiency in the legs. However, it is a novelty that is used orally to prevent complications of CVI, but does not treat the complications that can arise such as varicose ulcers and larger varicose veins.

[0024] On the other hand, we have international patent WO 2014 / 195872, characterized in that the composition is an antifungal shampoo, which generally relates to particles comprising an active agent and one or more lipids and / or proteins and / or carbohydrates and / or cationic molecules. However, the carrier agent is non-aqueous fatty acids.

[0025] Therefore, there remains a need in the field of compositions to find suitable and effective active agents for the treatment of skin wounds, such as bruises, incised wounds, puncture wounds, first-, second-, and third-degree burns, grade 1, 2, and 3 ulcers, varicose vein ulcers, arthritis ulcers, pressure ulcers, diabetic foot ulcers, or any other cutaneous ecosystem. This is also due to the need to find an appropriate application technique that is free of complications and adverse effects.

[0026] DETAILED DESCRIPTION

[0027] The invention provides a topical composition of sclerosing agents composed of a chemical sclerosing agent, an osmotic sclerosing agent, and methylrosaniline chloride in an aqueous carrier with antifungal and antimicrobial properties, as well as a process for preparing said invention. This solution acts through the chemical sclerosing agent, exerting an irritating effect and clearing the lesion. In turn, the osmotic sclerosing agent produces dehydration and cell destruction by lysis, creating fibrosis that allows healing.

[0028] The term “lesion” refers to any condition or disorder in the cutaneous system

[0029] The description provides a suitable medication for the treatment of injuries in patients caused in the hypodermis, epidermis, and dermis. These include bruises, incised wounds, puncture wounds, first-, second-, and third-degree burns, grade 1, 2, and 3 ulcers, varicose vein ulcers, arthritis ulcers, pressure ulcers, and diabetic foot ulcers, as well as those throughout the cutaneous ecosystem.

[0030] The term "patient" refers to mammals, including humans, pets, farm animals, zoo animals, or the like. In one embodiment, the patient is a human.

[0031] The terms “treat” or “treatment” refer to the administration of one or more active pharmaceutical ingredients to a patient who has a disorder, condition, or predisposition to a condition or disease, for the purpose of alleviating, diminishing, remedying, mitigating, ameliorating, slowing, or halting the progress or worsening of the disease, or at least a symptom of the disease, condition, or disorder, or the predisposition to a condition or disorder.

[0032] The topical composition stimulates the healing of a lesion by covering the wound with a layer of an osmotic sclerosing agent that acts as an antibacterial acid protector, promoting dehydration and cell destruction by lysis.

[0033] An additional advantage is that it helps provide antifungal protection, together with the chemical sclerosing agent, it exerts an irritating effect that maintains active vasodilation allowing the wound to be cleaned and irritated so that in synergy with the osmotic sclerosing agent it generates a prompt cellular recovery in the affected tissue.

[0034] Another added benefit is that the aqueous carrier allows the presence of other minerals to eliminate excessive fluid accumulation in the tissues, promoting more effective healing by forming, within a couple of days, a secondary elementary lesion produced by the drying of an exudate or secretion, and covering it with new tissue until the exposed wound is eliminated.

[0035] In patent application MX / a / 2018 / 015203, the activity it exerted when infiltrated in varicose veins, promoting fibrosis, was observed. This motivated the inventive activity of applying it topically, surprisingly finding a second use for said solution. Where the sclerosing agent glucose promoted dehydration and cell destruction by lysis in the circulatory system. It was observed that blood glucose acts as a thickener, producing fibrosis (scarring) in the veins. It was concluded that the healing active ingredient is said active ingredient.

[0036] In one embodiment, an attempt was made to achieve the density of honey with a low percentage of water, thus achieving its viscosity, but the effects were minimal, as it was observed that hydrogen and oxygen molecules are essential for effective healing.

[0037] In several modalities, it was observed that the use of saline solutions or solutions containing other types of minerals, as well as fatty acids, promoted fluid retention, maintaining moisture in the lesion, delaying dehydration and cell destruction by lysis.

[0038] In additional modalities using the osmotic agent alone, healing was slower; it was also observed that once applied within five minutes, the wound was more effective, with blood flow being observed to play an important role in healing.

[0039] An additional advantage is that when a topical composition is used to treat a wound, a portion of the osmotic sclerosing agent material comes into contact with blood to accelerate clotting. Furthermore, when the wound is exposed to the chemical sclerosing agent, it exerts a vasodilatory effect, allowing more osmotic molecules to come into contact with the damaged tissues.

[0040] In one embodiment, the composition may be used in combination with an anesthetic solution.

[0041] Compared to the hemostatic devices in patent application WO 2013 / 191836, which use calcium alginate and a fatty acid coated with gauze, they cause cellular hypoxia by promoting a decrease in oxygen to the cells, neglecting the importance of oxygen for cellular recovery. They also use minerals and fatty acids, preventing effective and prompt recovery and ignoring fungal activity. There are formulations with fatty acids that aid in cellular hydration of tissues, but they do not promote effective healing.The topical formulation helps with cellular dehydration of tissues by removing minerals and covering the wound with an acidic layer of glucose to eventually form a secondary elementary lesion produced by the drying of an exudate or secretion, and covering it with new tissue and allowing for more effective and rapid healing. It also treats burns, varicose ulcers, and diabetic ulcers with lower-cost active ingredients.

[0042] An additional advantage after applying the topical formulation is that it generates a tolerable burning sensation of no more than 1 minute, after which the activator acts with an analgesic effect on the affected area.

[0043] It is important to respect the inventive activity that is promoted by encouraging tissue dehydration for cellular regeneration, since various health and industrial sectors promote the treatment of injuries with moist dressings that include washing with soap and water, disinfecting the affected area by applying topical moisturizing ointments, or saline solutions, which further aggravate the condition. Those skilled in the art must strictly emphasize changing the state of the art in the treatment of injuries by promoting tissue dehydration.

[0044] In terms of cost-effectiveness, the wound healing activator displaces invasive or expensive treatments such as patches, ozone therapy, hyperbaric chambers, or graft surgery. Based on the state of the art, it promotes treatment accessibility and can be applied in doctors' offices, health centers, hospitals, and in the comfort of the patient's home. This results in morbidity control and greater access to treatment for individuals.

[0045] The objective of the invention is to implement the invention in the health sector, to eliminate signs and symptoms, and to prevent and treat complications, which is achieved through proper and rapid application.

[0046] Formulation of a Component

[0047] Previous topical formulations containing at least two sclerosing agents. The first sclerosing agent may be a chemical agent, which may be any of the following: chromated glycerin, sodium salicylate, iodine, or a combination of two or more of these. The second sclerosing agent may be an osmotic agent, which may be any of the following: hypertonic saline, hypertonic glucose, dextrose, sodium chloride, or a combination of two or more of these.

[0048] Carrier “Carrier” (or vehicle) refers to a pharmaceutically acceptable aqueous liquid material which may contain one or more compounds.

[0049] The term "aqueous" includes all other amounts of water that do not negatively impact a patient's cutaneous ecosystem. Thus, a composition may contain approximately 0.1% (w / v) water or less than 100% (w / v). The carrier solubilises the sclerosing agents. The carrier also does not cause infection in the cutaneous ecosystem of the patient being treated.

[0050] In one embodiment, the aqueous carrier may be distilled water. In another embodiment, the aqueous carrier may be double-distilled water. In yet another embodiment, the aqueous carrier may be triple-distilled water.

[0051] In another embodiment, the aqueous carrier may contain a gel-forming agent which may be present in an amount that does not cause a gel depot to form at the site of in vivo administration of the formulation. In one embodiment, the pharmaceutically acceptable carrier does not contain a gel-forming agent.

[0052] Pharmaceutically active ingredient

[0053] A pharmaceutically active ingredient is a biologically active compound that has a therapeutic, prophylactic, or other beneficial pharmacological and / or physiological effect on the patient. The pharmaceutically active ingredient may also be a mixture of two or more compounds.

[0054] Chemical sclerosing agent formulations contain from about 0.01% to 30% (w / v). For example, the amount of the pharmaceutically active ingredient may be from about 0.01% to 30% (w / v) of the total weight of the composition. In one embodiment, iodine is used at about 0.01% to 10% (w / v). In another embodiment, sodium salicylate is used at about 0.01% to 10% (w / v).

[0055] Osmotic sclerosing agent formulations contain from about 0.01% to 50% (w / v). For example, the amount of the pharmaceutically active ingredient can be from about 0.01% to 50% (w / v) of the total weight of the composition.

[0056] The amount of the active pharmaceutical ingredient will vary depending on the desired effect, potency of the agent, planned release levels, and the elapsed time over which the ingredient will be released.

[0057] In one embodiment, methylrosaniline chloride may be present in an amount ranging from about 0.01% to about 10% (w / v). For example, the amount of the pharmaceutically active ingredient may be from about 0.01% to about 10% (w / v) of the total weight of the composition. Sugars

[0058] A sugar is a monosaccharide, disaccharide, oligosaccharide, or a derivative thereof. Suitable sugar derivatives are monosaccharide sugar alcohols. Monosaccharides include, but are not limited to, glucose, fructose, and maltose. A disaccharide, as further defined herein, is a compound which, upon hydrolysis, provides two molecules of a monosaccharide. Suitable disaccharides include, but are not limited to, sucrose, lactose, and trehalose. Suitable oligosaccharides include, but are not limited to, ralphose and maltose. The osmotic sclerosing agent may comprise sucrose, glucose, galactose, dextrose, maltose, fructose, mannose, lactose, trehalose, raffinose, acarbose, glycol, glycerol, erythritol, threitol, arabitol, ribitol, sorbitol, dulcitol, iditol, isomalt, malitol, lactitol, mannitol, xylitol, or a combination of two or more thereof. In one embodiment, the sugar is sucrose, glucose, mannose, or fructose.

[0059] The amount of sugar present in the osmotic agent can vary from about 0.01% (w / v) to about 50% (w / v). In one embodiment, it is used at about 30% (w / v).

[0060] PREPARATION METHOD

[0061] A) In a flask add 500 ml of distilled water and boil over low heat for 5 minutes.

[0062] B) Add the selected osmotic sclerosing agent in small portions using a funnel and mix with slow, circular movements until it is completely incorporated and dissolved.

[0063] C) Let the solution boil for 2 minutes, stirring continuously.

[0064] D) Once the osmotic sclerosing agent has dissolved in the distilled water, the chemical sclerosing agent is added and mixed with slow circular movements until it is completely incorporated and dissolved.

[0065] E) Let the solution boil for 2 minutes, stirring continuously. F) Once removed from the heat, pour it into another flask using a funnel and filter it through a medium-pore paper filter.

[0066] G) Once filtered, at room temperature add methylrosaniline chloride and mix with slow circular movements until it is completely incorporated and dissolved.

[0067] H) Once at room temperature, it is poured into an amber bottle.

[0068] APPLICATION METHOD

[0069] 1.-Determine the appropriate area

[0070] 2.- Keep the affected area completely dry.

[0071] 3.- Using a disinfected or sterile latex glove, apply the activator evenly to the affected area.

[0072] 4.- Allow the topical formulation to absorb for one hour or until completely dry.

[0073] 5.- Keep the affected area completely dry and do not wash or perform asepsis.

[0074] 6.- Apply every 6 hours.

[0075] The application medium for administering to the patient and containing the formulation may be the following: atomizer, patch, vial, ampoule, container, cotton, swabs, dropper, container with applicator, solution container, syringe, etc.

[0076] CONTRAINDICATIONS

[0077] - Do not administer orally.

[0078] -Do not administer if the solution is not clear or contains particles in the suspension. - Patient sensitivity or allergy to sugar or glucose.

[0079] -Patient sensitivity or allergy to methylrosaniline chloride

[0080] SALICYLATE INTOLERANCE

[0081] With 2 or 3 grams or less, there are no intolerance symptoms. When intolerance symptoms occur, the patient complains of ringing in the ears, some loss of hearing, vertigo, delirium, and dyspnea. These disorders are due to acidosis or ketosis, which are relieved by ingesting high amounts of sodium bicarbonate.

[0082] TOXICITY

[0083] The lethal dose varies widely, from 12 grams to 30 grams, which is equivalent to 50 ml to 1.5 ml of the solution. In children, it is sometimes less than 12 grams.

[0084] NERVOUS SYSTEM:

[0085] With 4 to 6 grams: Ringing in the ears, floating sensation, noise in the head. All of these phenomena appear up to 2 hours after oral consumption and last up to 6 hours.

[0086] With 8 to 10 grams: Headaches and drunkenness.

[0087] SIDE EFFECTS AND COMPLICATIONS.

[0088] Overall, glucose is a very noble active ingredient, making the procedure safe and well-tolerated, but it is important to warn patients with glucose allergies. EXAMPLES

[0089] The following non-limiting examples provide additional illustrations for making and using the formulations described herein, and are intended to limit the scope of the appended claims.

[0090] EXAMPLE 1

[0091] A topical formulation can be prepared, for example, by selecting iodine as a chemical sclerosing agent, used at about 5% (w / v), and sodium chloride as an osmotic sclerosing agent. Thus, the carrier can be about 100% (w / v) distilled water. In one embodiment, methylrosaniline chloride can be used, which can be present at about 5% (w / v). In another embodiment, methylrosaniline chloride is not used.

[0092] EXAMPLE 2

[0093] In another embodiment, a topical formulation can be prepared, for example, chromated glycerin is selected as a chemical sclerosing agent, which is used at about 5% (w / v), and dextrose is selected as an osmotic sclerosing agent at 25%. Thus, the carrier can be about 100% (w / v) distilled water. In one embodiment, methylrosaniline chloride can be used, which can be present at about 5% (w / v). In another embodiment, methylrosaniline chloride is not used.

[0094] EXAMPLE 3

[0095] In another embodiment, a topical formulation can be prepared, for example, sodium salicylate is selected as a chemical sclerosing agent, which is used at approximately 5% (w / v), and hypertonic glucose is selected as an osmotic sclerosing agent at 5%. Thus, the carrier can be approximately 80% (w / v) distilled water. In one embodiment, methylrosaniline chloride can be used, which can be present at approximately 5% (w / v). In another embodiment, methylrosaniline chloride is not used. EXAMPLE 4

[0096] In another embodiment, a topical formulation can be prepared, for example, sodium salicylate is selected as a chemical sclerosing agent, which is used at about 5% (w / v), and sodium chloride is selected as an osmotic sclerosing agent at 5%. Thus, the carrier can be about 100% (w / v) distilled water. In one embodiment, methylrosaniline chloride can be used, which can be present at about 5% (w / v). In another embodiment, methylrosaniline chloride is not used.

[0097] EXAMPLE 5

[0098] In another embodiment, a topical formulation can be prepared, for example, sodium salicylate is selected as a chemical sclerosing agent, which is used at about 5% (w / v), and dextrose is selected as an osmotic sclerosing agent at 25% (w / v). Thus, the carrier can be about 100% (w / v) distilled water. In one embodiment, methylrosaniline chloride can be used, which can be present at about 5% (w / v). In another embodiment, methylrosaniline chloride is not used.

[0099] LITERATURE

[0100] Rodríguez Ramírez, Rafael; González Tuero, Jaime Humberto Alternative methods for the treatment of patients with infected wounds MEDISAN, vol. 15, no. 4, 2011, pp. 503-514 Provincial Medical Sciences Information Center of Camagüey, Santiago de Cuba, Cuba

[0101] Juárez-Arce V, Hernández-Pérez E. Sclerotherapy: a review of the topic. Dermatologia Rev. Mex, 1998; 42: 77-82.

[0102] Ocampo-Candiani J, Villareal-Rodríguez A, González-Madrazo R. Sclerotherapy. Dermatologia Rev. Mex. 1990; 34: 341-346

[0103] Moreno-González L. Sclerotherapy. Dermatology Rev. Mex1991;35: 245

[0104] Parsons, Margaret E. Sclerotherapy basics. Dermatol Clin 2004;22:501-50

[0105] Mediagrafic, Julio Enriquez Merino, Scleroterapia, el Línea, January-April 2008, http: / / www.mediqraphic.com / pdfs / derma / cd-2008 / cd081 c.pdf

[0106] Slideshare, Sergio Andrés Sánchez, Sclerosing Agents, online, November 24, 2017, https: / / www.slideshare.net / sesan90210 / aqentes-esclerosantes-2

[0107] Slideshare, Karina López Rojas, Sclerotherapy, online, October 2017, https: / / www.slideshare.net / klbienestar / presentacion-escleroterapia7next slideshow=1

[0108] Rubén Rivas Martínez, Effects of honey on wound healing, University of Valladolid, October 2017, httos: / / uvadoc.uva.es / bitstream / 10324 / 5594 / 1 / TFG-H93.odf

[0109] Rafael Rodríguez Ramírez, Jaime Humberto González Tuero, Alternative Methods for the Treatment of Patients with Infected Wounds, Santiago, Cuba, January 24, 2018, http: / / scielo.sld.cu / scielo.php?script=sc¡ arttext&pid=S1029-3019201 1000400015

Claims

CLAIMS. 1) Pharmaceutical composition of sclerosing agents characterized in that it comprises: a) A chemical sclerosing agent b) An osmotic sclerosing agent c) Methylrosaniline chloride. 2) The pharmaceutical composition according to claim (1) characterized in that it is contained in a pharmaceutically acceptable aqueous carrier. 3) The pharmaceutical composition according to claim (2) characterized in that the aqueous carrier may be any of the following: distilled water, double-distilled water, triple-distilled water, 4) Pharmaceutical composition for use according to claim (1) characterized in that the aqueous carrier may contain an agent in gel form. 5) Pharmaceutical composition for use according to claim (1) characterized in that it may contain one or more anesthetic agents. 6) The pharmaceutical composition according to claim (1) characterized in that the chemical sclerosing agent may be any of the following: chromated glycerin, sodium salicylate, iodine or a combination of two or more of these. 7) The pharmaceutical composition according to claim (1) characterized in that the osmotic sclerosing agent may be any of the following: hypertonic saline solution, hypertonic glucose, dextrose, sodium chloride, or a combination of two or more of these. 8) The pharmaceutical composition according to claim (6) characterized in that the glucose may be any of the following: sucrose, glucose, galactose, dextrose, maltose, fructose, mannose, lactose, trehalose, raffinose, acarbose, glycol, glycerol, erythritol, treitol, arabitol, ribitol, sorbitol, dulcitol, iditol, isomalt, malitol, lactitol, mannitol, xylitol, or a combination of two or more of these. 9) Pharmaceutical composition for use according to claim (1) further characterized in that the formulation is a solution for topical application. 10) Pharmaceutical composition for use according to claim (1) further characterized in that the concentration of the osmotic sclerosing agent is 0.01% to 50% weight / volume. 1 1 ) Pharmaceutical composition for use according to claim (1 ) further characterized in that the concentration of the chemical sclerosing agent is 0.01% to 30% weight / volume. 12) Pharmaceutical composition for use according to claim (1) further characterized in that the concentration of Methylrosaniline Chloride is 0.01% to 5% weight / volume. 13) Pharmaceutical composition for use according to claim (1) characterized in that the aqueous carrier may be from 50% to 100% weight / volume. 14) Use of the pharmaceutical composition according to claim (1) for the manufacture of a topical medicament for the treatment of injuries caused in the hypodermis, epidermis and dermis. Such as bruises, incised, puncture injuries, first, second and third degree burns, grade 1, 2 and 3 ulcers, varicose ulcers, arthritis ulcers, pressure ulcers, diabetic foot ulcers as well as in any cutaneous ecosystem. 15) Pharmaceutical composition according to claim (1) characterized in that it can be in an application medium. 16) Pharmaceutical composition according to claim (1) characterized in that it can be applied in alterations of the cutaneous ecosystem. 17) A process for the preparation of the pharmaceutical composition of claim (1) characterized in that it comprises the following steps: A) In a flask add 500 ml of distilled water and boil over low heat for 5 minutes. B) Add the selected osmotic sclerosing agent in small portions using a funnel and mix with slow, circular movements until it is completely incorporated and dissolved. C) Let the solution boil for 2 minutes, stirring continuously. D) Once the osmotic sclerosing agent has dissolved in the distilled water, the chemical sclerosing agent is added and mixed with slow circular movements until it is completely incorporated and dissolved. E) Let the solution boil for 2 minutes, stirring continuously. F) Once removed from the heat, it is poured into another flask using a funnel and filtered through a medium-pore paper filter. G) Once filtered, at room temperature add methylrosaniline chloride and mix with slow circular movements until it is completely incorporated and dissolved. H) Once at room temperature, it is poured into an amber bottle.