MX2010013030A - Pharmaceutical compositions containing melatonin for treatment of internal tissue and organ burns caused by corrosive substances. - Google Patents

Abstract

The present invention relates to a pharmaceutical composition and the method of manufacture thereof, wherein said composition serves to treat internal tissue and organ burns caused by corrosive substances, comprising pharmaceutically acceptable melatonin, polyethylene glycol, vehicles and excipients in the preparations. Ingestion of caustic substances is one of the most life-endangering accidents in the paediatric age group, requiring immediate handling and subsequent treatment of one of the most significant complications, for example alterations in the structure of the oesophagus. Melatonin reduces the oxidative response and the quantity of hydroxyproline in the late phase of oesophageal burning induced by sodium hydroxide.

Description

PHARMACEUTICAL COMPOSITIONS TO TREAT BURNT TISSUES AND INTERNAL ORGANS CAUSED BY SUSTA CORROSIVE TECHNICAL FIELD present invention has its technical field in the area citically in those pharmaceutical compositions that used xidants for the pharmacological treatment of tissue burns caused by the ingestion of corrosive substances. of the invention.- To develop a pharmaceutical composition, pediatric or adult captions, burns in tissues and orga- nized by corrosive substances.

BACKGROUND Elatonin was initially used for insomnia (regulation of the dians), Jet Lag syndrome (alterations of sleep by travel melatonin or pineal hormone, is generally known for its dular endocrine function and circadian regulation of the 24-hour cycle state. {Reiter, 1980), and has also been described as an eliminator of free radicals, substances that injure ular- (Reiter, 1995). In Vitro (study inside the laboratory), the m o a particularly effective debugger of the toxic hydroxyl radical the donation of an electron (Reiter, 1996, Tan, 1993). studies by Pieri, 1994, showed that the melurator of peroxyl radical is more efficient than vitamin E. Mela has been shown to stimulate glutathione peroxidase, an important agent at the mucosal level of the upper gastrointestinal tract. Barlow-tVa / den, 1995. As is known, ingestion causes lesions in the upper digestive tract (esophagus and these are considered chemical burns, either by a caustic) the latter is the most aggressive and is considered the lesion that are lesions of type colunctiva necrosis protunda and icosteroids of the Dexametazone and Prednisone type by space of an antibiotic type Penicillin or Ampicillin. Without two are producers of free radicals of oxygen and these aces to seriously injure the cell membranes and in causing them destruction. corrosive and caustic corrosion of the upper gastrointestinal tract or consequence of the development of a stenosis or perforation leads to significant morbidity and mortality. The products for ar contain alkalis, acids or detergents, each one of the cords histological and anatomical lesions, which cause damage to the upper rointestinal. The signs and symptoms after corrosive ing, are not reliable for clinical examination and the diag can be established after an esophagous endoscopy of medical and surgical instruments such as steroids, esophageal ations, placement of esophageal splints and reconstructions carried out for prevent esophageal stenosis but roversia in current management.

The free radicals derived from oxygen, in the acute lesion due to ethanoi, anti-inflammatories or ischemia, have been Melatonin and its metabolites act as eliminators of hydroxyl antioxyls, peroxium, singlet oxygen and peroxynitrite anion; also eliminators of superoxide anion radicals. Consists, it is reported that melatonin stimulates a variety of oxidants including: glutathione peroxidase (GPx), glutathione reduct sfato dehydrogenase. It has been found that melatonin and / or also inhibits the pro-oxidative enzyme, nitric oxide synthase. In ions which attenuate oxidative damage and prevent melatonin rigidity, it reduces the infiltration of polymorphonuclear cells and limits the adhesion of leukocytes to the endothelial cells, reducing blood flow and reducing edema.

DETAILED DESCRIPTION OF THE INVENTION characteristic details of this novel medicine for treatments and internal organs caused by corrosive substances amenté in the following description. e description of the figures.

The objective of this work was to examine the protective role of the early and late stage of esophageal burns and the administration of sodium hydroxide to rats. First it is stated that the digestive tract caused by corrosive substances are from hydroxyl radicals by the corrosives). In the study he s male Sprague Dawley, with average weight of 250-30Og, the nests of our bioterium. The rats were preserved at 27 ° C, under a light / dark cycle of 12hr / 12hr, ali standard diet for rodents and taking filtered water. The investigation approved the protocol and the animals were treated institutionally and federally. All procedures were either under general anesthesia, induced with dropertdol (2.5mg / kg, im) and mine (80mg / kg im). To prevent hypothermia, the animals had thermal mattresses and the abdominal skin was shaved and cleansed of the procedure, the esophagus was intubated with a catheter with a 0.86 mm i.d. (Intramedic, Parsippani, NJ, USA).

Later, a medial laparotomy was performed, the viscera were open to the left side and a segment of 1.5 cm. Of the patients subjected to the same surgical protocol but with the ad latonin at times equivalent to the MEL group (Group S + MEL). ma Chemical Co., St. Louis, MO USA), was dissolved in 0.5 ml of administered at 10 mg / kg in saline. The solution was normal saline solution. The melatonin, or the placebo, went through the dorsal vein of the penis, just after that for 6 hr. In the animals used for the evaluation of Hydroxy atonine, it was administered intraperitoneally every day for 14 days.

Generation of free radicals was evaluated in terms of lipidic oxidation (LPO) and glutathione peroxidase activity (GPx phenological were evaluated at 72 hr after the burn.A group were studied at: 0, 1, 6, 24,48 and 72 hr after esophageal stenosis was evaluated in five animals of each group of HP levels at the damaged site at 14 days of esophageal maturity.The measurement of the LPO products, malondia-hydroxyalkenes (4-HDA) allowed to establish their levels after the burn the esophageal segment 60 min at 4 ° C. The supernatant was diluted 1: 2 with 5 pmol / L clo 7.6). The samples were stored at -80 ° C. After refugation, a fraction of the supernatant (10μ? _), Proteins were taken (34). GPx was measured indirectly, in 50μ? _ Of the plow, by a coupling reaction with glutathione reductivity of the accumulated hydroperoxide: a spectrophotometric esophageal tissue system. This activity was referred to as m PH / min / mg oxidized protein (oxidized NADPH (μ?) Min / mg esophageal fragments of about 100 mg, dried at 1 showed constant weight, fragments were hydrolyzed ° C by 48 hr, filtered and evaporated until drying, the water content, neutralized to pH 7, and the different aliquots was determined by proline and HP using the Woessner method (expressed as micrograms of HP per milligram of tissue of the esophagus was dissected, cut, longitudinally opened experts (Pediatric Surgeons), in adura esophageal burns and lesions were classified according to the scale of 4 Baptist (5): 0 = no visible burn, 1 = first degree, grade erythema, non-bleeding ulcers and fibrin; 3 = third degree, ulcer data are presented ± the standard error of the mean (they were compared using the Student's test Neuman KeulsD tt normal test .. It was considered statistically significant when the calculations were made with Sigma Stat W, see 3.2 softw cago, IL1 USA). ultados. esophageal burns cause increase in LPO products (I baseline values of the NS group were 0.54 ± 0.03 pmol / mg, and post-burn durum, MDA and 4. HDA levels were high l / mg (p <0.05). addition, in the rats treated with melatonin, were high during the first hour post-burn (2.23 ± or the levels were consistently lower in all diadons compared to the group of NS.) In the rats that received f concentrations of LPO decreased during the first 24 hours, or similar to the Sham groups (Figure 1).

A significant increase in the activity of GPx was observed in the ales treated with melatonin after the burn (p <0.01) and the presence of edema in the deep layers, was infiltration of neutrophils and eosinophils. Comparison with the animals of the group involved the mucosa but not the submucosa: with infiltration gele- dade edema was moderate, HP levels in the group 68 pg / mg tissue (p <0.05 relative to the sham group and Mel groups). The levels of HP in the sham group and treated with Melatonin pg / mg tissue, respectively (Figure 3).

The procedure consists of preparing pharmaceutical forms that contain oral solution, 2.- intravenous injectable solution and 2a. intramuscular ctable, 3.- in capsules, 4.- in suppositories 5.- parch - in sublingual tablet, injectable grade melatonin solution covers the sterility, absence of pyrogens and drug toxicity for the dissolution of melatonin, consists of a melatonin in different proportions that integrate a solution q tonina in stable solution and under conditions specified by the elatonin in Oral Solution.

Concentration: 100 mg. for me.

Formula for 1 0O L No. Ingredients Quantity 1. - Melatonin 10.00 g.

"Tween 80" 75.00 g- 3.- Polyethylene glycol (400) 5.00 Kg. 4. - Acesulfame de potassium 500 5. - Sucrose 5.00 Kg. 6. - Essence chocolate flavor 500 ml. 7. - Mint flavor essence 500 ml. 8. - Sodium benzoate 250 gr- 9.- Purified water 4.5 L ielatonin is the active principle, it is added in a concentration to facilitate its dosage in children, in kilogram by weight, effective osis for the antioxidant action in the process of reversing serious uemadura in the esophagus. The purpose is to prolong the operation with the function of preservative and the proportion is from 0.1 to met in the formula the function of diluent and it is added for the purpose after dissolving the active principle and the components b! Is in water. The usage ratio is 1a! 10% odo to obtain melatonin in Oral Solution.

In a 450-liter stainless steel bowl, with mechanical stirrer 80", melatonin is incorporated, stirred for 20 minutes in a 3-liter stainless steel vessel, distilled and dissolved in acesulfame. This solution is dissolved in melatonin 3.- In a kettle with stirrer, distilled mec, and sucrose, stirring until dissolved and obtaining sucrose, add the benzoate, continue to dilute. Melatonin mixture 5.- With stirring to the melatonin solution of the 450 L container), the chocolate flavor essence and the peppermint essence 6.- Plowed Afo in the 450 L stainless steel tank with water p Fill the one hundred liters. sitting in an amber ampule of 5 ml. to be used in large-volume sterile logical dilution.

No. Inquirements Quantity 1. - Melatonin 10.00 kg.

C sodium treatment 40.00 gr- 3.- Citric acid 64.52 gr- 4.- Sodium bisulphite 10.00 gr. 5. - Polyethylene glycol (400) 75.00 L. 6. - Distilled water 14.89 L.

Nelatonin is the active principle, it is added in a concentration the purpose of facilitating its dosing in children, in kilogram considering the effective dose for the antioxidant action in the process of severe burn in the esophagus. The dose range n a range of 8 to 15% w / v. Sodium citrate and citric acid s Drmulation to prepare a pH regulator that helps to enter the active principle in solution. The concentration of speakers varies from 0.02% to 0.8% w / v. The sodium bisulfite in citric solution and then in the same container on the solution of sodium citrate and stir until dissolved. 3.- In a 1.0 L glass, it dissolves in 200 ml. of water the sodium bisulfite. 4 - S ion of melatonin the solution of citric acid, sodium citrate and sodium l-lt. 5.- The pH value is verified and adjusted according to either citric or sodium citrate to obtain a pH value of 7.0 to 7 distilled water. 7. ~ The solution is passed to an excellent filtering tank and filtered using a 0.22 micron micron dish.

The solution is packed in 5 ml amber glass ampoules. 9.- key to 1.5 Kg. Of pressure during 30 minutes.

Inspection is carried out to detect foreign particles, it is conditioned (pack and pack). recommended dose for corrosive injuries is 10 teadas in a scheme of 6 doses on the first day closest to the stión! Preferably corrosive immediately or in the first day of the second day would be a daily dose for 14 days. While fasting for his injuries, the medication will be admini venous and at the beginning of the oral route or gastrostomy generally 3.- Ethyl alcohol 37.5 L. 4 - . 4 - Propylene glycol 5.00 L. 5. - Distilled water 52.45 L.

Melatonin is the active principle, it is added in a concentration the purpose of facilitating its dosing in children, in kilogram considering the effective dose for the antioxidant action and blood concentration, after ovenosa, to help the process of reversing an effect of what the esophagus. Ethyl alcohol is used as a solvent in the concentration for this purpose, ranging from 25 to 4 to prepare. The propylene glycol is added to the common preparation; The recommended range is from 3 to 10%, in relation w / v. The caine is incorporated as an anesthetic and stabilizer in a range of elation to w / v. odo to obtain melatonin Injectable Intramuscular Solution n a stainless steel tank of 100 L. with recommended mechanical agitator is 10 mg / kg / dose, if the patient has co-oral and / or there are limitations of the intravenous route, you can muscle for as long as necessary. uptake of Melatonin. concentration: 100 mg. by infant suppository; 500 mg. in every s dultos. Formula for 100 kg. of suppositories for children.

No. Ingredients Quantity One 1. - Melatonin 6.666 kg. 2. - Colloidal silicate 1,333 Kg. 3. - Polyethylene glycol (300) 10.20 Kg. 4. - Polyethylene glycol (6000) 5.81 Kg. 5. - Polyethylene glycol (1540) 76.00 Kg. uía for 100 kg. of suppositories for adults.

No. Inqredientes Amount Und 1. - Melatonin 33.33 Kg. Ethylene glycols that are part of the mixture of components of the most important vehicle, fulfilling the function of diluent, bilizer. The required ratio is 20 to 90% w / v.

Obtaining Melatonin Suppositories.

In a stainless steel kettle, the polyethylene is added at a temperature of 90 ° C. until the dough is founded. 2 - tonina and the colloidal silicate. 3.- Add the powder mixture, stir 10 minutes. 4.- Empty to containers. 5.- It was left to. 6.- The container is sealed. 7.- The product is conditioned (it is rung). recommended dose is 10 mg / kg / dose, divided into 6 doses and 0 1 daily dose for 14 days.

Melatonin capsules. concentration: 100 mg. per capsule. Concentration: 250 mg. per order for 100 kg. of the preparation; 100 mg. per capsule. elatonin is the active principle, it is added in a mg concentration with the purpose of facilitating its dosage in children and after the discharge of the period of hospitalization, it is necessary to continue the administration to maintain a blood con tontin. Lactose is an ingredient whose function of the active ingredient to achieve a better distribution in filling the volume required to fill the container (capsule). The required ratio is 10 to 90% w / v. Stearate of rpora as a lubricant.

Obtaining the Melatonin Capsules.

Melatonin and lactose are mixed for 20 minutes in a "V" type s. 2.- Magnesium stearate and the components of the formula are added to the mixture for 1.0 min.

It takes the powder to the capsule filling machine for the li a of the powder adhered to the surface of the capsules. 5.- It is polished and conditioned (enblistan, encartona and packed). oral or gastrostomy the pediatric patient in ed No. Inqredientes Amount Unds. 1. - Melatonin 20,834 kg. 2. - Polyethylene glycol (6000) 0.084 Kg. 3. - Compressible sugar 62,500 Kg. 4. - Lactose 5.625 Kg. 5. - Croscarmellose sodium 1.041 Kg. 6. - Hydroxypropylcellulose 1,667 Kg. 7. - Polyvinyl pyrrolidone 1.667 Kg- 8.- "Tween 80" 0.834 Kg. 9. - Acesulfame of potassium 0.417 Kg. 10. - Chocolate powder flavor 0.625 Kg. 1 1 - Mint Flavor powder 0.625 Kg. 12. - Yellow Color No.5 0.834 Kg. 13 -. 13 - Magnesium Stearate 0.417 Kg. 14. - Ethyl alcohol of 96 ° 7,500 Kg. 15. - Purified water 7,500 L. uía for adults. 11. - Mint Flavor powder 0.625 Kg. 12. - Green color No.5 0.834 g. 13. - Magnesium Stearate 0.317 Kg. 14. - Ethyl alcohol of 96 ° 7,500 L. 15. - Purified water 7,500 L. elatonin is the active ingredient, polyethylene glycol is added as a solvent in a concentration, "xyropropylcellulose and croscarmellose sodium are incorporated into the solution of the active principle, the polyvinylpyrrolodone is binder and to help the disintegration of the tablet, the compressible car to improve the taste of the tablet, the presible lactos, are added to the formulation as diluents, stearate or lubricant.The proportions of the formula correspond to I mended. period for obtaining sublingual Melatonin Tablets.

In a kettle of stainless steel of 100 Kg. Of inilpirrolidone capacity, the mixture of the powders containing the granulation is moistened. 8.- The granulated powder is sieved in the oven for 3 hours at 50 ° C. 10.- The dry powder is sieved. The sieved powder is mixed with the magnesium stearate. 12.- S or in table-tennis machine. 13.- The packed and packed tablets are conditioned).

If the oral route or gastrostomy is used, the pediatric pediatric patient can take 100 mg tablets. of melatonin at kg / day to complete 14 days, (the dose limit should be 500 tablets of 250 mgr taking as a top dose 500 mg, complete 14 days of treatment.

Melatonin transdermal arches. concentration: 100 mg. By patch. Formula for 100 kg. of the pre No. Inquirements Quantity 1. - Melatonin 10.00 kg. 2. - Dimethyl sulfoxide 5.00 Kg. 3. - Polyethylene glycol (400) 20.00 Kg. Llo! Yn 21 E), Polymer butyl titanate and polypropylene sheet: riz is formed by dimethylsuiphoxide in a proportion of 1 to 20% co-solvent, the mixture polyethylene glycol, ethyl alcohol and propylene glycol 1 incorporated to the mixture in proportion of 20 to 80%, with entity. The "Pluronic F127" is added to stabilize the emulsion, learns in proportion of 2 to 30%. The carbopo! 940 is used lsionante and is incorporated in a range of 0.1 to 2%. The trietan nte pH regulator and it is recommended to use it in the range of 0.1 apply a transdermal patch immediately after daily and every hour for six doses until you have venous medicine, taking as a maximum dose 500 mg per dose (in four doses) to its weight). to obtain melatonin in transdermal patches.

In a stainless steel kettle with mechanical stirrer, polyethylene glycol 400, ethyl alcohol, propylene glycol and stir for three minutes, melatonin is added and stirred to dissolve.

Pharmaceutical compositions may be contained in: suitable acidity ranging from 5 ml. up to 150 mi. manufactured d and / or low density, polyethylene terephthalate, polyvinyl chloride, styrene, glass type I, II, III and IV, among others, with or without color. Thread, screw, cap to cap, child proof, made of polyethylene, polyethylene terephthalate, polyvinyl chloride, polypropylene, p n color. In a bubble pack of polyvinyl chloride (PVC) μ, which may or may not be coated with polyvinyl chloride (P 2 to 120 g / m 2 and adhered with aluminum foil or on cellophilic paper to treat burns in tissues and tissue). Corrosive substances provide the following benefits.

Severe lesions become moderate and moderate lesions are more effective than steroids because it acts by sweeping the radioenzymes (-OH).

The treatment can be applied immediately after exposure to free radicals prevents the progress of the burn. 4. Pharmaceutical compositions can be treated in the form of conditions that arise in the patient. 5.- Improve the efficiency. 6 - The treatment has few side effects and

Claims (1)

1. CLAIMS Having described my invention sufficiently, I consider it as, therefore, I claim as our exclusive property the following clauses: An oral solution to treat burns in tissues and organs caused by corrosive substances characterized by melatonin, "Tween 80", Polyethylene glycol (400), Acesulfame de pota flavor chocolate flavor, mint flavor essence, purified benzoate. to the oral solution of claim 1, characterized in that the m n an amount of 5.0 Kg, the "Tween 80" in 75 gr. the Polyethylene glycol; the Acesulfame of potassium in 5.0 Kg .; Sucrose in 5.0 K abor Chocolate in 500 ml .; mint flavor essence in 500 ml .; I hate in 250 gr. and purified water in 4.5 L A method for obtaining the oral solution of claims characterized in that it consists of the following steps: "" Heat 4.5 L. of distilled water and add 5.0 Kg. Of sucrose in jitar until dissolution until obtaining consistency of syrup. The sac ¾bor in the formula and once dissolved this one; Add to the syrup 250 gr. of sodium benzoate and continue to dissolve, Add the syrup to the melatonin mixture, (keep stirring to the melatonin solution, 5.0 kg of polyethylene glycol), 500 ml. of chocolate flavor essence and 500 ml. of essence s chocolate and mint act as flavorings for rganoléptica improvement. Flush the solution with purified water until completing 100 L. Identify the total solution per 1 .2 micron cartridge, Pack in bottles of 30 and / or 60 ml. of amber glass, Label flasks. The use of melatonin to make an oral solution to treat internal organs and ejidos caused by corrosive substances. Intravenous Injectable solution to treat burns in tissues caused by corrosive substances characterized by: Melatonin, Sodium citrate, Citric acid, Bisul, to the reactor, 10 kg of melatonin powder and shake during melatonin is the active principle. Gregar 5 L. of distilled water in a 10 L container. Then add citric acid and mix until dissolved. The citric acid is formulated to prepare a pH regulator that helps to concentrate the active principle in solution, diction to the mixture distilled water / citric acid, 40 gr. from citr gitar until dissolution. Sodium citrate also acts as a regul isolver 10 gr. of sodium bisulfite in 200 mj. of distilled water. hate works as an antioxidant, ezclar to the melatonin solution, the citric acid solution, the sodium bisulfite solution. Check the pH value of the total solution and adjust by adding sodium itrate to obtain a pH value of 7.0 to 7.3. Drill the solution with distilled water, roast the solution to a filtration tank and make a filtration capsule for microfiltration with 0.22 micron membrane. Pour the solution into 5 ml amber glass ampules. sterilize the solution in an autoclave at 1.5 Kg. pressure for 30 g .; Absolute ethyl alcohol, at 37.5 L; Propylene glycol distilled in 52.45 L. A method for preparing the Injectable solution intram claims 9 and 10 characterized in that it consists of the following i) Add 37.5 L. of absolute ethyl alcohol, in a mechanical stirring tank. This ingredient is used as Incorporate 5 Kg. Of melatonin powder and shake hard melatonin is the active ingredient, iii) Add 5 L. of propyl lidocaine base, in a 10 L container and shake has propylene glycol is used as a stabilizer and diluent and l incorporate as anesthetic, iv) Mix the solution of lidocaine / propylene glycol solution, and stir the mixture, to 10 minutes, v) Check the pH value of the solution and citric acid or sodium citrate to obtain a pH value d Fill the solution with distilled water, vii) Transfer the intramuscular solution to a filtration tank and filter the microfiltration capsule with 0.22 miera membrane in 3 ml amber glass ampoules. ix) Sterilizing in - The suppository for treating burns in internal tissues and organs by corrosive substances referred to in claim 13, wherein the formulation for children comprises: melatonin, which is in 6.66 g .; Colloidal silicate at 1,333 Kg .; Polyethylene glycol (300) and Polyethylene glycol (6000) in 5.81 Kg .; and Polyethylene glycol (1540) in 7 - suppository to treat burns in internal tissues and organs by corrosive substances referred to in claim 13, wherein the adult formulation comprises melatonin, which is 33.33 Kg .; Colloidal silicate at 1,333 Kg .; Polyethylene glycol (30 Polyethylene glycol (6000) in 5.81 kg, and Polyethylene glycol (540) in - A method for preparing the suppositories of the claim characterized in that it consists of the following steps: i) Add 10.20 Kg of polyethylene glycol (300), 5.81 Kg. of polyethylene 49.33 Kg. of polyethylene glycol (1540), in a kettle. Heat until it melts into a mass, ii) Mix in a melatonin container and 1,333 kg of colloidal silicate. The melatonin is the and the colloidal silicate is an ingredient whose function is dispersed of the active principle to achieve a better distribution in melatonin ma is in an amount of 14.14 Kg .; Lactose in magnesium stearate in 0.995 Kg. - A method for obtaining the capsules of claims 19, because it consists of the following steps: i) Mix 14.14 kg of melatonin and 84.865 kg of lactose minutes in a "V" type powder mixer. Active melatonin Lactose is an ingredient whose function is to dilute the active ingredient to achieve a better distribution in the volume mix required to fill the container, ii) Add to 0.995 kg of magnesium stearate and stir all of the formula by 1 min. The magnesium stearate is lubricant, iii) The powder is brought to the packing machine of c filling, iv) Clean the powder adhering the surface of the Condition capsules (enblistan, encartona and packaging). The use of melatonin to obtain capsules to treat internal tissues and organs caused by corrosive substances. Sublingual tablets to treat burns in tissues and organs caused by corrosive substances characterized by chocolate powder in 0.625 Kg .; Mint Flavor powder in 0.6 Yellow No.5 in 0.834 Kg .; Magnesium stearate in 0.417 ethyl 96 ° in 7.5 kg and purified water in 7.5 L. Sublingual tablets to treat burns in tissues and organs caused by corrosive substances referred to in the rei characterized because the formula for adults comprises: 39.682 Kg., Polyethylene glycol (4000) in 0.160 Kg .; Sugar 41 .483 Kg .; Lactose at 8.570 Kg .; Croscarmellose sodium and Hydroxypropylcellulose in 1269 Kg .; Pplivinylpyrrolidone in "Tween 80" in 0.634 Kg .; the Acesulfame of potassium in 0.625 chocolate powder in 0.625 Kg .; Mint Flavor powder in 0.6 green No.5 in 0.834 Kg .; Magnesium stearate in 0.317 ethyl 96 ° in 7.5 kg and purified water in 7.5 L. A method to obtain sublingual tablets to treat burn and internal organs caused by corrosive substances because it consists of the following steps: i) Melt 0.160 Kg of polyethylene glycol (4000), heating it to 100 minutes, in a kettle, ii) Incorporate Polyethylene glycol (40 complete the dissolution of polyvinylpyrrolidone, vii) Moisten the powders with the alcoholic solution of polyvinylpyrrolidone and melatonin to promote granulation, viii) Sifting the dust mesh No. 10. ix) Dry the powder in the oven for 3 hours at 50 dry powder per 16 ml. xi) Mix the sieved powder and magnesium powder, xii) Compress the powder in a tabl machine Condition sublingual tablets (packed, boxed The use of melatonin to make tablets sublinguale burns in tissues and internal organs caused corrosive p. Transdermal patches to treat burns in tissues and organs caused by corrosive substances characterized by melatonin, Dimethylsulfoxide, Polyethylene glycol (400), Car triethanolamine, Ethyl alcohol 96 °, Propylene glycol, Pluronic F 12 potassium and Purified water. Transdermal patches to treat burns in tissues and organs caused by corrosive substances referred to in the reivi characterized by the fact that melatonin is 10 Kg .; Dimetil Kg .; Polyethylene glycol (400) in 20 Kg .; the Carbopol (940) e ° 0. 200 Kg. Of potassium sorbate, then incorporate 0.5 K (940) and stir until dissolved lumps formed. Add triethanolamine and stir until obtaining a transparent gel, iii dissolution of melatonin 20 Kg. Of "Pluronic F 127" emulsify the mixture, iv) Add the gel or carbopol to the kettle and stir for 20 minutes to homogenize. the polypropylene laminate containers, vi) Seal the vii) Condition (pack and pack). The pharmaceutical compositions of claims 1, 2, 14, 15, 18, 19, 22, 23, 24 27 and 28 characterized in that the mammal. The pharmaceutical compositions of claims 1, 2, 14, 15, 18, 19, 22, 23, 24 27 and 28, characterized in that the an is a human (homo sapiens). The pharmaceutical compositions of claims 1, 2, 14, 15, 18, 19, 22, 23, 24 27 and 28, characterized in that the rat animates (Sprague Dawley).