WO2007102724A2

WO2007102724A2 - Effects of the photoelectrolysing property of melanines, analogues thereof and derivatives thereof on cell biology, and use thereof for various purposes

Info

Publication number: WO2007102724A2
Application number: PCT/MX2006/000016
Authority: WO
Inventors: Arturo SOLÍS HERRERA
Original assignee: Solis Herrera Arturo
Priority date: 2006-03-08
Filing date: 2006-03-08
Publication date: 2007-09-13

Description

Effects of the photoelectrolytic property of melanins, their analogues and their derivatives, on cell biology and their use with various ñnes.

DESCRIPTION

FIELD OF THE INVENTION

The sphere of technology or knowledge to which this invention applies is in the area that includes the study of energy processes in the area of Cellular Biology and its repercussions on the cell itself and the structures it forms, tissues, organs, systems , complete organisms, etc., that is: methods of obtaining and / or harnessing the radiant energy that emanates from the sun by uni or multicellular organisms, eukaryotes or prokaryotes, both in vivo and in vitro, in order to energize one or some of the multiple biochemical reactions that together make up the divine process that we know as life. We refer particularly to the so-called photoelectrochemical processes, through which living organisms, uni or multicellular, eukaryotes or prokaryotes, absorb energy from the electromagnetic spectrum that emanates from the sun and thereby obtain or generate hydrogen and oxygen atoms, mainly by means of the separation or partition of the water molecule, in addition to the generation of high energy electrons or in reverse, the generation of electron flow (electricity) resulting from the union of hydrogen and oxygen forming water, having application as a new method for the reduction of molecules of carbon dioxide, nitrates, and sulfates, both in vivo and in vitro. Because the reactions occur both ways, our observation also has application or repercussions for the generation of energy and / or electricity. BACKGROUND In Biology, living organisms obtain energy through different processes, but obtaining it from electromagnetic radiation (visible spectrum or light) has not been considered in living organisms, either single or multicellular except in the kingdom vegetable, and some algae, fungi and cyanobacteria, but in the animal kingdom only the usual metabolic pathways through which, through the degradation of the different molecules (lipids, protids, carbohydrates, cations and anions) that they enter the body through food, different types of energy are generated, the ATP being the universal currency of exchange. But until now, the possibility that organisms had the ability to significantly capture electromagnetic radiation and / or transform them into usable energy for the various processes necessary for life and / or for optimal development and function of the senses that allow us to interact with the environment. This property of dark or black compounds, generically referred to as melanins (mainly eumelanins and to a lesser extent pheomelanins) has gone unnoticed, but if we apply this new knowledge in the study of normal and pathological physiology of cells, tissues, organs and systems, a completely new panorama opens up and that allows to explain and / or understand more deeply some of the many mysteries of why the tenacious and / or persistent presence of melanins in the vast majority of living organisms. Melanins are described as substances whose function in the living organism has been focused or derived from the apparent protective function of UV radiation on the skin, but, in addition to the fact that it is now accepted that said compound is not as protective or impermeable for such radiations as previously thought, the presence of the pigment in internal and internal organs and structures remained an enigma, and worse, it was not granted the least importance. But the ability of melanins to absorb the visible spectrum in its entirety, and perhaps even more, in addition to using that energy to split the water molecule generating oxygen and hydrogen, allows us to begin to understand why the frequency of said pigment in areas very exposed to the sun, but it is not the purpose of absorbing radiation with a single protective purpose, but to use it productively, this is generating energy through hydrogen and generating oxygen, which is also very valuable for aerobic organisms. This greater availability of oxygen while the skin is darker, is proven by the fact that the darker the skin, the lower the concentration of hemoglobin in the blood, it is even described in the literature up to 20 grams per liter of difference between whites and blacks . Another fact in favor of the importance of the photolytic properties of melanins is the fact that the lungs are smaller while the skin is darker. And if we take into account this photolytic property of melanin, we can complement and begin to understand some mysteries such as the dynamics of aqueous humor, then the puzzle (synthesis, secretion, transport and excretion of aqueous humor) seems less complex, because if We accept for a moment, that melanins, are significantly involved in the secretion, transport and excretion of aqueous humor, we begin to form a more congruent scheme about why intraocular pressure is higher in the morning, since its secretion It decreases 45% during the night, which is understandable, since without light, the melanin that covers the ciliary body (tissue that produces such humor) decreases its energy efficiency for both secretion and excretion, because the lack of light in the night, results in a 45% decrease in the production of aqueous humor, as well as for excretion, since the energy that melanin allows t omar of light, also intervenes in the form significant in the processes of excretion (exit of the aqueous humor from the eye) of this liquid, since, at night, although the aqueous humor decreases almost half its production, the intraocular pressure rises gradually until, at dawn , it is characteristically the highest intraocular pressure of the day, and interestingly, as the day passes and the sun illuminates the pigmented tissues of the eye for hours, it is then that the intraocular pressure drops constantly until, at twilight, the intraocular pressure is the lowest of the day; although the production of aqueous humor increases, then; by 45% during the day, that is, during the lighting hours, but this increase in the production of aqueous humor possibly secondary to a greater amount of light and therefore of a greater amount of energy, is compensated in turn ; due to the greater efficiency of the mechanisms responsible for evacuating said liquid from the inside of the eye to the outside, thanks to the greater availability of energy in the form of hydrogen and oxygen, which is probably included in the metabolic processes by means of NADH and NADPH as well as of oxygen used for the multiple processes in which the latter intervenes, citing as an important example, the collection of electrons that are released from the metabolic pathway called oxidative phosphorylation, resulting from the catabolism of the different forms of reduced carbon that we ingest and which are our main source of energy, carbon that we exhale as carbon dioxide at the end of metabolic processes, which is the most oxidized form of carbon. This final compound

(CO ₂ ) that exhale or expel organisms is totally the opposite of vegetables, because

they absorb CO ₂ and water, and the light of the sun are carbohydrates (glucose) and

we absorb glucose and produce water and CO ₂ . This radical difference is one of the peculiarities that made us think, that the animal organisms were far from the vegetables, and therefore photosynthesis was only carried out by them (the vegetables) and we (the animals) in any way, because we do not have chlorophyll, and we were totally different from each other (vegetables and animals), but our discovery of the photolytic properties of melanins in the presence of water will come to revolutionize these concepts, which will significantly impact cell biology in general. Another example of the importance of the photolytic activity of melanins, we have when we study the process of light transduction, which occurs in part, in the photoreceptors of the mammalian retina and in part, coincidentally, in one of the more pigmented cells of the organism, and that is the pigmented epithelium of the retina, because in the texts that analyze this phenomenon (phototransduction) they cite a step in the biochemical process, of which its origin is unknown (according to the books) and that is the decrease in the intracellular pH of the pigmented epithelial cells as soon as they are illuminated, said decrease causes the chlorine channels to open, which leads to the rest of the events that result in the perception of light, if we accept that melanin meets the characteristics to be the mysterious "unknown" substance (Adler, 1998) that absorbs light and as a result increases the availability of hydrogen ions in the cytosol, without knowing the or They originate from these atoms, since there does not appear to be any other substance that degrades and releases this small element, but if we take into account that melanin only acts as a catalyst, and uses as water the water available in abundance in the medium in question, then the circle seems to be completed, since in addition, being a process that is energized through light, it does not spend ATP, which is also consistent with the metabolic processes described. Also this photolytic property of melanins, It explains why the concentration of oxygen in the blood that circulates in the most vascularized layer of the eye, called the choroid or uvea, is, at the entrance of 97% and at the exit of 94%, something unique in the whole organism, since the Carbon dioxide concentration if it is the same as in the rest of the economy and is 40% on the venous side. And according to the literature, carbon dioxide stimulates the process of water photolysis, but it is not known if it is through stimulating melanocyte or melanin itself. For a detailed description of how in vitro melanins capture electromagnetic radiation and generate hydrogen and oxygen from water, as well as the opposite, that is to say they bind hydrogen and oxygen producing water and generating electricity, we refer the reader to the GT patent application / a / 2005/00006.

Photosynthetic microbes such as green algae and cyanobacteria, which extract hydrogen from water as part of their metabolic activities using light energy as the main source. But as oxygen is produced together with hydrogen, it is the oxygen sensitivity of these enzyme systems that possibly limits the hatching of these microorganisms. In addition, the production of hydrogen from photosynthetic organisms is too low to be biologically viable.

The natural material that also part or separates the water molecule, but in vegetables and algae and that has been very studied is chlorophyll, but because its affinity for light falls between 400 nm and around 700 nm, the The rest of the light energy is lost, so it is estimated that 80% of the energy used is wasted, unlike melanins, in which the absorption of electromagnetic radiation comprises the entire visible spectrum and perhaps a little more, amen that seems to also absorb kinetic energy. The above is possible in the area of biology, as it was expected that the Nature takes advantage of all forms of energizing in one way or another all the biochemical reactions that give rise to or continuity of life. Until now, the ability of uni or multicellular non-vegetal organisms to take advantage of the radiant energy of the electromagnetic spectrum had not been detected or described, in order to energize one or more of the multiple reactions that occur in organisms in the animal kingdom. These were the reasons why we decided to report and patent any use derived from the knowledge of the property of melanins as an electrolysing element of water, because of its affinity for the electromagnetic spectrum that goes from 200 to 900 nm at least and maybe more, and due to the physiological characteristics of the tissues in which said pigment is normally found, where parameters such as tissue, arterial, capillary and venous oxygen concentrations are striking, it is why we decided to register or patent any derived use from the fact that by illuminating melanin or melanins, we would obtain the photolysis of the water molecule generating hydrogen and oxygen atoms, in addition to other products such as OH, hydrogen peroxide, superoxide anion, and high energy electrons, as well as the melanins' ability to sustain and catalyze the inverse reaction, that is, to bind the hydrogen and oxygen atoms or forming water molecules, also generating electricity. Any use or direct or indirect use of this property of melanins or progress in the study, description, manipulation and application in a multitude of processes in all fields of knowledge (biological, biochemical, physical, physicochemical, etc.) opens a door for us. of unsuspected scopes, and because it was not previously known that apart from plant chlorophyll, and cyanobacterial pigments, other living things in the animal kingdom could capture solar energy in some way or another, in this case, We patent any use or utility of knowledge derived from the fact that nature uses melanins to generate energy through the photolysis of water and uses it (energy) for the development, impulse or optimization of some or some of the multiple cellular biochemical processes. Definitions: In the description and reinvindications of the invention, the terminology used is in accordance with the following definitions:

For the purposes of this patent, when we write melanins, we refer to melanins, melanin precursors, melanin derivatives, variants and analogs of melanins (polyMdroxyindole, eumelanin, pheomelanin, allomelanin, neuromelanin, humic acid, fulerenes, graphite, polyindolquinones, acetylene black (acetylene-black), pyrrole-black (pyrrole-black), indole-black (indole-black), benzene-black (benzene black), thiophene black (thiophene-black), aniline-black (aniline-black ), hydrated polyquinones, sepiomelanins, black dopa (dopa-black), black dopamine (dopamine-black), black adrenaline (adrenaline-black), black catechol (catechol-black), 4aminocatecolnegra (4 amine catechol-black), (simple linear chain, aliphatic or aromatic.) or its precursors such as phenols, aminophenols, or diphenols, indole-polyphenols, cyclodopa, DHI and DHICA, quinones, semiquinones or hydroquinones, L-tyrosine, L-dopamine, ortho benzoquinone morpholino , dimorpholino-ortho-benzoquinone, morpholincatech, orthobenzoquinone, porphirin-black, pterin-black, ommochrome-black, nitrogen-free precursors, any of the above-mentioned with any particle size (from 1 angstrom to 3 or 4 cm), all the compounds mentioned above, electroactive, in suspension, in solution, in gel, in the cytoplasm, in modified liposomes, which absorb ultrasound in the range of a MHz, natural or synthetic, of plant, animal or mineral origin; pure or mixed with organic or inorganic compounds, ions, metals (gadolinium, iron, aluminum, gold, silver, nickel, copper, erbium, europium, praseodymium, dysprosium, holmium, chromium or manganese, lead selenide, titanium, various alloys and special, that is to say any metal or compound known or unknown to date; etc). Gadolinium is a very effective metal. The metal is incorporated into the melanins in ionic form or as a particle both in vivo and in vitro, in addition to drugs or drugs, energizing the photoelectrochemical design with electromagnetic radiation, light (natural or synthetic, coherent or not, monochromatic or polychromatic) with Wavelength mainly between 200 and 900 nanometers, although other wavelengths and other types of energy, for example kinetics, are also effective although in varying degrees, according to the rest of the conditions (pH, temperature, pressure; combination, doping ; etc).

Photolysis: refers to the partition of the water molecule into hydrogen and oxygen, a process that is energized, in the case of melanins through the absorption of the visible spectrum of electromagnetic radiation.

Dynamics of aqueous humor: refers to the synthesis, circulation and excretion of aqueous humor in the eye.

Glaucomatous optic neuropathy: a mysterious disease, which constitutes one of the first three causes of blindness in the world, being more frequent and severe while the skin is darker and consisting of an atrophy of the optic nerve, which may or may not increase with intraocular pressure

Energy: defined as the ability to do or perform a job. Energy can take several forms: mechanical, thermal, chemical, etc. Age-related macular degeneration: It is the first cause of blindness in Caucasian countries, and it consists of the gradual disappearance of structures in the macular region such as vessels, melanocytes, photoreceptors or sometimes an angiogenesis response is awakened. due to the prevailing hypoxia, which may be secondary to the decrease in melanocytes, melanin and blood vessels in the area.

Diabetic retinopathy: It is the first cause of blindness in the population that goes from 18 to 65 years. Its physiopathogenesis is not fully known, but hyperglycemia seems to be the initial basis of the problem, since it has been shown that at the week of increasing blood glucose, changes in the eye begin, for example vasodilation, which It can be explained by an increase in the oxidative phosphorylation substrates, which results in a greater demand for oxygen, that is, a relative hypoxia develops, which the body compensates with vasodilation.

DETAILED DESCRIPTION OF THE INVENTION The invention includes, essentially in describing and therefore making known, the important effects that have on cell biology, the fact, so far unnoticed that at room temperature and using natural or artificial light as the only source of energy, melanins, both in vivo and in vitro, have the property of splitting the water molecule, obtaining hydrogen and oxygen atoms, as well as high-energy electrons and also, in turn, can achieve the opposite event: unite hydrogen and oxygen atoms obtaining water and electric current, for the above, nature uses melanins as the main or central electrolysing material, these reactions that occur intra or extracellular, even in vitro, can occur to a greater or lesser degree low a myriad of physical or chemical stimuli, internal or external. That is, the effects of melanins are so important for nature, that cells begin to increase their synthetic activity of this molecule when any intra or extracellular reaction begins to occur more or less repetitively. Inside the eukaryotic cell, specifically the melanocyte; The main material, the indispensable solute for the photoelectrochemical principle to work, is melanin in a soluble state, given the remarkable ability of melanins to capture photons of wavelengths between 200 and 900 nm of the electromagnetic spectrum, mainly but not only in that region of the spectrum; since the pigment is sensitive to almost the entire electromagnetic spectrum, which is probably effected by the peripheral portions of the molecule, both in vivo and in vitro; which is followed by the generation of high energy electrons, from low energy electrons. These high-energy electrons are directed towards the free radical centers of the compound, where they are probably captured by some element, for example any metal such as iron, copper, or other, from which they are transferred to a primary electron acceptor, of an uncertain nature. to date, since the binding is complex and they comprise ionic interactions, also depending on the pH. This electron transfer releases energy, which is used to establish a proton gradient. The combination of melanin molecules and water forms what can be called a photosystem, which absorbs light energy using it for at least two interrelated activities: remove electrons from water and generate a proton gradient. The components of melanin are in very close contact with each other, which facilitates the rapid transfer of energy. At 3 picoseconds of being illuminated the Melanin reaction centers respond by transferring a photoexcited electron to the primary electron acceptor. This electron transfer generates a positively charged donor and a negatively charged acceptor. The importance of the formation of two oppositely charged species becomes apparent when we consider the reduced oxide capacities of these two species, since one of them is deficient in electrons and can accept electrons, which makes it an oxidizing agent. In contrast, the other compound has an extra electron that can easily be lost, making it a reducing agent. This event - the formation of an oxidizing agent and a reducing agent from light - takes less than a billionth of a second and is the first essential step in the photolysis of water.

Because they are charged the opposite way, these compounds exhibit an obvious attraction between them. The separation of charges is stabilized (probably) by their movement, on opposite sides of the molecule; the negative compound being the one that first gives its electron to a quinone (Ql), and possibly then the electron is transferred to a second type of quinone (Q2), which produces a semi-reduced form of the quinone molecule, which may be strongly linked to the reaction center of the melanin molecule. With each transfer, the electron is getting closer and closer to the reaction center of the melanin molecule. The portion of the positively charged melanin is reduced, which prepares the reaction center for the absorption of another photon. The absorption of a second photon sends a second electron, along the path (negatively charged melanin to the first and second quinone molecule -Ql and Q2-), this second molecule absorbs two electrons, so it is combined with two protons The protons used in this reaction could derive from the melanin molecule itself or from the surrounding water, causing a decrease in the concentration of hydrogen ions in the photosystem, which contributes to the formation of a proton gradient. Theoretically, the reduced quinone molecule dissociates from the melanin reaction center, being replaced by a new quinone molecule. These reactions occur at room temperature, but modifying, for example temperature, reactions in one way or another can be favored, depending on the control of the rest of the variables: pH, magnetic fields, movement, solute and solvent concentrations, amount of electromagnetic radiation, their nature, purity of melanin, whether it is doped or not, partial pressures of gases, shape, etc.) and of the main purpose that the process is to be given given the type of cell, tissue or amount of water present or available. In the presence of metals or Boron, Hydrogen works with -1.

The separation of the water molecule into hydrogen and oxygen atoms is a highly endergonic reaction due to the stable association of hydrogen and oxygen atoms.

The separation of the water molecule (in hydrogen and oxygen atoms) in the laboratory requires the use of a strong electric current or to raise the temperature almost to 2000 ° C. The above (electrolysis or photolysis of water) is achieved by melanin, both in vivo and in vitro; at room temperature using only the energy it obtains from light, principally but not exclusively between 200 and 900 nanometers of wavelength, whether from a natural or artificial source, coherent or not, concentrated or dispersed, mono or polychromatic. It is estimated that the redox potential of the oxidized form of quinone is approximately +1.1 V, which is strong enough to attract the tightly bound electrons of low energy of the water molecule (redox potential of +0.82), which separates the molecule into hydrogen and oxygen atoms. The separation of the water molecule by photopigments is called photolysis. The formation of an oxygen molecule during photolysis is thought to require the simultaneous loss of four electrons from two water molecules according to the reaction:

2H ₂ O → 4H ⁺ + O ₂ + 4e ~

A reaction center can only generate a positive charge or its oxidizing equivalent at a time. This problem is hypothetically solved by the presence of 4 nitrogen atoms, in the reaction center of the melanin molecule, each of which transfers a single electron. This concentration of nitrogen, perhaps accumulates four positive charges by transferring four electrons (one at a time) to the nearest quinone molecule. The transfer of electrons from the nitrogens of the reaction centers to quinone ⁺ is achieved by passing through a positively charged tyrosine residue. After each electron is transferred to quinone ⁺ regenerating quinone, the pigment is reoxidized (again to quinone *) after the absorption of another photon into the photosystem. Thus, the accumulation of four positive charges, (oxidizing equivalents) by the nitrogen atoms of the reaction center, is modified by the successive absorption of four photons by the melanin photosystem. Once all four charges have accumulated, the quinone oxygen-releasing complex is able to catalyze the removal of 4e ^~ 2EbO, forming an O ₂ molecule, and regenerating the completely reduced accumulation of nitrogen from the reaction center. The protons produced in the photolysis are released in the middle, where they contribute to the proton gradient. The photosystem must be illuminated several times before a release of O ₂ and therefore hydrogen that is capable of being measured occurs, indicating that the effect of individual photoreactions must accumulate before O2 and hydrogen are released.

Quinones are considered mobile electron carriers. Let us not forget that all electron transfers are exergonic and occur as electrons are successively transferred to carriers with an increasing affinity for electrons, (more positive redox potentials) The need for the presence of mobile electron carriers is manifest. The electrons generated by the photolysis can pass to several inorganic acceptors, which are therefore reduced. These electron pathways can lead (depending on the composition of the mixture used) to the eventual reduction of nitrate molecules (NO ₃ ^" ) in ammonia molecules (NH ₃ ) or sulfates in sulphydryls (SFT), reactions that convert waste inorganic compounds necessary for life, so the energy of sunlight can be used not only to reduce the most oxidized form of carbon atoms (CO ₂ ) but also to reduce the most oxidized forms of nitrogen and sulfur, which both in vivo and in vitro, with obvious advantages, the above was cited a little more extensively and more focused on the in vitro aspect in patent application GT / a / 2005/00006.

The production of an O2 molecule requires the removal of four electrons from two water molecules, the removal of four electrons from the water requires the absorption of four photons, one for each electron. On the other hand, there is also evidence that the Melanin also captures kinetic energy by converting it into manageable energy for the cell, such as hydrogen and oxygen or vice versa, water and electricity. The particular composition of the cell membrane and the cytosol are important parameters for obtaining the products of the reaction in particular, since the presence of electrolytes both in vivo and in vitro, their nature, the use of magnetic fields , the use of kinetic energy apart from electromagnetic radiation; the addition of various compounds - doping - (organic and inorganic, ions, metals, drugs or drugs) to the photosystem that initially is only melanin and water, plus the addition of electrolytes, plus the addition of drugs, as well as temperature management , the control of the partial pressures of the gases, the management of the generated electric current, the application of magnetic fields, the pH level, makes the final destination is to recover electrons, or protons or oxygen, as well as resulting compounds according to the formulation of the medium in which the melanin is dissolved. Thus, the heart of any effective photoelectrochemical design is melanin both in vivo and in vitro. Electron transfer releases energy, which is used to establish a proton gradient.

The movement of protons during electron transport can be compensated by the movement of other ions present in the intra or extracellular medium. The electrolysing properties of melanin (among many others) in vivo; they can explain the peak generated by light, an observable phenomenon in the electroretinogram, since when the melanin illuminates, the intracellular pH lowers, which activates the pH sensitive chlorine channels in the basolateral cell membrane. (The peak of light is an increase in the potential that follows the FOT (fast oscillation through) phase and forms the slowest and longest direct current electroretinogram component (Kris 1958, Kolder 1959,

Kikadawa 1968, Steinberg 1982.) They also intervene in the dynamics of aqueous humor, because they explain in a consistent way why intraocular pressure decreases during the day, although also during the day the production of aqueous humor increases by 45%, both processes during the presence of light, and at night the formation of aqueous humor decreases by 45% and increases the intraocular pressure by 40%, so it is observed that light energizes significantly, crucial processes of the dynamics of aqueous humor , which can be supported by the observation that drugs that stimulate melanocytes (beta blockers) are not effective overnight. Melanins, precursors of melanins, derivatives of melanins, variants and analogs of melanins; They remove electrons from water and generate a proton gradient.

Light-dependent reactions can also provide energy to reduce CO ₂ to CH ₂ O, nitrates to ammonia and sulfates to sulphydryls both in vivo and in vitro. Melanin absorbs all electromagnetic radiation, including soft and hard ultraviolet, the entire visible spectrum and near and far infrared lengths. (Spicer & Goldberg 1996). It is not remote that it can absorb other types of energy such as kinetics or other wavelengths far from the electromagnetic spectrum. It is also interesting to consider the use of the photoelectrochemical properties of melanins, in industrial processes based on biological systems, for example the generation of hydrogen and oxygen or the alternating generation of electrical energy. EXAMPLES The following examples are based on photoelectrochemical activity, which can be directly or indirectly affected in melanins, present in biological systems, in order to claim pharmaceutical compositions for prophylaxis or therapy. The affectation of the photoelectrochemical properties can favor some of the reactions of: photolysis or photosynthesis of water that were explained.

Example 1. - For the eye, the most important products apparently are oxygen and hydrogen, and therefore, the physiology of the eye tends to destabilize the reaction, biasing it towards obtaining said elements. We can have the test by observing the concentrations of oxygen in the arterial blood that enters the eye, which are 97%, and in the venous blood they are 94%, the CO2 concentration being 40%. The circulation time is estimated at 5 seconds. It is accepted that photoreceptors are the tissue that spends more oxygen and therefore energy of the whole organism, that is; 10 times more than the cerebral cortex, six times more than the coronary, and 3 times more than the renal cortex. The greater the activity of the melanocyte and / or the greater the amount and melanin, the greater the substrate for photolysis.

Example 2: Nature takes advantage of everything within its reach, and that explains the presence of melanin in any living being that is exposed to electromagnetic radiation, since it is accepted that in itself, melanins do not act as simple sunscreens, something like that as a 2% zinc sulfate solution, but it is something extraordinarily more complex, since nature absorbs light energy through melanin and transforms it into energy that can be used for the organism in question. Example 3.- In the case of the eye, nature shows us the example of absorption and use of light, perhaps maximum, since the concentration of melanin and water is the highest in the body (40% more melanin than in the skin, and 97% of the volume of the eye is water). That is, the two essential elements for the generation of oxygen and hydrogen from water (photolysis) to happen, are available in high concentrations and all the time.

Considering examples 1, 2, 3, I claim the pharmaceutical compositions, which are used in a therapeutic or preventive way for the treatment of ocular diseases that present with hypoxia and blood deficit, for example choroidosis, optic neuropathy, ischemic ocular syndrome, carotid insufficiency, and others.

Example 4.- According to example 3, nature not only provided the eye of both elements (melanin and water) in relative abundance, but also concentrated the light through powerful lenses the cornea and the lens, the latter with a power in the 150 diopters air. That is, in the eye we have a clear example that nature knows about photolysis since the beginning of time, and designed and developed a genetic code capable of concentrating the three necessary elements in a single organ, whose weight ranges around seven and half grams

Example 5.- Because the photolysis reaction takes 3 picoseconds, the amount of oxygen and therefore hydrogen generated in the pigmented tissues of the eye is such that in order to be evacuating said gases or elements by means of hemoglobin of the blood, the eye has the highest amount of blood per minute compared to any other organ in the body, to cite an example: the blood flow of the brain is 0.5 mL X gram of tissue X minute, and in the eye it is 15 mL X gram of tissue X minute. This explains why nature took the job of providing the eye with the first intracranial branch of the internal carotid: the ophthalmic artery, a vessel with a blood flow greater than the renal artery.

Example 6: Due to the concentration of light, the eye tends to increase its temperature and the prodigious circulation of the eye apart from its multiple and even unknown biological functions, also serves to cool the tissue, due to the affinity of hemoglobin for infrared radiation

Example 7.- Electromagnetic radiation activates melanocyte, and this results in a greater bioavailability of melanin and other compounds that generate pigmented cells. When we activate the melanocytes in sufficient time and form, either by physical or chemical methods (with pharmaceutical compounds, for example) the retina can enter a metabolic state resistant to ischemia, a fact that can be used for therapeutic or prophylactic purposes in diseases such as diabetic retinopathy, age-related macular degeneration, glaucomatous optic neuropathy; carotid insufficiency and others.

Therefore, I claim the pharmaceutical compositions, which are used in therapeutic or prophylactic way to treat diabetic retinopathy, or age-related macular degeneration, in any of its varieties (dry or wet) Example 8.- In support of the previous example , we will cite 5 facts described in the literature, which happen when activating melanocytes, and that in one way or another contribute to this interesting state resistant to retinal hypoxia, which on the other hand, may not be exclusive to this tissue, but It is the example we handle. These events are 1.- By increasing the amount of melanin, the bioavailability of oxygen and energy increases (hydrogen) obtained from water photolysis. 2.- Melanin forms covalent bonds with thiols, that is, that proangiogenic factors such as TGF, and VEGF or others, which contain cistern, are linked and therefore pharmacologically inactivated by melanin. 3.- Angiogenesis requires some degree of inflammation, however minimal, and especially in the early stages, and melanin captures interleukins and prostaglandins, so it is a natural anti-inflammatory, 4.- The secret melanocyte "Pigment epithelium derived factor "PEDF (Dawson 1999), which is described as one of the compounds with the highest known anti-angiogenic activity. 5.- Melanin is a compound that contributes significantly to the stability of a cell or tissue, for example because it is a natural buffer, it also acts as an electron donor and acceptor, on the other hand it chelates and inactivates potentially harmful substances for the tissue, reducing the amount and activity of the same, also, as it also preserves substances that positively affect the biology of the tissue, it seems to function as a store that discharges said substances slowly and prolongedly. Example 9.- The activation of the pigmented elements of the eye can be achieved by substances that prevent the pituitary inhibitory effect on the pituitary intermediate pars, because the secretion of alpha MSH is tonic, and decreases when the hypothalamus, through the secretion of dopamine (or other neurointermediary) which significantly inhibits or decreases the secretion of said melanocyte stimulating hormone.

Example 10.- Melanocytes have some known and other unknown and even unsuspected effects, we will cite for example, the effect that melanocytic activity has on corneal morphology, because when we inhibit melanocytes by means chemicals (with pharmaceutical compounds, for example) the cornea tends to vascularize significantly, but when we eliminate them completely, a non-inflammatory ectasia appears, something similar to keratoconus, an effect that could be completely prevented by the topical instillation of 10 microliters of a 10% melanin solution. Example 11.- Pharmacological or other manipulation of melanocytes and therefore the amount of melanin, or the application of melanin itself, in solution for example; It can have a significant beneficial effect on the evolution of diseases of the anterior segment that present with neovascularization (pterygiums, chronic ulcers, persistent inflammations, degenerations, dystrophies, etc.), or that occur with ectasias such as pronounced or irregular astigmatisms, including keratoconus.

Considering examples 10 and 11, claim, pharmaceutical compositions, to treat therapeutically or prophylactically non-inflammatory corneal ectasias and / or some other degenerations that can be improved by modifying the activity of melanocytes and / or melanins Example 12.- There are corneal dystrophies that mainly or mainly affect Caucasians, which makes the hypothesis of a lower activity of melanin consistent, which can be considered as a possible indication of melanin used topically, or activators of melanocytes. Example 13.- The secretion of alpha MH secreted by the intermediate pituitary gland is higher while the skin is whiter, which in the end results in a higher incidence of pigmented tumors (melanomas) for example in the choroid. So an intermediate pars inhibitor (dopamine for example) could be a prophylactic treatment against the development of pigmented tumors of the choroid (or other parts of the body). Example 14.- The ability to combine melanin is prodigious, if we take into account its molecular weight, which is estimated in millions of daltons. Therefore, it is a natural detoxifier, since substances, growth factors, metals, organic compounds, inorganic compounds, or others, of plant, animal, etc., that daily penetrate or attempt to do so to the organism, are captured, bound and inactivated by melanin, and this is subsequently desquamated by the skin and hair, which leads to said factors, xenobiotics or potentially harmful compounds being returned abroad, hence the activation by means of pharmaceutical compositions of melanocytes is a Therapeutic way to treat chronic poisonings, for example iron, a problem for which, the desquamation of melanin, seems to be the only method available to the body to eliminate or combat it. Example 15.- The anti-angiogenic properties of melanins, partially explained in example 8, can give us the guideline for the treatment of systemic arterial hypertension, since the anti-angiogenic effects of melanins are permanent and tend to increase with age, until 50 years, and then the melanins tend to disappear, so, to treat or prevent primary systemic arterial hypertension, whose etiology may be due or significantly influenced by the accelerated disappearance of the body's capillaries (Duane 2004), a possible treatment is the inhibition by means of pharmaceutical compositions of the activity of melanocytes, which would decrease the activity of one of the main factors in the gradual disappearance of the capillaries of the economy.

Therefore, I claim, pharmaceutical compositions, for the prevention or treatment of diseases that occur with an accelerated disappearance of blood vessels, such as they are idiopathic systemic arterial hypertension, peripheral vascular insufficiency, and similar ones.

Example 16.- According to example 15, the melanin / melanocyte dupla tends to antagonize vascular endothelial cells, so, in the case of glaucomatous optic neuropathy, inhibiting or antagonizing melanocytes, favors the permanence of the vascular channels, that is, the irrigation of the optic nerve head can remain in a better anatomical as well as functional state. Other important vessels that also tend to disappear with age or due to diseases (diabetes mellitus, atherosclerosis, systemic arterial hypertension and others) are vorticose veins, which leads to a significant increase in intraocular pressure, and in these cases, inhibiting Melanocytes are also beneficial because we decrease their antiangiogenic activity. And finally, also in relation to glaucomatous optic neuropathy, we have the aqueous veins, episcleral location, or the collecting channels or the Schlemm canal, all of them formed by vascular endothelial cells, which naturally tend to disappear over time , which is accelerated by the antiangiogenic activity of the melanocytes, and the disappearance of these structures, whereby 80% of the aqueous humor in the human drains drains or leads to an increase in intraocular pressure, which can be treated or prevented by inhibiting melanocyte by means of pharmaceutical compositions. It is no accident that the first drug available for the treatment of glaucoma, pilocarpine, used for this purpose since 1860, is a melanocyte inhibitor. Example 17.- When we measured the electrical changes of melanin, in vitro, by means of an oscilloscope, the variations in voltage were up to 4 V, which transpolated to pH units means approximately 12. (Each unit equals 58 mV in alive approx. Kart 2002.); We consider it significant because melanins have a buffering property per se, so the change must be greater, but it is masked by the intrinsic buffer property of melanin, so we only detect a part of this pH modification, a pH change whose magnitude is in accordance with a biological system, because if it were greater, it would probably destroy or significantly injure the cell, but a change of that magnitude is sufficient to induce the biological changes in which this extraordinary compound intervenes.

Example 18.- In order to measure the biological importance of a decrease in blood pH from 0.2 to 0.12 pH units, we will mention that said decrease increases Calcium concentration by more than 10%, in the case of blood. In addition, the pH of the whole blood ranges from 7.38 to 7.44, the arterial blood ranges from 7.36 to 7.41 and that of the venous blood ranges from 7.37 to 7.45, that is, the variations are within a very narrow range, so the Difference of 2 tenths of pH unit is really significant in a biological system. Example 19.- The images of the production of electrical energy by means of melanin, in an oscilloscope, allow us to visualize that the melanin molecules work randomly, so there is also potentiation and cancellation of electron emissions and hydrogen and oxygen. Example 20.-, Melanocyte is the cell with the highest affinity for calcium in the organism, since it is a thousand times more similar to calcium than bone, since although the latter has a greater amount, said cell only deposits it in mineral form. Therefore, the stimulation of melanocytes by physical or chemical methods (for example, pharmaceutical compositions) will probably positively modify the bioavailability of calcium. Example 21.- The blood that enters the eye follows two paths, one is through the retina and another is through the choroid or uvea. Retinal vessels do not have pigment, nor have pigment cells been described near them or envelop them, and oxygen saturation

on the arterial side it is 91% and on the venous side it is 60% with a saturation of CO ₂

of 40%. And the choroidal vessels, which are wrapped by a significant amount of melanocytes, have different figures, since oxygen saturation is 97% in the

arterial side and 94% on the venous side, with a CO ₂ saturation of 40%. The

Photolytic properties of melanins can explain this intriguing difference. So it is very likely that the stimulation of choroidal melanocytes improves the bioavailability of oxygen from the surrounding tissue, which, remember, the distance that an oxygen atom can effectively travel from the point of view of usefulness for metabolic effects, is limited to 100 microns

Example 22.- Another biological event or event that supports our patent is the case that by illuminating the cells of the retinal pigment epithelium, normally; there is a decrease in the values of intracellular pH, a change that in the literature consulted to date and of recent publication is not explained, only a substance is identified that has not been identified until such time as it could be responsible, but if we take into account The property or photoelectrolyzer of melanin is then explained, since melanin acts as a catalyst, so it is not modified during the process, and the substrate it uses, which is water, is sufficiently available in the surrounding environment ( in the eye) in addition to the fact that, as it is a reaction that is energized by means of light, then it does not spend ATP, which is very consistent with the rest of the phenomena described in phototransduction, Summarizing, in the presence of light or electromagnetic radiation, melanin breaks the water molecule and generates hydrogen and oxygen atoms or vice versa, which then explains the two events mentioned above, that is: the mysterious saturation of 94% oxygen of the choroidal venous blood (the choroid is very pigmented normally) and the decrease in the cytoplasmic pH of the pigmented epithelial cells of the retina when they are illuminated. For something nature put so much pigment in the eye, 40% more than in the skin. Therefore, I claim, pharmaceutical compositions, to improve the events or phenomena of phototransduction or diseases that occur with the same condition as pigmented retinosis, toxic retinopathy by xenobiotics, etc. Example 23.- Another example that supports our patent it is the peak generated by observable light in the electroretinogram or recording of the electrical activity of the retina, pigmented epithelium and choroid; Since, when the melanin is illuminated and hydrogen atoms are generated, the intracellular pH drops, which activates the pH sensitive chlorine channels in the basolateral cell membrane. (The peak of light is an increase in the potential that follows the FOT (fast oscillation through) phase and forms the slowest and most prolonged component of the direct current electroretinogram, an event whose molecular substrate had not been elucidated until now, but the properties Melanin electrolysers explain it quite well Example 24.- Another fact that can be explained by the energizing property of melanins based on electromagnetic radiation is what refers to the intraocular pressure curve, since the pigment and the Photolysis intervenes significantly in the dynamics of aqueous humor, because during the night (dark) the production of aqueous humor decreases by 45%, and increases intraocular pressure in the early morning, this in In a normal way, and if we accept that photolysis energizes both the production and the output of aqueous humor, things are explained quite coherently, because otherwise, without taking into account said property of melanins, then the facts are contradictory, confused, and continue as before, without feet or head. Example 25.- Another observation that supports our postulates, is the fact that melanocyte stimulants (for example, beta blockers), do not act at night, that is; although we activate the melanocyte, if there is no light energy, the second part of the event is not carried out, which is a greater photolysis, hence a greater activity of the melanocyte is required but also the presence of light or electromagnetic radiation, because of otherwise there is no significant effect on intraocular pressure.

Example 26.- Other examples in this regard is that other medications that are effective in managing intraocular pressure levels all act either by inhibiting melanocyte, such as pilocarpine (the first medication useful in this regard, used by first time in the second half of the XEX century) and which is still used to date.

Example 27.-Other useful drugs that inhibit melanocyte and therefore improve circulation in patients affected by glaucomatous optic neuropathy are the antagonists of endothelin (just described as a useful treatment in disorders of aqueous humor dynamics and / or glaucomatous optic neuropathy) but which are not yet available in the market.

Therefore, I claim, pharmaceutical compositions, for the prevention or treatment of glaucomatous optic neuropathy, based on inhibitory or antagonistic compounds of endothelin E. Example 28.- The woman, during the first 14 days of the menstrual cycle, produces endothelin 1 inhibitors naturally, and it is reported in the literature, that women whose menarche is at an early age, have less glaucomatous optic neuropathy or less severe when advancing in the age, in case they present it. Example 29.- Nitric oxide donors are also described as useful in the management of glaucomatous optic neuropathy, since it is reported in the literature that people who use nitric oxide donors in a sustained manner lose less or no visual fields in cases of glaucomatous optic neuropathy and nitric oxide inhibits melanocyte. These medications are currently not available in the market for topical ophthalmological application, so they need to be prepared.

Therefore, I claim, pharmaceutical compositions, to treat prophylactic or therapeutic glaucomatous optic neuropathy.

Example 30.- Another way to treat glaucomatous optic neuropathy is to inhibit melanocyte or to activate it, as is the case with prostaglandins, their analogues or their derivatives, since they reduce intraocular pressure, a fact that can be explained by the fact that by increasing the Bioavailability of melanins, there is a greater substrate to energize the reactions involved in the dynamics of aqueous humor, although here there is a problem, the stimulants of the pigment, make the retina, enter a state of resistance to ischemia, which is in some diseases and especially during certain stages, for example diabetic retinopathy and age-related macular degeneration, but in the case of glaucomatous optic neuropathy, intraocular pressure levels tend to decrease, but because the retina uses less oxygen and the greater availability of melanin, endothelial cells tend to Apoptosis, so in the long term the patient has lower levels of intraocular pressure, but loses visual fields to a greater or lesser degree, so that this type of substance needs to be combined with melanocyte antagonists in order to balance the reactions that happen . (For example, combining with an endothelin 1 inhibitor). Example 31.- Phosphodiesterase inhibitors, that is, the activators of cyclic AMP, are substances that can activate melanocyte and therefore increase melanin synthesis, thereby inducing the retina to enter a state resistant to hypoxia, an effect that in the long term, causes the gradual disappearance of the capillaries that nourish the head of the optic nerve, so in the case of glaucomatous optic neuropathy this type of melanocyte stimulants need to be used very carefully, or combined with antagonists of endothelin El.

Example 32.- Melanocyte stimulants, in the case of diabetic retinopathy and age-related macular degeneration, are an advantage, since inducing a hypoxia-resistant state of the retina, thanks to the greater availability of the Melanin, greater availability of oxygen and therefore lower hypoxia, which is the main stimulus for neovascularization, decreases the tendency to angiogenesis.

Example 33.- An important example of the anti-angiogenic activity of melanin and / or melanocyte is the application of coherent electromagnetic radiation (LASER) in the retina to reduce rubeosis in diabetic retinopathy in proliferative stages and in related macular degeneration with the age that they proliferate, in addition to other diseases in which the development of new vessels is a serious complication, such as sickle cell anemia, retinopathy of prematurity, hypoxic neuropathies, traumas, carotid insufficiency, leukemia, etc. In such diseases, the Hypoxia is the central axis of neovascularization, and in fact, the beneficial effect of the laser in the eye is reduced to stimulate or activate melanocytes, and therefore increase the amount of melanin available; which leads to an increase in the bioavailability of oxygen and energy (hydrogen) of the tissues of both the retina and near them. Analyzed in this way, the rest of the effects of photocoagulation are actually undesirable side effects, since the formation of chorioretinal scars is inadequate, because the movements of the eye are not followed by a uniform displacement of all the layers of the eye (sclera, choroid, retina, vitreous, crystalline, cornea, conjunctiva) but due to their histological differences, each layer has a significantly different inertia, which produces or seems to explain that chorioretinal scars are areas of chronic inflammation, since the edges of said scar represent permanent small areas of chronic irritation or inflammation, due to the constant impact by inertia / traction of the tissues due to the incessant movement of the eyeball and the organism itself, something similar to burying a pin in the retina, which gives as a result of the eye movement, that the different inertia of the surrounding tissues will produce r a chronic trauma to the surrounding tissue, so this explains why, over time, laser scars (and other etiology, but scars at last) grow over time, as they increase in extent and pigmentation. A natural example of this tissue deterioration due to the constant movement of the eye, we have it on the edge of the optic nerve, which is an area where we frequently find or increase melanin, which reflects the activation of melanocytes by chronic inflammation, or either the activation of the cytochrome P 450 system, in which case the tissue is greenish with white light, and black when illuminated with 450 nanometers, and with little or no melanin, as both systems seem to antagonize, since one or the other predominates, but both eventually produce disappearance of nearby blood capillaries, whether or not they are neoformed or present at birth.

Therefore, I claim, pharmaceutical compositions as claimed in 1, to treat therapeutically or prophylactically diseases in which increasing the activity of melanocyte / melanins is advisable, as in hypoxic retinopathies. Example 34.- Another undesirable effect of the application of laser in the retina is the destruction of photoreceptors, something that is unacceptable, since it diminishes the quality of vision irreversibly, and although initially it was accepted as an important fact, now He thinks that it does not intervene significantly in the antiangiogenic effect of the laser, something that took something like 33 years to happen, another example of what is called collective errors in medicine.

Example 35.- Another example of the laser effect in the eye, is that in the literature it is reported, by the way wrong, is that the beneficial effect is that it thins the tissues and that allows greater access of oxygen from the choroid to the retina, and I write that it is wrong, because studies of choroidal circulation with indocyanine green, show that the choroidal vessels, which are under the chorioretinal scars, close significantly, often completely, so the descriptions that the intraoperative measurements of the partial tension of oxygen on the pigmented chorioretinal scars in which a greater bioavailability of oxygen in the vitreous near the retina is demonstrated, are incongruous, since it is said to be the thinnest tissue, but This is not the case, as the melanocyte layers sometimes triple, in addition to limiting the effective diffusion of oxygen in the tissue It is 100 microns, after that distance, the amount of oxygen changes so that it is not adequate to meet the metabolic tissue needs in a sustained manner. Therefore, explaining the greater amount of oxygen that is detected when illuminating chorioretinal scars is consistent with the stimulation of photolytic properties by the light of melanin contained in the same scar, rather than thinking that it comes from a choroid whose vessels are significantly closed, because in areas of intense laser application, the vessels are completely closed and the melanocytes are notoriously activated, reaching layers of 2 to 3 cells thick. Example 36.- Returning to intraoperative measurements of partial oxygen tension, in which it is shown that on chorioretinal pigmented scars (we could say hyperpigmented, since the laser or electromagnetic radiation activates melanocytes); The partial pressure of oxygen is higher than in the natural or normal pigmented retinal areas, and if we analyze the way they are done, we can demonstrate that this greater availability of oxygen is due to the photolytic properties of melanin on water , which, is available sufficiently in the ocular environment. Measurements are made after vitrectomy, and an intense light source is used, through optical fibers, which illuminates the scar area intensely, this is required, so that the observer, or surgeon, through the microscope Surgical, you can properly place and without damaging nearby tissues the oxygen sensitive probe or electrode or prove that it measures the partial pressure of oxygen, then, if there is more melanin, if the choroidal vessels underlying the scar are closed, if the tissue is thicker by the various layers of melanocytes (more than 100 microns, the usual thickness of a hair), and there is more melanin, in addition to intense light, then they gather the factors necessary for the photolysis to happen, (melanin, light and water) and the latter explains the higher concentration of oxygen in that area, because when lighting, the photolysis will happen having enough melanin and water, and this description It has no difficult parts to explain, as is the case with the wide and mistaken hypothesis of the greater diffusion of oxygen from the choroid, which in these cases has fewer vessels than normal (the choroid) and more pigment than normal. One observation: the measurement of oxygen in chorioretinal scars in the dark has not been reported because it is very difficult to do so, perhaps impossible, but once they are reported, we can observe that when there is no light, the amount of oxygen that can be measured, it descends significantly possibly to lower concentrations compared to areas where the choroidal vasculature is normal, which would not have to occur if the oxygen in the pigmented chorioretinal scars actually came from the choroidal circulation, since if so, the presence or absence of light It should not have any effect on the partial concentration of oxygen. Considering examples 35 and 36, I claim, the pharmaceutical compositions, in order to imitate the beneficial effects of the LASER, that is to say it would be equivalent to a chemical photocoagulation, avoiding the secondary or undesirable effects of the photocoagulation, according to the mechanisms of action of Melanins Example 37.- Any substance that stimulates melanocytes and / or the synthesis of melanin, will increase the availability of oxygen, and therefore hydrogen, which means energy for the cell, so substances such as nicotine, which stimulate the melanocytes indirectly through its effect on the hypothalamus, (nicotine inhibits the hypothalamus, resulting in a release of the tonic secretion of alpha MSH by the intermediate pars of the pituitary gland when the presence of dopamine decreases) they induce the retina and other tissues to enter a metabolic state of resistance to hypoxia, a potentially useful state in diseases of the retina and / or optic nerve that They have chronic ischemia / hypoxia. Considering example 9 and 37, I claim pharmaceutical compositions, which are used in therapeutic or prophylactic way to induce the retina or some other tissue to enter a hypoxic-resistant metabolic state.

Example 38.- The fact that melanocytes intervene significantly in the oxygenation of the tissues can be based on the bibliographic data of the lower concentration of hemoglobin in the blood to greater pigmentation of the skin. It is reported that there is a difference of up to 20 grams per liter of hemoglobin difference between blacks and whites. This data is also supported by the fact that the lungs are larger while the skin is lighter (better swimmers when floating easier thanks to a greater amount of air?), And they are smaller while the skin is darker. The blood (non-Newtonian liquid) is thicker or viscous in the target due to the greater amount of erythrocytes, but this gives certain advantages, for example in the cold, because they resist the cold better, thanks to the fact that there is more heat-producing units (erythrocytes for example), require less shelter and adapt better to the cold regions of the planet, this greater amount of hemoglobin is consistent with the relative hypoxia of white in relation to black, even white has anatomical differences among others, with the black rib cage, so that the larger white lungs have adequate space. Example 39.- Substances that deplete (poison) melanin, diminish its great properties, and this can be demonstrated by the fact that the greater the amount of iron in the body, more heart attacks, more parkinson's, more seizures due to hyperthermia , more gestational diabetes, more preeclampsia, more age-related macular degeneration, remember that the first two hypoxia data in any part of the body are edema and hemorrhage (Robbins 2002) and the eye is no exception. This goes hand in hand, because of the controversy that exists about the compulsory indication in some parts of the world of iron to pregnant women and children, a fact that is refuted even by experts from the world health organization, remember that once the iron penetrates, the organism has serious difficulties to get rid of excess of said element, because it only obtains it in a very slow way and through the desquamation of the skin (the iron joins the melanin and this comes off together with the keratinocytes of the skin, as well as in the hair, since the melanocytes collect iron (and other metals and substances) from the blood, incorporate it into the melanin of the hair or skin, which takes it outside the body, but slowly ). This is another example of the so-called collective medical errors, because if we are aware of the deleterious effect of iron on melanin, then we understand the need to protect the pigment by avoiding the ingestion of iron, because otherwise doctors seem not to be aware of the dangers of exaggerated doses of iron containing the compounds available in the pharmacy, since they are usually 60 mg, but our daily needs are only one mg, and therefore, the body's defenses against excess iron, they are easily violated, when we hide iron in the middle of some molecule, so that it is almost completely absorbed (59 times the required daily dose). Example 40.- There are many phenomena, both physiological and pathological, that can be explained consistently from taking into account the bioenergizing and bio-oxygenating properties of melanin from photolysis. In other examples, the photolytic property of melanin explains why dogs lose their smell at night, since the pigment, which usually saturates the nose area and therefore the specific receptor environment, loses its properties by not receiving the energy contribution that corresponds to light or electromagnetic radiation and cannot perform its function properly or optimally. Example 41.- Another example that supports our thesis in vivo is the fact that the species of animals, fish or insects that live in the dark do not have pigment and even not even eyes maybe just sketches, this could be explained by the fact that the single blood supply is not enough to support an organ as extraordinary as the eye, because to carry out the transduction of light energy into bioelectric energy, both the intense blood supply is required (the eye receives 10 times more blood per minute than the brain, 6 times more than the coronary and 3 times more than the renal cortex), as well as the energizing (hydrogen) and oxygenating contribution of melanin through photolysis, and so it is, that insects, fish, rodents who live in the eternal darkness (caves for example), lose all vestige of this prodigious organ (the eye). Example 42.- It is no coincidence that organisms, all of them eager for energy, have melanin in abundance and always directed towards light, this in fish, in mammals, in frog eggs, that although we turn them, melanin always It goes up. Example 43.- When there is not enough water, melanin fulfills other functions, such as chelating or binding multiple molecules, organic or inorganic, preventing them from entering organism, because when combined with them, in one way or another, the inactive and, thanks to the desquamation of the skin and hair growth, returns them to the outside, proof of this is that in the parts of the different animals that are found in frequent contact with the outside, for example the mouth of the mammals, the beak of the birds, the gums, the nose, the legs, the hair, that is to say, all those parts of the organism that are exposed to receive important amounts of foreign compounds, whether of animal, vegetable, mineral origin etc; and due to its nature or function, and to a greater amount of external agents, the rule is that a greater amount of melanin is observed than in the rest of the body, most likely due to the purpose of capturing substances from mastication, olfaction , the ambulation, the rubbing with the vegetables or animals that surround it or those that feed, significantly reducing its different actions on the organism in question, otherwise, we would be invaded by an extraordinary amount of compounds that would alter or perhaps they would make impossible the usual development and / or function of tissues and / or organisms. Example 44.-Among the applications that can be foreseen for the photolytic properties of melanins, we have their pharmacological manipulation for the treatment of at least the three most epidemiologically important diseases of the eyes, and that is glaucoma, since melanin and Light has much to do with the dynamics of aqueous humor and the preservation and / or disappearance of blood vessels in the optic nerve, and in age-related macular degeneration and in diabetic retinopathy, diseases in which, together with The anti-angiogenic property of melanins, their stimulation induces the retina to enter a metabolic state that makes it significantly resistant to hypoxia. Example 45.- It is very likely that as this photolytic property of melanins is known, new metabolic pathways are reported that are influenced by it, as well as new diseases, new physiological concepts and new forms of treatment for various diseases. Example 46: One of the oxygenating effects of melanins, we can observe when analyzing the dynamics of aqueous humor (in the eye) in organisms such as some canids, in which the pigmentation of the conjunctiva is very intense, unlike human, and due to the anti-angiogenic properties of melanins, the exit of the aqueous through the aqueous or episcleral veins is less than that of the human, which is about 80%, due to the lower availability of these endothelial channels or channels, charging higher importance the so-called posterior route, which in humans is something like 10% of the total, but in highly pigmented organisms of the conjunctiva is close to 60%. The anti-angiogenic effects of melanins are based on at least 4 events that are: 1.- Thanks to photolysis, melanins increase the availability of oxygen in the surrounding environment, and the single hyperoxia itself is anti-angiogenic. 2.- Melanins form covalent bonds with thiols (Langstrom 1982) so they strongly bind any organic compound containing cysteine, for example VEGF, FGF, ILGF, and others that we know induce or favor angiogenesis. 3.- Melanins bind interleukins, so they reduce these important inflammatory mediators, and 4.- Melanins are anti-inflammatory, due to their stabilizing properties on tissues, resulting in reduced production of prostaglandins, and inflammation is an indispensable requirement for neovascularization. 5.- The melanocyte produces PEDF (Dawson 1999), which is the factor with the highest antiangiogenic activity known to date. Therefore, I claim pharmaceutical compositions, for antiangiogenic purposes either in the eye or anywhere in the body

Example 47.- Life is possible without melanin, but with melanin organisms are more apt to survive, the example is albinos, for example, referring to the eyes: they do not develop a normal macula, so their vision is a tenth part of the normal, the visual pathway, which normally crosses 40%, in the albino crosses 90%, the morphology of the cornea is altered, since more often they develop a non-inflammatory ectasia of the cornea (keratoconus ). Therefore, I claim pharmaceutical compositions, for therapeutic or prophylactic purposes in localized or generalized pigment deficiencies such as albinos, in order to stimulate their pigmentation

Example 48.- In the inner ear we have the stria vascularis, which is a pigmented area, and which is known to be altered with pigment diseases, altering hearing, so another problem with the lack of pigment is that the capacity hearing is compromised, reaching the point that albinos are often deaf.

Therefore, I claim pharmaceutical compositions, which are used to improve hearing problems that can be improved with increased pigmentation or melanocyte activity.

Example 49.- There are organic compounds (catabolites) whose degradation and subsequent excretion of the body can be facilitated by increasing the bioavailability of hydrogen (energy) and oxygen, so that by stimulating melanocytes by physical or chemical means (with pharmaceutical compositions, for example ) we can better some alterations and / or diseases that occur with abnormal storage of some compounds in different organs of the body.

Therefore, I claim pharmaceutical compositions, in order to improve the elimination of catabolites through greater bioavailability of energy and / or oxygenation. Example 50.- All fibroblasts in the organism, in the presence of hypoxia, react by secreting collagen (Dr. Humberto Montoya de Lira, 2000). Stimulating the melanocyte by physical or chemical or biological methods (with pharmaceutical compositions containing, growth factors, hormones, etc.) results in a greater amount of melanin, which, according to example 46, has several routes through which it increases the bioavailability of oxygen in surrounding tissues. This has application in diseases that occur with chronic hypoxia and that cause fibroblastic proliferation, apart from those indicated in the previous examples, we will cite, in this example, specifically the premacular gliosis or macula in cellophane, which consists of the folding of the macular region thanks to the fact that the vitreous, experiences a thickening of the posterior hialoids and nearby layers, such as the internal limitation, this thickening, mainly due to a greater amount of collagen, is consistent with a greater fibroblastic activity of the cells of that area that have that capacity or that also due to hypoxia they become fibroblasts, as with some cell lines, so that, in this type of problems, activating melanocytes, or increasing the amount of melanin and thus achieving an increase in Photolysis, can result in reducing the main fibroblast activation factor, which is hypoxia. Therefore, I claim pharmaceutical compositions, With an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of premacular gliosis or macula in cellophane.

Example 51.- There are melanocytes in the epithelium of the cornea, which largely explains its extraordinary properties, given that, nowhere in the body, no cell is more than 30 microns away from a capillary. , but in the case of the corneal epithelium, the distance of the corneal epithelial cells to the capillaries of the corneal scleral limbus is 5500 microns, which is notoriously greater, but if we take into account the antiangiogenic properties of melanocyte / melanin, according to example 46; Then things start to be congruent. The importance of melanocytes in corneal avascularity is demonstrated by an experiment in 40 rats, in which, in the right eye of them, the melanocytes were selectively destroyed by a single application of hydrobenzene, 10 microliters of a 2 molar solution, and in 36 of the animals, the exposed cornea (right in all cases) developed a significant angiogenesis after two weeks, and in the left cornea (control or not exposed in all cases) no specimen had vessel development. Hydroxybenzene is a complex specific poison for melanocytes, and in the literature there are multiple reports of its selectivity, since usually tissues recover completely, except melanocytes, which disappear permanently, which is consistent with our results, as The neovascularization that developed was also permanent. According to the above, physical, chemical (pharmaceutical compositions) or biological stimulation (natural or synthetic growth factors) of the common melanocytes, it can be a curative or preventive treatment in corneal diseases that occur with angiogenesis.

Therefore I claim, pharmaceutical compositions, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of corneal angiogenesis of diverse, inflammatory, infectious, traumatic, post-surgical etiology (transplantation, pterygium or others); even idiopathic.

Example 52.- According to the previous example, in the groups of animals in which higher concentrations of hydroxybenzene (3 molar, 4 molar, 5 molar, 6 molar) were used, not only did angiogenesis develop but also an ectasia developed Non-inflammatory corneal, that is, similar to keratoconus, so that circumstantially, we find, perhaps, the only experimental model of non-inflammatory corneal ectasia (keratoconus) described to date, so it is possible that the use of compounds that stimulate Melanocytes and / or melanin could contribute to the management of such corneal problems: elevated, irregular astigmatisms, keratoconus, keratoglobo, fear, etc.

Therefore, I claim pharmaceutical compositions, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of non-inflammatory corneal ectasias such as in the case of keratoconus, keratoglobo, Fear, elevated, irregular astigmatisms, post Lásik; etc. In addition, pharmaceutical compositions, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of postoperative problems of the postlasik corneal flap, including ectasia. Also pharmaceutical compositions, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of chronic inflammation of the conjunctiva, cornea, eyelids, anterior segment, dry syndrome, vernal conjunctivitis, chronic conjunctivitis of different etiology, allergy, irritative, by contact lenses, postoperative, allergic rhinitis, allergy dermatitis, etc., that is to say for control of chronic inflammations. Example 53.- The importance of melanocytes in the epithelium of the cornea and conjunctiva, or in the anterior segment of the eye, could be an explanation to the literature reports that deal with the clearer the iris, More postoperative problems occur in the case of operative techniques in which a flap is lifted to subsequently apply laser (LASIK) so it is not remote than the stimulation of the melanocytes / melanin of the corneal epithelium, and / or the segment Previously, it may be another therapeutic or prophylactic option in the management of post Lásik corneal flap problems.

Example 54.- According to example 46, melanin and / or melanocyte has intrinsic anti-inflammatory properties, and because its molecular weight is estimated in millions, it is not absorbed, which constitutes an advantage in the curative or prophylactic treatment of Chronic inflammations of any cause of the external portions of the organism (skin and annexes, cornea and conjunctiva) since due to the ease and possibility of topical application of compounds with a suitable pharmacophore (liquid, solid, gel) it can be used for prolonged periods without the disadvantages of other anti-inflammatories (steroids for example).

Therefore, pharmaceutical compositions are claimed, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases where radiomimetic substances are used, because because melanin efficiently binds with multiple types of molecule, its application in the immediate postoperative period, including seconds after the application of the radiomimetic substance in question (mitomycin for example) which is neutralized much more effectively than the abundant irrigation with physiological serum, since the substance It is bound by melanin and therefore pharmacologically inactivated and on the other hand, melanin protects exposed tissue by its buffer properties, for example.

Example 55.- Because chelates metals, the activation of melanocyte and / or melanin can be used in problems where the concentration of some metal is too high, and since, in the case of iron, its presence is necessary for bacteria develop, then the topical application of melanin in skin and eyes, with the appropriate pharmacophore (liquid, solid, gel), that is, in the appropriate pharmaceutical composition, apart from being anti-inflammatory, it is anti-angiogenic, and because it prevents The use of iron by bacteria is indirectly anti-infectious, so the solution itself does not require preservative, which is a significant advantage in prolonged treatments. Therefore, pharmaceutical compositions are claimed, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of usual complications of the eye (inflammation, hyperhemia, secretion, different degrees of allergy) resulting from the use of lenses hard, soft, toric, therapeutic, gas permeable, etc. And also pharmaceutical compositions with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of usual complications of the eye (inflammation, hyperhemia, secretion, different degrees of allergy) resulting from the use of hard, soft contact lenses, toric, therapeutic, gas permeable, etc.

Claims

Having sufficiently described my invention, I consider as a novelty and therefore claim as my exclusive property, the content of the following clauses:

L- Pharmaceutical composition comprising an amount of effective compound, which affects the photoelectrochemical activity of melanins, directly or indirectly, in one way or another, present in biological systems, for prophylactic or therapeutic purposes.

2.-Pharmaceutical composition, as reinvindicated in 1, that includes the photoelectrochemical properties or that affects the photoelectrochemical properties of the melanins present in biological systems, so as to favor some of the reactions, which may be photolysis or photosynthesis of water.

3.- Pharmaceutical compositions according to reinvindication 1, to develop medicines that participate in the therapy of diseases that are related or are significantly affected by the properties of melanins, either photoelectrochemical or other (chelators, buffer, redox, stabilizers, etc.)

4.- Pharmaceutical compositions according to reinvindication 3, for diseases such as glaucoma, diabetic retinopathy, age-related macular degeneration, myopia, pigmentary retinosis, cataract, ischemic ocular syndrome.

5.- The use of the photoelectrochemical properties of melanins, in industrial processes based on biological systems.

6.- Pharmaceutical compositions as claimed in 1, which are used in a therapeutic or preventive way for the treatment of eye diseases that occur with hypoxia and blood deficit, for example choroidosis, optic neuropathy, ischemic eye syndrome, carotid insufficiency, and others.

7.- Pharmaceutical compositions as claimed in 1, which are used in therapeutic or prophylactic way to treat diabetic retinopathy, or age-related macular degeneration, in any of its varieties (dry or wet)

8.- Pharmaceutical compositions as claimed in 1, which are used in a therapeutic or prophylactic way to induce the retina or some other tissue to enter a metabolic state resistant to hypoxia.

9.- Pharmaceutical compositions as claimed in 1, to treat therapeutically or prophylactically non-inflammatory corneal ectasias and / or some other degenerations that can be improved by modifying the activity of melanocytes and / or melanins.

10.- Pharmaceutical compositions as claimed in 1, for the prevention or treatment of diseases that occur with an accelerated disappearance of blood vessels, such as idiopathic systemic arterial hypertension, peripheral vascular insufficiency, and the like.

11.- Pharmaceutical compositions as claimed in 1, in order to improve the events or phenomena of phototransduction or of diseases that occur with such a condition as pigmented retinosis, toxic retinopathy by xenobiotics, etc.

12.- Pharmaceutical compositions as claimed in 1, for the prevention or treatment of glaucomatous optic neuropathy, based on inhibitory or antagonistic compounds of endothelin El.

13.- Pharmaceutical compositions as claimed in 1, to treat prophylactic or therapeutic glaucomatous optic neuropathy.

14.- Pharmaceutical compositions as claimed in 1, to treat therapeutically or prophylactically diseases in which increasing the activity of melanocyte / melanins is advisable, as in hypoxic retinopathies.

15.- Pharmaceutical compositions as claimed in 1, in order to imitate the beneficial effects of LASER, that is, it would be equivalent to a chemical photocoagulation, avoiding the side or undesirable effects of photocoagulation, according to the mechanisms of action of melanins. .

16.- Pharmaceutical compositions as claimed in 1, to control the growth of blood vessels, either somewhere in the eye or anywhere in the body.

17.- Pharmaceutical compositions as claimed in 1, for therapeutic or prophylactic purposes in localized or generalized pigment deficiencies such as albinos, in order to stimulate their pigmentation.

18.- Pharmaceutical compositions as claimed in 1, which are used to improve hearing problems that can be improved with increased pigmentation or melanocyte activity.

19.- Pharmaceutical compositions as claimed in 1, in order to improve the elimination of catabolites through greater bioavailability of energy and / or oxygenation.

20.- Pharmaceutical compositions as claimed in 1, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of premacular gliosis or macula in cellophane.

21.- Pharmaceutical compositions as claimed in 1, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of corneal angiogenesis of diverse, inflammatory, infectious, traumatic, post-surgical etiology (transplantation, pterygium or others); even idiopathic.

22.- Pharmaceutical compositions as claimed in 1, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of non-inflammatory corneal ectasias such as keratoconus, keratoglobus, Terrien, elevated, irregular astigmatisms, post Lasik; etc.

23.- Pharmaceutical compositions as claimed in 1, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of postoperative problems of the postlasik corneal flap, including ectasia.

24.- Pharmaceutical compositions as claimed in 1, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of chronic inflammation of the conjunctiva, cornea, eyelids, anterior segment, dry syndrome, vernal conjunctivitis, conjunctivitis Chronic of different etiology, allergy, irritative, by contact lenses, postoperative, allergic rhinitis, allergy dermatitis, etc., that is to say for the control of chronic inflammations of different etiology (allergic, autoimmune, irritative, infectious, etc).

25.- Pharmaceutical compositions as claimed in 1, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of recurrent infections of the cornea or conjunctiva, as in the cases of dry syndrome, spring conjunctivitis, etc.

26.- Pharmaceutical compositions as claimed in 1, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of usual complications of the eye (inflammation, hyperhemia, secretion, different degrees of allergy) result of the use of hard, soft, toric, therapeutic, gas permeable contact lenses, etc.

27.- Pharmaceutical compositions as claimed in 1, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases where radiomimetic substances are used and it is desired to protect the tissue exposed thereto.

28.- Pharmaceutical compositions as claimed in 1, with an adequate route of administration and effective dose, for therapeutic or prophylactic purposes in cases of chronic inflammation of the skin, mucous membranes and anterior segment of the eye, such as allergic rhinitis, repetitive infections, dermatitis chronicle; etc.

29.- Pharmaceutical compositions, as reinvindicated in 1, or melanin itself, its precursors, its analogues or its derivatives, in order to functionally or anatomically modify cells, tissues, organs or systems; in one way or another, directly or indirectly, as a therapeutic or prophylactic measure.