ES2879173A1 - Combined preparation of a cyanobacterium and a fluorescent inorganic compound (Machine-translation by Google Translate, not legally binding) - Google Patents

Abstract

The invention describes a combined preparation comprising: a fluorescent inorganic compound that receives infrared radiation and, in response, emits visible light radiation; and a cyanobacterium that receives visible light radiation and, in response, releases oxygen. This combined preparation can be used in combination with infrared radiation for the prevention, amelioration, alleviation and/or treatment of hypoxic diseases. A kit consisting of said preparation and a device for applying infrared radiation to the patient is also described, as well as said device for applying infrared. (Machine-translation by Google Translate, not legally binding)

Description

DESCRIPTION

Combined preparation of a cyanobacterium and a fluorescent inorganic compound

OBJECT OF THE INVENTION

The invention belongs in general to the field of medicine, and more particularly to the treatment of oxygen-deficient diseases.

The object of the present invention is the use of a new combination of cyanobacteria and inorganic particles that allows the generation of oxygen in tissues affected by hypoxia.

BACKGROUND OF THE INVENTION.

Cyanobacteria are unicellular organisms capable of oxygenic photosynthesis, releasing oxygen in response to the absorption of light radiation thanks to pigments present in their plasma membranes. In most cyanobacteria, the range of wavelengths capable of causing photosynthesis is within the visible range of the electromagnetic spectrum.

In recent years, the use of certain cyanobacteria has been proposed in the oxygenation of biological media. Studies have been carried out showing that the introduction of these cyanobacteria into the biological medium and the illumination of the medium with a light source allow an improvement in the oxygenation of said biological medium. It has also been proven that cyanobacteria are not toxic to the biological environment. However, these methods have the significant drawback that they require the application of light radiation in situ, that is, within the body itself, since the visible light radiation is not capable of passing through biological tissues sufficiently to be applied from outside the body. Body.

DESCRIPTION OF THE INVENTION

The present invention is based on the use of inorganic fluorescent materials capable of upconversion of received light radiation, that is, of receiving radiation at a first wavelength and, in response to it, emitting radiation at a second wavelength. wave smaller than the first. Specifically, the inorganic materials used in the present application they emit visible light radiation in response to the absorption of infrared radiation. The use of this type of inorganic materials is especially advantageous in this context because, as is known, infrared radiation penetrates various media, and particularly biological media such as tissues, more easily than visible radiation.

Indeed, Fig. 1 of the present application shows the intensity of the emission luminescence of fluorescent inorganic materials, specifically a combination of NaYF4: Yb, Er and / or NaYF4: Yb, Tm, as well as the absorption wavelengths of the pigments of various types of cyanobacteria. It can be seen how the fluorescence peaks of the combination of NaYF4: Yb, Er and / or NaYF4: Yb, Tm overlap with several of the cyanobacterial pigments, which is sufficient for their excitation and therefore, for cyanobacteria carry out the photosynthesis process.

In view of this, the present invention describes the introduction into the body of a patient of a combination of cyanobacteria with an inorganic fluorescent material and the subsequent illumination of the patient's body with infrared radiation. The inorganic fluorescent material receives the part of said infrared radiation capable of passing through the patient's tissues and, in response, emits visible light radiation inside the tissues themselves. Cyanobacteria absorb this visible light radiation and, thanks to oxygenic photosynthesis, release oxygen. The released oxygen is absorbed by the surrounding tissues, improving their recovery.

Combined preparation of the invention

Therefore, a first aspect of the invention refers to a combined preparation, hereinafter combined preparation of the invention, comprising:

- an inorganic fluorescent compound, and

- a cyanobacterium,

By "fluorescent inorganic compound" is understood herein a fluorescent inorganic material capable of emitting visible light radiation in response to absorption of infrared radiation.

In this specification, cyanobacteria is understood as a cellular organism of the Superkingdom Bacteria, group Terrabacteria, group Cyanobacteria / Melainabacteria, and Phylum Cyanobacteria. Formerly called blue-green algae, they are an edge of the Bacteria domain that comprises bacteria capable of oxygenic photosynthesis. They are the only prokaryotes that carry out this type of photosynthesis, which is why they were also called oxyphotobacteria.

The terms " combined preparation" or " juxtaposition " herein refer to the fact that the components of the combined preparation do not need to be present as a bond, for example, in a true composition, in order to be available for their combined, separate application. or sequential. In this way, the expression " juxtaposed " implies that it is not necessarily a true combination, in view of the physical separation of the components.

Medical uses of the invention

As mentioned above, the fluorescent inorganic material emits visible light radiation in response to the absorption of infrared radiation, and the cyanobacterium releases oxygen in response to the absorption of such visible light radiation. This allows the use of the combined preparation of the invention, in combination with the emission of infrared radiation, in the prevention, improvement, alleviation and / or treatment of diseases that cause hypoxia (that is, diseases that cause oxygen deficiency) .

Therefore, another aspect of the invention relates to the combined preparation of the invention for use as a medicine, or for use in therapy.

Another aspect of the invention relates to the combined preparation of the invention for use in combination with infrared radiation in the prevention, amelioration, alleviation and / or treatment of hypoxic diseases.

Previous studies have shown the union of metallic nanoparticles to cyanobacteria, forming complexes that allow their survival and the improvement of their properties. Preferably, the cyanobacterium contains at least one of the following pigments: carotenoids, chlorophyll a, chlorophyll b, or chlorophyll f. In a particularly preferred embodiment, the cyanobacterium is of the genus Synechococcus ( Synechococcus sp.). and even more preferably it is from the Synechococcus elongatus species.

Small subunit ribosomal RNA is a useful phylogenetic marker that has been widely used for evolutionary analysis.

Synechococcus elongatus is understood herein as a cellular organism of the Superkingdom Bacteria, Terrabacteria group, Cyanobacteria / Melainabacteria group, and Phylum Cyanobacteria. Order Synechococcales, Family Synechococcaceae, and Genus Synechococcus. Any organism having a mitochondrial 16S sequence with an identity of at least 80%, more preferably 85%, 90%, 95%, 96%, 97%, 98% or 99% with SEQ ID NO is also understood. : 1. Even more preferably has a 16S mitochondrial sequence with 100% identity to SEQ ID NO: 1

SEQ ID NO: 1 AAAATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGC AAGTCGAACGGGCTCTTCGGAGCTAGTGGCGGACGGGTGAGTAACGCGTGAGAATCT GCCTACAGGACGGGGACAACAGTTGGAAACGACTGCTAATACCCGATGTGCCGAGAGG TGAAACATTTATGGCCTGTAGATGAGCTCGCGTCTGATTAGCTAGTTGGTGGGGTAAGG GCCTACCAAGGCGACGATCAGTAGCTGGTCTGAGAGGATGATCAGCCACACTGGGACT GAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATTTTCCGCAATGGGCG CAAGCCTGACGGAGCAACGCCGCGTGGGGGAGGAAGGTTTTTGGACTGTAAACCCCTT TTCTCAGGGAAGAAGAAAGTGACGGTACCTGAGGAATAAGCCTCGGCTAATTCCGTGC CAGCAGCCGCGGTAATACGGGAGAGGCAAGCGTTATCCGGAATTATTGGGCGTAAAGC GTCCGCAGGCGGTTAATCAAGTCTGTTGTCAAAGCGTGGGGCTCAACCTCATACAGGC AATGGAAACTGATTGACTAGAGTATGGTAGGGGTAGCGGGAATTCCAGGTGTAGCGGT GAAATGCGTAGATATCTGGAAGAACACCAGCGGCGAAAGCGCGCTACTGGGCCATAAC TGACGCTCATGGACGAAAGCTAGGGGAGCGAAAGGGATTAGATACCCCTGTAGTCCTA GCCGTAAACGATGAACACTAGGTGTTGCGTGAATCGACCCGCGCAGTGCCGTAGCCAA CGCGTTAAGTGTTCCGCCTGGGGAGTACGCACGCAAGTGTGAAACTCAAAGGAATTGA CGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGATGCAACGCGAAGAACCT TACCAGGGTTTGACATCCCCCGAATCTCTTGGAAACGAGAGAGT GCCTTCGGGAGCGG GGAGACAGGTGGTGCATGGCTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCC CGCAACGAGCGCAACCCACGTTTTTAGTTGCCATCATTCAGTTGGGCACTCTAGAGAAA CTGCCGGTGACAAACCGGAGGAAGGTGTGGACGACGTCAAGTCATCATGCCCCTTACA TCCTGGGCTACACACGTACTACAATGCTCCGGACAGCGAGACGCGAAGCCGCGAGGT GAAGCAAATCTCCCAAACCGGGGCTCAGTTCAGATTGCAGGCTGCAACTCGCCTGCAT GAAGGCGGAATCGCTAGTAATCGCAGGTCAGCATACTGCGGTGAATACGTTCCCGGGC CTTGTACACACCGCCCGTCACACCATGGAAGTTGGCCATGCCCGAAGTCGTTACCCTAA CCGTTCGCGGAGGGGGGCGCCGAAGGTAGGGCTGATGACTGGGGTGAAGTCGTAACA AGGTAGCCGTACCGGAAGGTGTGGCTGGATCACCTCCTTT

In another preferred embodiment of the invention, the fluorescent inorganic compound comprises at least one trivalent lanthanide ion. More preferably, the fluorescent inorganic compound comprises at least

to. a nanoparticle of NaYF4: Yb, Er, which emits radiation at different peaks in a range from blue to red, or

b. a nanoparticle of NaYF4: Yb, Tm, which emits radiation in peaks from red to near infrared, or

c. any of its combinations.

Even more preferably, the nanoparticles have a crystalline structure in a hexagonal phase and a size comprised between 100-500 nm. These sizes and structures are more stable and have a higher light intensity, as the inventor of the present application has verified through various tests with other types of structures. For example, it has been determined that the cubic structure, at first glance more suitable due to its smaller size, turns out to be unstable due to its tendency to agglomerate with heat, and also has a low luminous intensity compared to the crystalline structure in hexagonal phase. .

The term "hypoxia" or "hypoxic disorder" refers to a condition in which there is insufficient level of oxygen delivered to the blood or to the tissues and organs. Hypoxic disorders can occur through a variety of mechanisms including when there is insufficient capacity of the blood to carry oxygen (i.e. anemia), when there is inadequate blood flow to the tissue and / or organ caused by either heart failure or due to blockage of blood vessels and / or arteries (i.e. ischemia), when there is reduced barometric pressure (i.e., altitude sickness at high altitudes), or when dysfunctional cells are unable to make use of oxygen properly (i.e., conditions histotoxic). Accordingly, one skilled in the art will readily appreciate that the present invention is useful in treating a variety of hypoxic conditions including anemia, heart failure, coronary artery disease, thromboembolism, stroke, angina pectoris, and the like, including SARS. .

Therefore, in another preferred embodiment of the invention, the hypoxic disease is selected from:

to. diseases where there is insufficient capacity of the blood to carry oxygen, such as anemia,

b. diseases where there is inadequate blood flow to the tissue and / or organ caused by heart failure or by blockage of blood vessels and / or arteries, such as ischemia,

c. diseases in which there is reduced barometric pressure, such as altitude sickness, or

d. diseases in which dysfunctional cells are unable to use oxygen properly, ie, histotoxic conditions.

In another preferred embodiment, the hypoxic disease is cardiac ischemia. In another preferred embodiment, the hypoxic disease is respiratory failure.

The composition or the combined preparation of the invention can be administered to the subject suffering from said pathologies, by any of the following routes, but not limited to: intraperitoneal, intravenous, intramuscular, subcutaneous, intracecal, intraventricular, oral, enteral, parenteral, intranasal or dermal. In a preferred embodiment, the routes of administration are preferably the intravenous route and the oral route.

Preferably, when the disease presenting hypoxia is cardiac ischemia, the administration of the combined preparation is carried out intravenously. Preferably, when the hypoxic disease is respiratory failure, the administration of the combined preparation is carried out by a mouth or nasal spray.

Respiratory failure is a disease in which oxygen levels in the blood decrease or carbon dioxide levels rise in the blood in dangerous ways. Diseases that block the airways, damage lung tissue, weaken the muscles that control breathing, or decrease the drive to breathe can cause respiratory failure. Patients may suffer from dyspnea, bluish discoloration of the skin, and confusion or drowsiness. Doctors use a fingertip sensor (pulse oximetry) to detect low concentrations of oxygen and blood tests to detect high concentrations of carbon dioxide in the blood. Oxygen is supplied. Sometimes affected people need a respirator until the underlying problem can be treated. Acute respiratory failure is a medical emergency that can be caused by a chronic lung disease that suddenly gets worse, or a severe lung disease that develops suddenly in healthy people. Acute respiratory distress syndrome (ARDS) is an example of a lung disease that evolves suddenly. Chronic respiratory failure is a progressive respiratory problem that can result from long-term lung disease, such as chronic obstructive pulmonary disease (COPD).

ARDS is the common immunopathological event for infections by various viruses, bacteria, and other respiratory microorganisms, such as SARS-CoV-2, SARS-CoV, and MERS-CoV. One of the main mechanisms for ARDS is the so-called cytokine storm. The uncontrolled fatal systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines (IFN-a, IFN-y, IL-1p, IL-6, IL-12, IL-18, IL-33, TNF-a, TGFp, etc.) and chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9, CXCL10, etc.) by immune effector cells.

Therefore, another preferred embodiment refers to the combined preparation of the invention for the prevention, amelioration, relief and / or treatment of acute respiratory distress syndrome (ARDS).

In another preferred embodiment of the invention, the emitted infrared radiation has a wavelength between 850 nm and 1100 nm, more preferably between 950 nm and 1000 nm. This wavelength range is selected to elicit the highest possible light intensity from inorganic particles. The maximum value is believed to be obtained with infrared radiation of approximately 980 nm, since the ytterbium (Yb) present in inorganic particles excites their electrons at that particular wavelength.

The administered amount of the combined preparation of the present invention will depend on the relative efficacy of the chosen compound, the severity of the disease to be treated and the weight of the patient. However, preferably, the combined preparation of this invention will be administered one or more times a day, for example 1, 2, 3 or 4 times daily, with a total dose between 0.1 and 1000 mg / Kg / day. It is important to bear in mind that it may be necessary to introduce variations in the dose, depending on the age and condition of the patient, as well as modifications in the route of administration.

Cyanobacteria survive approximately 24 hours in internal body conditions. Once the combined preparation is introduced into the patient's body, the radiation application time can be between a few minutes, such as 10, 20, 30, 40, 50, or 60 minutes, and a few hours, such as 1 , 2, 3, 4, 5 or 6 hours. The application of radiation can be done in a single session or divided into several sessions. The application Infrared radiation can be performed intermittently according to a pulse width modulation (PWM) scheme to avoid damaging the patient's skin.

The combined preparation of the present invention, as well as the pharmaceutical compositions containing it, can be used together with other drugs, or additional active ingredients, to provide a combination therapy. Said additional drugs can be part of the same combined preparation or, alternatively, they can be provided in the form of a separate composition for their simultaneous administration or not with that of the combined preparation of the invention.

The term " drug ", as used herein, refers to any substance used for the prevention, diagnosis, alleviation, treatment or cure of diseases in human and animal subjects.

Both the compositions of the present invention, as well as the combined preparation or dosage forms of the invention, can be formulated for administration to an animal, and more preferably to a mammal, including humans, in a variety of ways known in the art. state of the art. Thus, they can be, without limitation, in sterile aqueous solution or in biological fluids, such as serum. Aqueous solutions can be buffered or unbuffered and have additional active or inactive components. Additional components include salts to modulate ionic strength, preservatives including, but not limited to, antimicrobial agents, antioxidants, chelators, and the like, and nutrients including glucose, dextrose, vitamins, and minerals. The compositions can be combined with various inert carriers or excipients, including but not limited to; binders such as microcrystalline cellulose, gum tragacanth, or gelatin; excipients such as starch or lactose; dispersing agents such as alginic acid or cornstarch; lubricants such as magnesium stearate, glidants such as colloidal silicon dioxide; sweetening agents such as sucrose or saccharin; or flavoring agents such as peppermint or methyl salicylate.

Such compositions or combined preparations and / or their formulations can be administered to an animal, including a mammal, and thus to humans, in a variety of ways, including, but not limited to, intraperitoneal, intravenous, intramuscular, subcutaneous, intracecal. , intraventricular, oral, enteral, parenteral, intranasal or dermal.

The dosage to obtain a therapeutically effective amount depends on a variety of factors, such as age, weight, sex, tolerance, etc. of the mammal. In the sense used in this description, the expression " therapeutically effective amount " refers to the amount of which the active principle or principles of the invention comprises that produce the desired effect and, in general, will be determined, among other causes, by the characteristics of the combined preparation of the invention and, optionally, said prodrugs, derivatives or analogs, and the therapeutic effect to be achieved. The " adjuvants " and "pharmaceutically acceptable vehicles " that can be used are the vehicles known to those skilled in the art.

Invention kit

Another aspect of the invention refers to a kit comprising the combined preparation of the invention, and further comprising a device for the application of infrared radiation to an individual or patient. The device may take a form of garment that the patient can easily wear, such as, without limitation, a vest, a shirt, a T-shirt, a hat, a cap, a shoe, a sleeve, a leg, a thigh brace, a calf brace, a knee brace, a wrist brace, a scarf, a band around the chest, etc. This device in the form of a garment may have at least one source of infrared radiation arranged on its inner face and oriented towards the skin of the patient for the purpose of supplying the infrared radiation to the supplied combined preparation. More preferably, this garment has a plurality of sources of infrared radiation, for example infrared LEDs, distributed on its inner face. In particular, according to a particularly preferred embodiment of the invention, the device formed by a garment is a vest that covers the thoracic area of the patient. The garment may further comprise a controller connected to the infrared radiation sources to cause their intermittent ignition in order to avoid damage to the skin of the patient.

Thus, in the particular case that the garment is in the form of a vest, the plurality of infrared excitation LEDs distributed on the inside of the vest emit light radiation directly on the skin of the thoracic area of the patient, mainly chest and chest. back. Part of this radiation passes through the skin of the patient until it reaches the place where the combined preparation of the invention has been introduced, for example, the lungs or the cardiac area, thus causing the generation of oxygen according to the processes previously described in this document. Controller controls ignition flashing LEDs to avoid causing harm to the patient.

Device of the invention

Another aspect of the invention is directed to a device for the application of infrared radiation to a patient that comprises a garment configured to be worn by the patient and equipped with at least one source of infrared radiation arranged on its inner face and oriented towards the patient's skin. The device may take a form of garment that the patient can easily wear, such as, without limitation, a vest, a shirt, a T-shirt, a hat, a cap, a shoe, a sleeve, a leg, a thigh brace, a calf brace, a knee brace, a wrist brace, a scarf, a band around the chest, etc. Preferably, this garment has a plurality of sources of infrared radiation, for example infrared LEDs, distributed on its inner face. In particular, according to a particularly preferred embodiment of the invention, the device formed by a garment is a vest that covers the thoracic area of the patient. The garment may further comprise a controller connected to the infrared radiation sources to cause their intermittent ignition in order to avoid damage to the skin of the patient.

Throughout the description and claims the word " comprise " and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and characteristics of the invention will emerge in part from the description and in part from the practice of the invention. The following examples and drawings are provided by way of illustration, and are not intended to be limiting of the present invention.

BRIEF DESCRIPTION OF THE FIGURES

Fig. 1 shows a graph showing the emission peaks of the combination of nanoparticles NaYF4: Yb, Er and NaYF4: Yb, Tm and the absorption peaks of different types of cyanobacteria.

Fig. 2 shows an example of a vest equipped with infrared LEDs according to the invention.

PREFERRED EMBODIMENT OF THE INVENTION

Obtaining the combined preparation

First, the procedure that is carried out to obtain the combined cyanobacteria-particle preparation is briefly described. Thanks to previous studies by the inventors, it is known that the preparation can be obtained by the following synthesis method.

A solvothermal synthesis is carried out, in a conventional oven for 24 hours at 230 ° C. It is well known that this synthesis is obtained from a stock solution containing nitrates of the inorganic elements that provide luminescence to the particle, well known as trivalent lanthanide ions. For luminescence to occur, the presence of three types of lanthanide ions is necessary, which act as stabilizer, sensitizer and activator. The correspondence between the two has been well studied and known to obtain maximum luminescence, this being in number of moles: X of stabilizer, 0.2 X of sensitizer and 0.02X of activator.

The matrix used to provide stability to the particle will be the well-known NaYF4, obtained from the precursors NH4F and NaOH, in the ideal proportion so that the mixture prior to synthesis is at an acidic pH of 5.

The sensitizer used will be Yb, due to its great stability and its emission spectrum, while the activators will be Tm and Er, thanks to the fact that their emission spectra coincide with the absorption peaks of S. elongatus.

The combination between cyanobacteria and inorganic particles will be carried out by means of a simple wet deposition with the use of a rotary evaporator. The inorganic material thus adheres to the surface of the cyanobacteria.

Application of the combined preparation

Once the combined preparation has been obtained, it is administered to the patient. Delivery to the patient is carried out in such a way that the preparation reaches those tissues of the patient where the lack of oxygen is occurring. For example, in the case of using the combined preparation of the invention for the treatment of cardiac ischemia, said preparation is introduced intravenously. The blood circulation thus carries the preparation to the heart. Alternatively, if the combined preparation is to be used For the treatment of respiratory failure, the application of said preparation is carried out through the patient's airways, for example in the form of an aerosol delivered by means of an oral or nasal inhaler.

Infrared radiation illumination

Once the combined preparation of the invention is housed in the tissues of the patient to be treated, infrared illumination is applied to the skin in the area closest to said tissues. For example, in the case of the treatment of cardiac ischemia or respiratory failure, infrared illumination is applied over the entire thoracic area and the patient's back. For this, a specially designed device is used to maximize the applied lighting.

The device of this example takes the form of an open vest that is closed, for example, by a zipper. In any case, it should be noted that the characteristics of the vest described below are applicable to a device in the form of any other garment, according to the needs of each particular application.

The vest can be made of any suitable material, such as a textile material such as lycra. The inner face of the vest comprises a plurality of infrared excitation LEDs facing inward, that is, towards the skin of the patient when wearing the vest. In this example, the infrared LEDs are arranged essentially uniformly so that they cover the entire inside face of the vest, although it would be possible to design garments in which the LEDs are arranged only in certain areas of interest corresponding to those parts of the body. of the user where the treatment is to be applied. The distance between adjacent LEDs will be approximately 1 cm, although depending on the size, shape and intensity of radiation desired it would be possible to use other arrangements. This configuration allows the entire thoracic area and back of the patient to be illuminated essentially uniformly. The wavelength will be as close as possible to 980 nm, or in any case within the range of 850-1150 nm, corresponding to the range of absorption wavelengths of fluorescent nanoparticles.

The vest also has a power battery connected to the LEDs. In order not to reduce the irradiation surface, the battery can be fixed to the outer face of the vest. For example, it can be housed in an outer pocket. The battery powers the LEDs with a voltage between 1.2-1.3 V across, for example, a 1 mm diameter wire. LEDs with these characteristics support an intensity between 20 - 30 mA, thus establishing a power of between 0.024 - 0.036 W, enough to avoid the appearance of burns in the tissues.

Depending on the power of the LEDs, it may be necessary to control their operation in order to avoid excessive heating of the patient's skin. This is done in this example using Pulse Width Modulation (PWM). Thus, LEDs follow a repeating cycle of on and off sequences. For this, the vest can also have a simple processing means, such as a microprocessor, microcontroller, ASIC, FPGA, DSP, or in general any control device capable of controlling the on / off of the LEDs.

Next, the duty cycle of the LEDs is calculated to avoid burns to the patient.

Thanks to Plank's law we know the energy emitted by a wavelength, as shown in Equation 1.

E = h • f (Equation 1)

where

h is Plank's constant = 6.626 .10-34 Js

f is the frequency of the wavelength.

Thanks to the knowledge of the wavelength, the frequency of the infrared radiation used can be calculated, which is observed by Equation 2.

(Ecuación 2)

(Equation 2)

A = lo ng itu d wave = 800 - 1000 nm

Applying equation 2 to the limit values of the wavelengths emitted by the LEDs, is obtained:

3,108

/ i = 3.75.10_4s_1

8 . 1011

3,108

fi = 3.10-4 5_1

1 . 1012

Consequently, applying Equation 1 it is determined that the energy range will be between E1 and E2:

Knowing that the average temperature of the body is 36 ° C and that the maximum temperature that the skin can withstand without causing damage is 50 ° C, it is possible to determine the amount of heat that the skin could absorb and, with it, the working time in continuous of the LEDs. For this, the expression of the specific heat shown in Equation 3 is used.

(Ecuación 3)

(Equation 3)

Applying this equation to the energy value Ei corresponding to the most energetic infrared radiation, with a wavelength of 800 nm, we obtain:

2. 5.1 037

1.8.10 "38 // ° C

50 - 36

This quantity represents the energy released by temperature. To know the time, the previous calculations will have to be inverted and the range with the highest energy will be selected, using the expression of the period, represented in Equation 4.

Therefore, to avoid damaging the skin, the LEDs will follow a duty cycle consisting of between 30 - 40 seconds of operation and 30 seconds of rest.

Claims (27)

1. Combined preparation comprising: to. a fluorescent inorganic compound and b. a cyanobacterium. 2. The combined preparation according to the preceding claim, for use in medicine. The combined preparation according to any of claims 1-2, for use in combination with infrared radiation in the prevention, amelioration, alleviation and / or treatment of hypoxic diseases. 4. The combined preparation according to claim 3, wherein the emitted infrared radiation has a wavelength between 850 nm and 1100 nm. 5. The combined preparation according to claim 4, wherein the emitted infrared radiation has a wavelength between 950 nm and 1000 nm. 6. The combined preparation according to any of claims 1-5, wherein the cyanobacterium contains at least one of the following pigments: carotenoids, chlorophyll a, chlorophyll b, and chlorophyll f. 7. The combined preparation according to any of claims 1-6, wherein the cyanobacterium is of the genus Synechococcus. 8. The combined preparation according to any of claims 1-7, wherein the cyanobacterium is from the Synechococcus elongatus species. 9. The combined preparation according to any of claims 1-8, wherein the fluorescent inorganic compound comprises at least one trivalent lanthanide ion. The combined preparation according to claim 9, wherein the fluorescent inorganic compound comprises at least: to. a nanoparticle of NaYF4: Yb, Er, which emits radiation at different peaks in a range from blue to red, or b. a nanoparticle of NaYF4: Yb, Tm, which emits radiation in peaks from red to near infrared, or c. any of its combinations. 11. The combined preparation according to claim 10, wherein the fluorescent organic compound has a crystalline structure in hexagonal phase and a size comprised between 100-500 nm. 12. The combined preparation according to any of claims 3-11, wherein the hypoxic disease is selected from: to. diseases where there is insufficient capacity of the blood to carry oxygen, such as anemia, b. diseases where there is inadequate blood flow to the tissue and / or organ caused by heart failure or by blockage of blood vessels and / or arteries, i.e. ischemia, c. diseases in which there is reduced barometric pressure, such as altitude sickness, or d. diseases in which dysfunctional cells are unable to use oxygen properly, ie, histotoxic conditions. The combined preparation according to any one of claims 3-11, wherein the disease leading to hypoxia is cardiac ischemia. The combined preparation according to claim 13, wherein the administration of the combined preparation is performed intravenously. 15. The combined preparation according to any of claims 3-11, wherein the hypoxic disease is respiratory failure. 16. The combined preparation according to claim 15, wherein the administration of the combined preparation is carried out by means of an oral or nasal spray. 17. Kit comprising the combined preparation according to any of claims 1-16, further comprising a device for applying infrared radiation to a patient. 19 18. The kit according to claim 17, wherein the device for applying infrared radiation to a patient is a garment configured to be worn by the patient and equipped with at least one source of infrared radiation arranged on its inner face and oriented towards the patient's skin. 19. The kit according to claim 18, wherein the garment comprises a plurality of sources of infrared radiation distributed on its inner face. 20. The kit according to any of claims 17-19, wherein the infrared radiation sources are infrared LEDs. 21. The kit according to any of claims 17-20, wherein the garment is a vest that covers a thoracic area of the patient. 22. The kit according to any of claims 17-21, wherein the garment further comprises a controller that turns on the infrared radiation sources intermittently to avoid causing burns to the patient's skin. 23. Device for applying infrared radiation to a patient, comprising a garment configured to be worn by the patient and equipped with at least one source of infrared radiation arranged on its inner face and facing the patient's skin. 24. Device according to claim 23, comprising a plurality of sources of infrared radiation distributed on its inner face. 25. Device according to any of claims 23-24, wherein the sources of infrared radiation are infrared LEDs. 26. Device according to any of claims 23-25, wherein the garment is a vest that covers the thoracic area of the patient. 27. Device according to any of claims 23-26, wherein the garment also comprises a controller that turns on the infrared radiation sources intermittently to avoid causing burns to the patient's skin.