WO2019173884A1 - Biological normalizer, process for producing a biological normalizer and products produced with the biological normalizer - Google Patents

Abstract

The present specification relates to an invention patent application for a biological normalizer, pertaining to the field of medicines, which was developed on the basis of observations that an aqueous solution of phospholipid liposomes and micelles has biological properties and serves as a basis for applications mainly for external use, directly on the dermis, in body cavities with a serous or mucous lining and in pathological cavities, such techniques not having been used until now and constituting the biological normalizer; said biological normalizer, in one main embodiment, being a solution 1 of cell membrane phospholipid liposomes and micelles in a proportion of 0.01-10.00 g in one litre of diluent; said solution 1 being pure or combined (by adhesion by means of opsonization) with a useful biological substance(s) and/or medicine(s).

Description

“BIOLOGICAL NORMALIZER, PROCESS FOR OBTAINING BIOLOGICAL NORMALIZER AND PRODUCTS OBTAINED FROM BIOLOGICAL NORMALIZER”

 [001] INTRODUCTION - This descriptive report relates to a patent application for biological normalizer, which pertains to the field of general adjuvant medicinal products for organism, which has been developed in view of the observation that the aqueous solution Phospholipid liposomes and micelles have biological properties, which make advances in technical knowledge, inventive activities, industrial applications and formulations offering new utilities that serve as the basis, in this patent application, for applications with the primary purpose of external use, directly over the dermis, in serous or mucosal covered body cavities and pathological cavities, techniques that have not been used to date and which constitute the biological normalizer.

[2] BACKGROUND OF THE INVENTION - Known General Properties of Cellular or Synthetic Membrane Phospholipids - Phosphidipethanolamine, phosphatidylcholine, sphingomyelin, phosphatidylserine and phosphatidylinositol are found in all living things. , forming their cell membranes. They may be accompanied, in nature, by phosphatidic acid, triglycerides, glycolipids, carbohydrates, pigments, caretenoids and other non-toxic microcomposites. Each type of phospholipid has a biochemical principle skeleton retaining the nomenclature, but has a wide variety of combinations in its lipid chains. The formation of uni or multilamellar liposomes and micelles is a physical property natural and spontaneous phospholipids when diluted in water. Liposomes are divided into multilamellar vesicles (MLV) of diameter 400 to 3500 pm (micrometer), unilamellar vesicles (LUV) of diameter 200 to 1000 pm, and small unilamellar vesicles (SUV) of diameter 20 to 50 pm; micelles have a diameter of 0.1 to 0.001 pm. These divisions are not used in this patent application.

 [3] Cell membrane phospholipids can be extracted from soy, eggs, cereals, nervous tissue (brain and spinal cord) or any other biological matter in the body. They are absorbed during digestion, formed in the liver and abundant in the plasma as HDL. They are also fully metabolized natural products and are not excreted from the body in faeces or urine, considered and classified by FoodandDrug in the United States as safe non-toxic edible substances for the human body and an overdose is not known. . In the European Union they are recognized as food additives. Cell membrane phospholipids are present in the national and international pharmaceutical markets in dry granular form, dense emulsion or capsules.

[4] Cell membrane phospholipids are formed of amphipathic molecules. Each molecule has a positively and negatively charged hydrophilic and / or lipophobic dipolar head and a contralateral tail formed of long hydrophobic and / or lipophilic variable fatty acid chains. These properties allow cell membrane phospholipid molecules to align and stabilize in aqueous solution, forming a double layer of micelles and vesicles called liposomes filled with liquid diluent of smaller than a cell, separating the aqueous solution in the lumen (cavity or center) on the outside of the liposome and facing the hydrophilic polar ends on both sides of the bilayer. The tail (fatty acid chain) is in the middle of the double layer surrounded on both sides by ionic layers (the heads) separating the inner lumen from the outer liposome space. Page 1246, 27.8- Organic Chemistry Book, 8. Edition, by CALOUSTE GULBENKIAN FOUNDATION (see attached figures 1 to 3, in which figure 1 shows a simple lipoid bilayer model; figure 2 shows the sectioned liposome perspective laminar, and Figure 3 shows the perspective laminar section micelle).

 [5] Mononuclear macrophages play a role in informing pathological changes in the body to the immune system to activate the non-specific immune response, and another function of phagocytosis is the uptake of opsonins, liposomes and micelles.

 [6] Opsonins are receptor molecules on the cell surface and others, they facilitate phagocytosis and activate the complement system in the body that eliminate (opsonization) antibodies, proteins, liposomes and micelles.

 [7] Liposomes and micelles such as opsonins facilitate the functions of mononuclear macrophages and activate the complement system, nonspecific defense and order of vital processes in the body; Injection of the liposome and micelle solution into the living organism does not elicit a specific immune response.

[8] BACKGROUND ART - Current use of cell membrane phospholipids - Phospholipids are currently used as: [9] 1 - Oral nutritional component in capsules as a food additive;

 [10] 2 - Taken in oral capsules or granules for medical use to treat liver disease, heart disease, fight against cholesterol, triglycerides, hormone replacement, headache and menopausal disorder, therefore their uses are not scientifically recognized;

 [11] 3 - Commercial use as an emulsifying food additive, one tablespoon equivalent of an egg, mixed with foods such as cake, chocolate, bread, margarine, salad, mayonnaise, ice cream, sausage, vitamin and others;

 [12] 4 - Diluted in saline for medical purposes for gene and vaccine transport or prolonged release medicinal products (cytostatic, cytotoxic and antibiotic);

 [13] 5 - The loaded liposome solution is used for radiological diagnosis;

 [14] 6 - In aesthetics, combined in creams and gel, therefore the use of "Npostabil" ampoules for intra- or subcutaneous injections is prohibited in Brazil.

 [15] Critiques and comments on current use of phosfolioidia and its solutions:

[16] 1 - Intravascular drug transport means: Drug-loaded liposomes and micelles reaching or not reaching their target sites do not perform prolonged release of the loaded, stabilized, and protected drugs in the liposomes, as claimed. , because of their rapid elimination in blood serum that will be absorbed into the blood vessels. mononuclear macrophages or opsonins, limiting their desired effects and serving only as a transport medium in the macrophages to be accumulated and disassembled in the liver, where they will be metabolized taking advantage only of the effects of fractional phospholipid formulas limiting the desired site effect. target.

 [17] 2- Intravascularly applied liposomes and micelles may cause transient blood lubrication increasing the risk of bleeding and possibly embolism or thrombosis;

 [18] 3- Means of oral drug transport: loaded liposomes, used as carriers and protectors, with drugs perform their functions only until they reach the stomach (because of contact with the gastric juice that has the acid). where they will be esterified, because contact with ions causes the collapse of the double layer of liposomes that will be disassembled into hydrophobic and hydrophilic segments to be metabolized in the digestive process by specific enzymes in the intestine;

[19] 4 - Taken in capsules as oral food substitutes: Cell membrane phospholipids ingested in larger quantities will be esterified in contact with gastric juice (hydrochloric acid) and the excess of them will be diluted in the remaining gastric solution to form. the liposomes and micelles, where they come in contact with the gastric mucosa and the food fragments. Therefore, they temporarily release their biological effects from opsonization by sticking to the corpses of the abrasive mucosa of the stomach and food fragments, in addition to tensor-active neurological induction (releasing acetylcholine) that irritates the gastric and intestinal mucosa and causes diarrhea, consequently these joint activities prolong natural digestive functions and may cause prolonged use;

 [20] 5 - Phospholipids or their solid fractions may cause allergies: taken orally or added to creams or gel for aesthetic use;

 [21] 6 - Side effects of subcutaneous injectable use in the fat layer of the phospholipid solution (lipostabil) have been described: pain, inflammation, jaundice, bruising, mucosal ulceration, sweating, gastrointestinal disorder, diarrhea, and overdose use in animals it can cause death. It is known that defense in the body does not accept free tissue substances without physiologically and anatomically unintegrated protections. Injection of the cell membrane phospholipid solution into the interstitium of healthy organs in the body causes a forced separation in the tissue cells (disintegrations) that will be marked by the phospholipid solution, signaling undesirable pathological effects, enabling the passage of the immune response and macrophages against the action of the phospholipid solution in the interstitium on healthy cells that are no longer protected from each other, consequently presented to opsonins, macrophages and the immune response. This explains their side effects and the results are in accordance with the order of immune defense,

[22] 7 - Positive effects of oral phospholipids are linked to their post-digestion fragments such as choline, carotid noids, phospholipid fractions to regenerate the cell membrane, phosphatidic acids, acetylcholine and others.

 [23] DETAILED DESCRIPTION OF THE INVENTION - Due to the circumstances described above, the biological normalizer object of the present invention has been developed.

 [24] Observations and General Explanations of the Biological Normalizer: The inventor's assessments are based on analytical studies of scientific publications, comparisons, and observations in clinical practice.

 [25] Liposomes and micelles can be formed only in vitro (physical process) and are not in such form in vivo. The appropriate environment for the functioning of liposomes and micelles is aqueous medium, saline (even in the presence of ions) and in contact with serosa (which resembles aqueous medium), where liposomes and micelles are stabilized between themselves and do not allow water to penetrate them. The organism has the ability to cope with and cure its own acquired diseases and to regularize its vital processes. These capabilities reinforce their effectiveness when potentiated by liposomes and micelles in solution, especially for external use.

[26] Liposomes and micelles in solution belong, when applied, to the nonspecific immune system by adhering to opsonins, microorganisms, and particles of pathological or mutant (physiologically and anatomically) unprotected formations in the body, activating the Complement System (SC), facilitating phagocyte functions and indirectly inducing their multiplication, while they will not be eliminated from macrophages or serological biological material. Liposomes and micelles in solution have very broad ionic, protein and lipophilic affinities, reflected in the formations of all the different and specific cell variations present in organisms, in which they explain their multiple properties needed when integrated into the organism.

 [27] Liposomes and micelles in a solution for external use are used as adjunctive monotherapy in vital organ processes and occasionally in combination with other appropriate non-aggressive biological medications indicated as the conditions that should be treated. For example, in the treatment of acne add to the solution of liposomes and micelles vitamin A.

[28] The immune system is responsible for curing the pathological effects of any genesis on the body in general or localized, as evidenced by the survival of the species. But for certain reasons, it cannot always cure disease and as a result chronic, autoimmune or other diseases result. The liposome and micelle solution acts in a similar way as leukocytes, penetrating pathological or withered tissue, advancing along marked pathways (not chemotaxis) by pathological effects without affecting integrated and protected cells at their specific tissue links, marking or They cover unprotected antigens or cell membrane antibodies by adherence, thus acquiring the appearance of liposomes and will be eliminated by mononuclear macrophages. Thus, macrophage phagocytosis is induced an important additional task against pathological and mutant factors in parallel to the activity of the specific immune system, which gives the liposome and micelle solution special importance as an auxiliary and complementary adjuvant to enhance the immune defense in healing and normalize the physiological state in the organism. Even though it cannot activate one type of immune system against two pathologies at the same time, therefore the liposome and micelle solution helps to circumvent this limitation of the immune system by enhancing nonspecific immune defense and enabling the body to perform more cu - various diseases, including some of which are considered incurable in current conventional medicine.

 [29] Micelles overcome the biological effects of liposomes and together in solution facilitate and activate the regulatory functions of the nervous system by performing responses from potentiated functional systems that are capable of curing 80% or more of the diseases that can be recognized by immune system such as antigens, pathological effects or physiologically and anatomically non-integrated materials in the body in external use. Some examples of using the aqueous solution of liposomes and micelles would be to help: trivialize or neutralize aggressive effects of topically applied substances; dispense with tissue transplantation needs; rechanging plugged vessels and activating circulation in artery pathological sites; act against pain; neutralize toxins of various genesis (chemical, physical and biological); and normalize, regenerate, recover central or peripheral neurological disorders including psychological disorders.

[30] Erythrocytes are neutral cells without nuclei, but are not free of specific homopotent markers in their membranes allowing, in vitro, unstable and temporary bonding of liposomes and micelles to them and to plasma fibrins that significantly prolong blood clotting time.

 [31] Cell membrane phospholipid solution has three types of effects that can be exploited:

[32] 1) Peripheral and central neurological effects: Liposomes and micelles in aqueous solution applied to the dermis have no biological affinities that allow them to penetrate transcutaneously or into physiological tissues, but have similar emulgent properties as soap or detergent. which softens the superficial structures of the skin. When the skin shows pathological signs, such as increased temperature in the region from external or internal pathological activities, wounds, inflammation, dry or scaly skin or any pathological change in the epidermis, the liposomes and micelles in solution penetrate in the area of woven tissue attachment in the outer layer of the dermis, reach the sensory bodies located in the cutaneous branch of the ascending nerves, induce a positive or negative charge of a potent neutral signaling effect, act as a neurological inducer to the system. central nervous system resembles acetylcholine in the nerves and activates the brain, which in turn potentiates the functional (belonging) systems in the organism. Peripheral neurological induction activates the belonging nervous center that responds with adequate functional regulations in the affected area of pathology to normalize and cure it; The central response to the induction of sensory bodies includes the other internal visceral branches of the same nerve. Are observed in practice immediate positive effects or within a few seconds of application of the solution, which indicates a nonspecific neurological induction in the peripheral parts of the ascending nerves followed by a regulatory response of the brain, including the cutaneous and visceral branches of the nerve.

 [33] 2 - Effects of oosonization: Liposome and mouse solution have, in part, properties of nonspecific opsonins by sticking to physiologically and anatomically unintegrated particles or in contact with the dermis surface (cleansing) or intravascuated use. - home, independent of natural body symbiosis, to be offered to macrophages and eliminated; It belongs to the unspecified innate defense of a broad functional spectrum facilitating phagocytosis, similar to the functions of serological opsonin, and assisting in normalization and complete cleansing of the treated area or tissue; On the pathological surface of the affected dermis, the liposomes and micelles develop their positive functions for a long time due to their mononuclear macrophage elimination.

[34] 3- Effects on visceral or internal pathologies: The solution of liposomes and micelles, preferably a solution enriched in micelles and smaller liposomes, to enhance external (topical) neurological induction in the treatment of internal or tissue pathological disorders. as explained in item 1 above. In addition to the prescribed neurological effects, liposomes and especially micelles can reach internal organs through: inhalation to penetrate to the left side of the heart through the pulmonary veins following the aorta toward the entire body; and intravenous applications or in venous vessel-rich regions as rectal applications to reach the large intestine, sigmoid and rectum where the solution penetrates the venous vessels (functional and private), by which all tissue and visceral activities in the urogenital region, liver and right side of the heart are controlled. dog.

 [35] Substances used in the products of this patent application: Cell membrane phospholipid solutions or their natural or synthetic fractions (separated, together or in combinations) form the liposomes and micelles in aqueous solution (preferably deionized). ) or in saline for external use. Occasionally, as indicated, hydrophilic, lipophilic substances, hormones or other useful nonaggressive biological substances are added. The naturally formed phospholipid solution has more larger liposomes that will first be eliminated, in decreasing bulk, from macrophages and opsonins, thus enabling smaller liposomes and micelles to perform their biological activities for a larger temporary space and especially when the solution It is added to another potentiated solution with small liposomes and microwaves in the microwave. It is noteworthy that these types of liposome and micelle solutions, even of natural origin, are not found in these formations in living beings or in natural forms in nature. They are products of human manipulation, resulting, therefore, from inventive activity, they constitute totally new processes, which provide significant functional improvements compared to what exists in the market.

[36] Forms of product applications of this patent application: Use only liposome and micelle solutions for external use (MU): Topic "wide or systematic" with pathological symptoms. In cavities covered with serous, mucous or abrasive tissues; pathological (visceral or tissue) body cavities (eg, phlegm and osteomyelitis); inhalation; oral and dental; and; intimate and general hygiene. In the form of drops: otological (even when tympanic membrane perforation); nasal; ophthalmic eye drops in various conditions (even in the perforation of the eyeball). In the form of solutions applied by a suitable catheter: rectally; genitourinary cavities; intramammary applications for veterinary use. And in intravascular injectable use. They are not used for internal (enteral) use.

 [37] Formulations: Substances used for external use only must be sterilized, pasteurized or in acceptable forms. Preferably use pure deionized water or saline in aqueous solutions for topical or external uses; and saline in uses: intravascular (external):

 [38] Solution - I: (Standard solution) Cell membrane phospholipids or their natural or synthetic fractions diluted in water or saline form liposomes and micelles in a ratio of 0.01 to 10.00 grams of phospholipids in 1 liter. of diluent.

 [39] For the purpose of this report natural phospholipid moieties are understood to be phosphatidylethanolamine, phosphatidylcholine, styromyelin, phosphatidylserine and phosphatidylinositol. Example: 5.00g in total of natural phospholipids.

[40] Synthetic fractions of phospholipids are understood to be the same as those created or manufactured in the laboratory as pure substances. Example: 5.00g of synthetic phospholipids.

 [41] Solution 1: The process for obtaining Solution 1 thus comprises dissolving 0.01 to 10.00 g of cell membrane phospholipids in one liter of diluent to form 0.01 to 10, 00g of liposomes and micelles. It is important to clarify that diluting the phospholipids in diluent in defined concentrations only forms a solution of liposomes and micelles in amounts that correspond to the weight of phospholipids used, but the numbers, the weights formed, the quantitative properties of the diluent cannot be defined. formed in the liposome lumen or the quantitative percentages formed between the liposomes and micelles in the defined solutions due to their very varied natural hydrophilic physical properties.

 [42] Solution - 2: Enrich Solution -1 only on smaller micelles and liposomes using microwaves. It is worth clarifying that the quantitative enrichment of liposomes or micelles of any origin or method used is a "blind" quantitative enrichment with the aim of enhancing their biological properties cited above. There are works that try to manipulate and adapt the liposomes according to their desired desires as a means of transport and do not value the micelles for lack of space to be loaded. Therefore, these works do not relate to the subject matter of the patent application.

[43] Process for obtaining Solution 2. Consisting of Solution 1, rich in micelles and smaller liposomes: This process is comprised of: providing a portion of Solution (1); step of submitting the cell membrane phospholipid solution (1) the microwave action that causes adequate waves with the molecular size of the water (resonance effect) causing vibrations in the water molecules that are found in and outside the liposome lumen, as well as the same process in the head. Bipolar amphipathic in the bilayer of the phospholipids that form the liposomes and in the outer layer of the micelles causing, in part, their destruction or fragmentation in decreasing proportion to the intensity and time applied to the microwave. Destroyed or fragmented formations spontaneously reconstitute into smaller forms to obtain a solution rich in micelles and smaller liposomes in the range of 0.001% to 1.00% of the total mass of the solution constituting solution rich in micelles and smaller liposomes. Values for laboratory microwave ovens Voltage (127V) are: mains frequency (60 Hz), operating frequency (2450MHz), usable power - microwave (900W), microwave mode power (1400W) require 10 seconds to 1 minute per liter; these values are not constant and may change, it is important that the temperature of the aqueous solution is preferably below 45 degrees Celsius. In the industrial market there are microwave ovens of all kinds, and manufacturers offer to build ovens as desired. It is worth clarifying that there is not only a solution of liposomes or micelles, they are always present together in the solution. The microwave only enriches the solution in smaller and smaller liposomes at the cost of the larger liposomes without defining the concentration or percentage of each, as the importance of this process in this patent application would be to increase the power of the solution any value to prolong the time of its elimination in the body. The results form smaller liposomes and additional micelles of varying sizes, because phospholipids, as they are known, spontaneously form liposomes and micelles in any solution, in this case the aqueous one. It is not possible to form a solution with 100% concentration in micelles or liposomes due to lack of diluent.

 [44] Solution - 3: To form liposomes and micelles adhered to lipophilic, hydrophilic or hormonal substances, the substance that should be added to solution-1 is mixed until a homogeneous solution is obtained, without the use of micro- wave, as indicated by the Therapeutic Indication, of very low molecular level concentrations in small IU (International Unit) or in a ratio of 0.002g to 0.2g of added substances. Liposomes and micelles spontaneously adhere to added useful substances.

[45] Process for obtaining Solution 3 consisting of liposomes and micelles added to biological substances: This process therefore comprises the step of providing a 1 liter portion of Solution -1 formed of liposomes and micelles in a ratio of 0.001% to 1.00% (rounded values) of the total solution mass and a portion of biological substances comprised of lipophilic, hydrophilic or hormonal substances according to the therapeutic indication to be met 0.0002% to 0.02% (rounded values) total mass of solution; mixing step to form a homogeneous solution of micelles and liposomes with the lipophilic, hydrophilic or hormonal biological substances constituting Solution 3. It is clear that the state of the art liposomes with internal or external intravascular medicinal products for use as a possibly patented carrier. However, in the present application it is to be understood that the addition of any substance to the phospholipid solution is only used as a diluent for the substance (not intra-liposomal transport), in order to be potentiated and applied topically as The added substances adhere spontaneously by opsonization to the liposomes and micelles already present in the solution, and are thus in accordance with the target results of this patent application, with enhancer or normalizer function. Adding substances to the liposome and micelle solution for topical or external use quantitatively decreases the high dosage of substances used in current medicine, as well as enhancing the healing response. For example: adding vitamin-A to the standard solution (solution-1) at a low concentration of 5000 IU to 15000 IU in one liter of thin-layer topical aqueous diluent as a moisturizer or acne treatment, thus enabling discontinue other ineffective treatments until the use of very aggressive oral or topical retinoic acid (in conventional medicine, normal daily oral doses of vitamin A for adults range from 30000 IU to 50000 IU per day).

 [46] Patent Application Products - Products obtained with the patent application biological normalizer are:

[47] 1. The solution -1 product is for external use and applied to moisten, immerse or bathe the treated area to humans and animals over the nerve branch dermis area. topography or the topography of the visceral epidermal pathology that should be treated. It serves to clean and enhance the pathological recoveries of functional systems in the organism of the treated area. The product is, therefore, a cleanser and enhancer of pathological recoveries of functional systems in the body from treated area for topical or external use, composed by aqueous solution of liposomes and micelles of cell membrane phospholipids or their natural fractions. 0.01 to 10.00 grams in 1 liter of diluent, consisting of sterile deionized pure water, or acceptable for topical or external use in the range of 0.001% to 1.00% rounded) of the total mass of the aqueous solution; said saline for intravascular and external use in the proportion of 0.10% to 10.09% (rounded values) of the total saline mass.

[48] 2 - The product resulting from solution - 1 and solution - 2, rich in micelles and smaller liposomes, is for external use and for general or selected intravascular injection to enhance unspecified immunological defense in the fight against infections or body pathologies, for example: embolism, necrosis, systematic and other diseases. Therefore, the product is a solution for topical use or a general or selected intravascular injection to enhance the non-specific immune defenses to fight infections or body pathologies, composed of physiological aqueous solution of liposomes and micelles. phospholipids of the cell membrane or their natural or synthetic fractions, in the ratio 0.01 to 10.00 grams in 1 liter of diluent, which consists of saline in the proportion of 0.001% to 0.99% (rounded) of phospholipids from the sa total saline solution; or said product is comprised of aqueous solution rich in smaller liposomes and micelles of cell membrane phospholipids or their natural or synthetic fractions, in the proportion of 0.01 to 10.00 grams in 1 liter of diluent, which consists of pure water. deionized so-called micelle-rich minor liposome-2 solution predicted to range from 0.001% to 1.00% (rounded values) of the total aqueous solution mass (for topical use).

[49] 3 - The resulting solution-2 product enriched in mouse and smaller liposomes mixed with solution-3 formed from solution-1 with non-aggressive biological substances to obtain a topical external product. Thus, the acquired product has two properties: it further enhances the non-specific immune system belonging to the micelles and smaller liposomes; and carries the useful medicines or biological substances diluted in solution in the treatment of diseases of living things. Thus, the product obtained is therefore a nonspecific immune system enhancer; and carrier of useful biologicals or medicaments consisting of aqueous solution of cell membrane phospholipids liposomes and micelles or their natural or synthetic fractions, in the ratio 0.01 to 10.00 grams of posfolipids in 1 liter of diluent, it consists of deionized pure water, distilled or acceptable said solution comprised in the ratio of 0.001% to 1.00% (rounded values) phospholipids of the total mass of the aqueous solution, and said physiological solution in proportion. 0.001% to 0.99% (rounded) phospholipids that formed the micelles and liposomes including the smallest of the total mass of physiological solution; and by aqueous solution with micelles and liposomes adhered to useful lipophilic, hydrophilic or hormonal biological substances in the ratio of 0.002% to 1.09% (rounded values) of the mixture of solutions 2 and 3 of the total mass of the aqueous solution, and by saline in the proportion 0.10% to 10.18% (rounded) of the mixture of solutions 2 and 3 of the total physiological solution mass.

 [50] 4- The product of the solution - 3 liposomes and micelles adhered to lipophilic, hydrophilic or hormonal biological substances potentiates the body's functional process for pathology normalization, avoids and eliminates side effects. The products purchased are for external and topical use. Thus, the product is therefore a potentiator of pathology normalization, composed of aqueous solution of cell membrane phospholipids liposomes and micelles or their natural or synthetic fractions, in the proportion of 0.01 to 10.00 grams. of phospholipids in 1 liter of diluent, consisting of sterile or acceptable deionized pure water, said solution in the ratio of 0,001% to 1,00% (rounded values) of aqueous solution or in the proportion of saline 0,001 % to 0.99% (rounded) phospholipids of the total physiological solution mass; said aqueous solution with liposomes and micelles adhered to useful lipophilic, hydrophilic or hormonal biological substances in a proportion of 0.01% to 10.02% (rounded values) of the total mass of the loaded aqueous solution-3 and by saline 0.01% to 10.02% (rounded) of the total mass of the loaded physiological solution-3.

[51] 5 - Solution -1 or solution - 2 (using standard saline). diluent) prolongs, in Vitro, blood clotting which can be used for laboratory purposes. The product is therefore comprised of an In Vitro coagulation extender comprised of Solution 1 or Solution 2.

 [52] External liposome and micelle solutions can be used at all ages (from newborn to very advanced ages) and in pregnancy; The treatment can be done anywhere, have no side effects; and do not create bacterial resistance.

 [53] Contraindications for solutions are very limited: inhalation in case of asthma or shortness of breath; interstitial application of physiological tissues.

[54] Abstract: The most important function of the liposome and micelle solution is its external use because of neurological induction and opsonization that potentiate the long-term vital organ functions in the body based on the biological properties of liposomes and micelles. Micelles have more potent biological effects than liposomes, and together they potentiate biological properties pertaining to nonspecific immune defense and functional activities in the body until they are eliminated from the nonspecific immune system itself such as opsonins and of macrophages. Neurological induction enhances in the brain a reinforced regenerative and regulatory response of curative topical and visceral effects, acting as a surface cleanser for "opsonization effect" and helping to normalize physiologically and biologically unintegrated areas. These properties give the solution a new functional name of: "Normalization". Biological ".

 [55] The information below concerns the storage procedures and packaging for the biological standardizer:

 [56] The shelf life of products has different acceptable timeframes, depending on their preservation forms as practiced in the pharmaceutical market.

 [57] Products with liposomes not loaded with medicines or biological substances, hermetically sealed in a cool place, are valid for 1 year.

 [58] Products with liposomes not loaded with hermetically sealed medicines or biological substances stored in the refrigerator at temperatures of 3 to 10 degrees Celsius are valid for 3 years.

 [59] Products containing liposomes loaded with medicines or biological substances in dark, hermetically sealed containers stored in the refrigerator at temperatures of 3 to 10 degrees Celsius are valid for 1 year.

 [60] Products with liposomes not loaded with medicines or biological substances stored in tightly sealed packages and frozen at temperatures from -10 ° C or below are valid for 5 years.

 [61] Products containing medicinal or biologically loaded liposomes stored in hermetically sealed, dark packings and frozen at temperatures from -10 degrees Celsius or less are valid for 3 years.

[62] An indication for use is to shake the products before use for liposome reconstruction. [63] Products in use (after opening) have a shelf life of 40 days in a cool place or refrigerator.

[64] Forms of presentation of the products: Packages may be offered in bottles of useful contents ranging from: 10 ml for eye drops; 20 ml for ear drops; 15 ml for rectal use; 50 ml for topical areato use; 150 ml for systematic topical use and for use in rectal or urogenital lavage; and specific kits ready to facilitate different uses of the products.

[65] 30 ml pack for intramammary use in dairy cows (veterinary product).

Claims

 1) “BIOLOGICAL NORMALIZER”, characterized by Solution 1 comprising solution of cell membrane phospholipid liposomes and micelles in the ratio 0.01 g to 10.00 g in one liter of diluent; Said Solution 1 pure or in association with useful biological substance (s) and / or medicinal product (s).  2. "BIOLOGICAL NORMALIZER" according to claim 1, characterized by liposomes and micelles belonging to integral cell membrane phospholipids or natural or synthetic fractions of phospholipids.  3. "BIOLOGICAL NORMALIZER" according to Claim 1 or 2, characterized by a diluent comprising deionized, pasteurized, distilled or acceptable pure water.  4. "BIOLOGICAL NORMALIZER" according to claim 1 or 2, characterized by a diluent comprising physiological saline.  5. "BIOLOGICAL NORMALIZER" according to claims 1 or 2 or 3 or 4, characterized by Solution 2 rich in mice and smaller liposomes, comprising a portion of Solution 1, comprising 0.01 g to 10.00 g. micelles and liposomes in one liter of diluent; said smaller micelle and liposome-rich aqueous solution predicted to range from 0.001% to 1.00% (rounded values) of the total mass of the solution. 6. "BIOLOGICAL NORMALIZER" according to Claim 5, characterized in that Solution 2 rich in micelles and liposomes smaller than 20 to 3500 pm (micrometer), comprising a portion of Solution 2 rich in micelles and smaller liposomes in proportion. from 0.01 g to 10.00 g in one liter of diluent; Said Solution 2 rich with micelles and smaller liposomes predicted at a ratio of 0.001% to 1.00% (rounded values) of the total mass of the solution.  7. "BIOLOGICAL NORMALIZER" according to claim 1 or 2 or 3 or 4, characterized by Solution 3 with liposomes and micelles adhering to useful biological substances; Said Solution 3 comprised per portion of Solution 1 and per portion of useful biological substances comprised of hydrophilic, lipophilic, hormones; said adhered liposomes and micelles predicted in the ratio of 0.01 g to 10.00 g in one liter of diluent; Said Solution 1 predicted to be from 0.001% to 1.00% (rounded values) of the total mass of the solution and adhered to biological substances provided at a ratio of 0.01019% to 10.0197% (rounded values) to the total mass of the solution .  8. A "BIOLOGICAL NORMALIZER PROCESS" for obtaining the biological normalizer of claims 1 to 7, characterized in that it provides Solution 1 and comprises: step of providing 0.01 g to 10 g of cell membrane phospholipid solution; step of diluting cell membrane phospholipids in one liter of diluent to obtain aqueous solution of liposomes and micelles in the ratio of 0.01 g to 10.00 g per liter of diluent; and by step of whether or not to add useful biological substance (s) and / or medicinal product (s) for external use. A "BIOLOGICAL NORMALIZER PROCESS" according to claim 8 characterized by liposomes and micelles belonging to integral cell membrane phospholipids or to natural or synthetic fractions of phospholipids. 10. "BIOLOGICAL STANDARD OBTAINING PROCESS" according to claim 8 or 9, characterized by diluent comprising deionized, pasteurized, distilled or acceptable pure water.  1. A "BIOLOGICAL NORMALIZER PROCEDURE" according to claim 8 or 9, characterized by diluent comprised of saline.  12. "BIOLOGICAL STANDARD OBTAINING PROCESS" according to claim 8 or 9 or 10 or 11, characterized in that it provides Solution 3 with liposomes and micelles adhered to useful biological substances and comprised: by the step of providing a portion of Solution 1 and a portion of useful biological substances comprised of hydrophilic, lipophilic, hormones; Said Solution 1 in the ratio of 0.001% to 1.00% phospholipids (rounded values) of the total mass of the solution and the useful biological substances in the ratio of 0.0002% to 0.02% (rounded values) of the total mass of the solution. ; by step of mixing Solution 1 with useful biological substances sufficiently to obtain a homogeneous solution and by step of obtaining liposomes and micelles adhered to hydrophilic, lipophilic, hormone biological substances. 13. "BIOLOGICAL STANDARD OBTAINING PROCESS" according to claim 8 or 9 or 10 or 11, characterized in that it obtains Solution 3 with liposomes and micelles adhered to external use medicine and comprised: by step providing a portion of Solution 1 and a portion of medicament; Said Solution 1 in the ratio of 0.001% to 1.00% (rounded values) of mass total solution and drug portion in the ratio 0.0002% to 0.02% (rounded values) of the total solution mass; step of mixing Solution 1 with the medicament portion until a homogeneous solution is obtained; and by stage of obtaining liposomes and micelles adhered to external medicine. 14) "PRODUCT OBTAINED FROM THE BIOLOGICAL NORMALIZER" of claims 1 to 13, characterized by enhancer of pathological recoveries of functional systems in the organism of the treated area of topical use, composed by Solution 1 comprised of aqueous solution of phospholipid liposomes and micelles of the cell membrane or its natural or synthetic fractions, in the proportion of 0,01 to 10,00 grams in 1 liter of diluent, consisting of pure, deionized, distilled, sterilized, saline or otherwise acceptable water for external use .  15. "BIOLOGICAL NORMALIZER PRODUCT" according to any one of claims 1 to 13, characterized by external use including intravascular injection to enhance nonspecific immune defense against infection or body pathology, and to extend the time of liposome elimination and micelles in the solution 1 organism in the proportion of 50% of the total mass of the solution; and by Solution 2 rich in smaller micelles and liposomes predicted at 50% of the total mass of the solution. 16) "PRODUCT OBTAINED FROM THE BIOLOGICAL NORMALIZER" of claims 1 to 13, characterized by a non-specific immune system enhancer; and carrier of useful drugs or biological substances, composed of aqueous solution 2 rich in micelles and smaller liposomes, comprised of Solution 1 enriched with micelles and smaller liposomes; Said Solution 2 provides for a ratio of 0.001% to 1.00% (rounded values) of the total mass; and by aqueous solution 3 with liposomes and micelles adhered to useful lipophilic, hydrophilic or hormonal biological substances in the ratio of 0.002% to 1.09% (rounded values) of the total mass of the solution.  17) "PRODUCT OBTAINED FROM THE BIOLOGICAL NORMALIZER" according to any one of claims 1 to 13, characterized by a pathology normalization enhancer consisting of Solution 1 in the ratio of 0.001% to 1.00% (rounded values) of the total mass. such a solution; and by useful lipophilic, hydrophilic or hormonal biological substances adhered to liposomes and micelles constituting solution 3 in the proportion of 0.01% to 10.02% (rounded values) of the total mass of the solution.  A product obtained from the BIOLOGICAL NORMALIZER ”of claims 1 to 13, characterized by an In Vitro coagulation extender comprised of Solution 1 or Solution 2 useful in the laboratory, said Solution 2 comprised of Solution 1 enriched with micelles and liposomes. smaller ones.