WO2018191801A1 - Method for producing a fibrin biopolymer, means for applying said fibrin biopolymer and method for applying said fibrin biopolymer - Google Patents

Abstract

A method for producing a fibrin biopolymer, means for applying said fibrin biopolymer, and a method for applying said fibrin biopolymer, according to which dehydration and grinding of biopolymer components (serine protease purified from serpent venom and cryoprecipitate rich in fibrinogen extracted from large animals) is predicted, resulting in the production of two powder components, the properties of which remain unaltered for a long period of time, without the need for freezing; said two powder components are provided separately, or are mixed together and impregnated on a supporting element, or only one of them is impregnated on a supporting element, or, even, only one of them is mixed with a substance which gives it consistency; suitable application means are provided, which involve providing a diluent liquid, stored separately or mixed with one of the powdered components.

Description

 "PROCESS FOR OBTAINING FIBRINE BIOPOLYMER, MEANS OF APPLYING SUCH FIBRINE BIOPOLYMER, AND PROCESS OF APPLYING FIBRINE BIOPOLYMER".

 TECHNICAL FIELD

 The present invention patent relates to a process for obtaining fibrin biopolymer, the means for applying said fibrin biopolymer, and the process for applying said fibrin biopolymer, which fibrin biopolymer presents, as Its primary characteristics are the fact that it is manufactured on an industrial scale, can be purchased commercially in pharmacies, without the need for a prescription, and can be applied topically by the user himself, outside hospital settings, without the presence of a specialized professional from the hospital. to be a final product, which is primarily an OTC (over-the-contain medicine), ie an over-the-counter medicine, subject to the limitation of registrations with each in each country), intended for the average consumer, employed to treat cuts, scrapes, wounds and bleeding in general, even those occurring during rurgies. Such fibrin biopolymer has its main components obtained exclusively from materials of animal origin, notably:. purified snake venom thrombin-like, or the same component synthesized in the laboratory; and //. fibrinogen-containing cryoprecipitate from large animals such as oxen and horses, and more particularly buffalo (buffalo).

DESCRIPTION OF TECHNICAL STATE

As is well known in the art, fibrin is a natural biopolymer that has characteristics of bioactivity, biocompatibility and biodegradability. Because they provide excellent tissue sealing and bonding properties, such fibrin biopolymers have been commonly called fibrin "sealants" or "glues".

More particularly, fibrin biopolymers obtained from human blood have also been known in the art for a long time. Said fibrin biopolymers are employed in surgical procedures in order to reduce bleeding and provide a firm adherence between tissues.

 [004] As is well known, the first research on fibrin biopolymers (or sealants or glues) dates from the 1940s, which consisted of fibrinogen and thrombin, both from humans.

 Since the 1970s, several new proposals for fibrin biopolymers have been developed, also involving the mixing of these two components (fibrinogen and thrombin), but only one of them continues to be extracted from humans (fibrinogen). , while human thrombin was replaced by bovine thrombin or snake venom purified thrombin.

[006] An example of such fibrin biopolymer is that described in BR PI 9103724-7, published 30/03/1993, concerning a "COBRA POIS DERIVATED FIBRIN ADHESIVE FOR PREPARATION". According to that proposal, the fibrin glue consisted of two solutions, one consisting of a fibrinogen-rich cryoprecipitate obtained from fresh human plasma, and the other consisting of a fraction of lyophilized snake venom.

Other examples of fibrin biopolymers already known in the art are those described in WO 2007/121748, published 11/01/2007, and US 9,446,166, published 7/24/2014.

As it turns out, in the fibrin biopolymers known in the art, one of the components of (the fibrinogen-containing cryoprecipitate) invariably comes from humans. In addition, in biopolymers For commercially approved fibrin for use, both components (human fibrinogen and thrombin) must be kept frozen at minus 20 ° C in order not to lose their properties, and at the time of biopolymer use they must be thawed and mixed.

 For the application of such biopolymers, applicator devices are also known in the art, formed either by two communicable chambers, or by two contiguous syringes, each comprising one of the biopolymer components, as well as by a mixing chamber capable of mix them when applying the biopolymers to the surface of the tissue or organ to be treated; Such devices also need to be stored in freezers to keep frozen components inside. Similarly, shortly before the biopolymer is applied, it is necessary to remove such devices from the freezer so that the components contained in their chambers or syringes are thawed, said devices being then employed to mix the components as well as to apply the biopolymer. newly formed on the surface of the site to be treated. Obviously, given the complexity of the application provided by these devices (by spraying with syringes and needles), these devices can only be handled by medical professionals (doctors or nurses) who are already used to operating surgical instruments.

On the other hand, methods for providing drugs and / or biopolymers by fluidization thereof are already known in the art. As is known, fluidization is the process by which solid particles are transformed into liquid state by suspending them in a gas or liquid. Thus, according to methods already developed, the fine particles of a drug and / or biopolymer are fluidized by a carrier gas (preferably carbon dioxide or nitrogen) or a solution. net any. For such, such components are injected into a microtube, where the powder and liquid or gas come into contact and are mixed. The resulting mixture is then sprayed from the tip of the microtube to the body site to be treated.

 Although such a fluidization method has been attempted to provide fibrin biopolymer, this has never been achieved in practice due to the aforementioned need for freezing of the components, and the fact that the reconstituted and fluidized material, formed by mixing a fibrinogen and a thrombin, it forms a clot that eventually clogs the valve of conventional sprays.

Said fibrin biopolymers known in the art, being obtained from human blood, present a number of problems. One of them lies in the fact that human blood used in biopolymer production can contain contaminating factors, such as contagious viruses, among others, and can therefore be a potentially transmitting element of infectious diseases.

 [013] Another major drawback lies in the scarcity of the raw material needed to obtain those biopolymers, namely human blood. In fact, as is well known, in Brazil and in various countries of the world, the commercialization of human blood is prohibited, which, therefore, can only be obtained through the voluntary donation of people. Particularly in Brazil, the number of permanent donors is still very low, which means that blood bank stocks are always at very low levels.

Thus, with the constant lack of blood in the blood banks, there is a shortage of this raw material, essential for the manufacture of fibrin biopolymers. In some countries, the small amount of fibrin biopolymer that can be manufactured is only used in situations of extreme need, more specifically in so-called applications. "noble" (major surgeries, such as liver transplant surgeries and heart and brain surgeries, among others). Therefore, these major surgical procedures with the use of fibrin biopolymer, even abroad, happen only in specific situations of use, and in Brazil, the use of fibrin biopolymers in many of these surgeries is avoided, since it requires importation of fibrin biopolymer manufactured in other countries at a substantially high cost.

[015] As it turns out, fibrin biopolymers are an expensive and scarce product that is handcrafted within laboratories on a very small scale, and which can be used only and only in hospital settings by skilled professionals in the field. doctor. Currently, this production only occurs in laboratories abroad, there is no production by the Brazilian national industry.

[016] For all these reasons, fibrin biopolymers to date have never been able to be an industrialized product, available to the end consumer, and can be purchased as an over the counter (OTC) product, ie a product that could be purchased at points of sale (pharmacies and drugstores), without the need for medical prescription, or even prescription, but directly by the end consumer.

[017] As mentioned above, fibrin biopolymers, because they are an extremely expensive and scarce product, are only available between the walls of hospital and university laboratories (and only produced abroad), where they are kept frozen, and only They are used when needed in major surgeries, in the hospital environment, where they are thawed shortly before their application by doctors or nurses during surgery.

More recently, an innovative fibrin biopolymer has been developed, in which not only thrombin but also fibrinogen has become of animal origin. Such fibrin biopolymer is described in document BR 10 2014 011436-0, published on 23/02/2016, referring to a "FIBRINE SEALANT FOR TOPICAL USE, METHOD OF FORMATION AND USE".

 According to that document, the fibrin sealant provided therein is comprised of a serinoprotease purified from snake venom, a fibrinogen-rich cryoprecipitate extracted from large animals, preferably buffalo (buffalo), and a diluent. configured by calcium chloride. Such components are kept separately in individual vials, which need to be contained inside freezers, so that their contents are kept frozen at minus 20 ° C until use, without which the properties of the components are completely compromised.

 [020] Only at the time of use are such vials removed from the freezer and kept at room temperature (between 15 and 25 ° C) for 10 to 20 minutes to thaw the components contained therein.

 Once thawed, the diluent is first injected into the vial containing serinoprotease and shaken and set aside. Using a syringe and needle, the whole contents of this vial (diluted serinoprotease) are aspirated. With another syringe and needle, aspirate the entire contents of the vial containing the cryoprecipitate. Topical application of the two components is then performed, with the two syringes in parallel and their respective bevels directed to the site to be treated, said components being polymerized "in situ" after being properly mixed.

[022] As it no longer contains any components from human blood and is now exclusively of animal origin, the fibrin sealant described in that application BR 10 2014 011436-0 presents no risk of transmission of blood-borne diseases. eliminating the disadvantage of conventional fibrin biopolymers as potential transmitters of infectious diseases.

[023] In addition, by ceasing to use the component extracted from human blood, which was replaced by a component extracted from the blood of animals (buffalo, or buffalo), the once scarce and expensive raw material made It is now abundant and inexpensive, enabling the eventual manufacture of fibrin biopolymer on a large scale.

 Additionally, the predicted fibrin sealant described in BR 10 2014 011436-0 has a highly coagulant effect, capable of clogging blood vessels, and thus stopping bleeding immediately, and still creates a transparent film over the application site, which accelerates cell multiplication, facilitating tissue healing and recovery by stimulating the emergence of new blood vessels.

 However, despite the aforementioned advantages over conventional fibrin biopolymers, the fibrin sealant described in BR 10 2014 011436-0 continued to require that its components (serinoprotease purified from snake venom and fibrinogen-rich cryoprecipitate extracted from large animals) are kept frozen until use, thus continuing to limit the manufacture and use of the single biopolymer exclusively to hospital environments.

 [02 6] In addition, as the components must be mixed and applied at the time of use (through the use of needles and syringes), the use of this fibrin sealant continues to require the action of a healthcare professional. medical area, necessarily being preached by doctors or nurses, during the occurrence of surgeries.

[027] Accordingly, it has never been possible to supply the filament sealant provided for in that document BR 10 2014 01 1436-0 as a product. industrialized, large-scale, commercially available commercially available at the point of sale (pharmacies and drugstores) as an over-the-counter (OTC) product without the need for a prescription.

 [028] In view of all the above, it can be concluded that a fibrin biopolymer that has been supplied as a low-cost, industrialized finished product has not been developed to date, that could be purchased directly by the consumer at points of sale, without the need for a prescription (OTC product), and that could be used and applied by the consumer directly over the place of his or her body to be treated, outside hospital environments, and without the assistance of a medical professional.

OBJECTIVES OF THE INVENTION

 [029] Thinking precisely of obtaining a solution that could simultaneously meet all these needs, the Depositor began studies and research on the subject, in order to:

a) enable the manufacture of fibrin biopolymer in a way that does not require freezing, as hitherto required;

b) enable the supply of fibrin biopolymer in a way that would allow the end user to purchase this product at points of sale, and without the need for medical prescription, or even prescription, respecting local health legislation, but directly by consumer.

c) enable the application of fibrin biopolymer in a way that would allow topical use by the user himself, and no longer by a medical professional (doctor or nurse); and

d) make it possible to obtain an industrialized final product produced on a large scale and at a low cost.

[030] To achieve these objectives, the Depositor has created these new "PROCESS FOR OBTAINING FIBRINE BIOPOLYMER, MEANS OF APPLICATION OF SUCH FIBRINE BIOPOLYMER, AND APPLICATION PROCESS OF SUCH FIBRINE BIOPOLYMER", which are the subject-matter of this invention.

According to the present invention, the process of obtaining fibrin biopolymer now innovated provides for the dehydration and grinding of both components of the biopolymer, namely: /. serinoprotease purified from snake venom, or the use of this component from its synthesis in the laboratory, by methods known to science (produced by recombinant technology, in order to extract its active synthetic form, which is the from prokaryotic organisms, eg bacteria, or eukaryotes, eg fungi and yeast, or other methods for the same purpose); and //. fibrinogen-rich cryoprecipitate extracted from large animals (preferably buffalo, or buffalo); As a result, two powdery products are obtained, the properties of which are kept unchanged for a long time, thus eliminating the need for freezing. optionally and optionally, to these two powdery products, other components such as preservatives and stabilizers may be added to further enhance and ensure the maintenance of their biological properties.

[032] In a first embodiment, the two powdered products (fibrinogen-rich cryoprecipitate extracted from large animals and snake venom-purified serinoprotease) are supplied separately within their separate, watertight chambers arranged in a first The applicator means is now also innovated, and provision is made for the supply of a diluent liquid which is stored separately in another independent and watertight chamber also provided for in said applicator medium. [033] In this embodiment, when using the biopolymer to treat any wound, the two powdered products and the diluent liquid are properly mixed together to achieve the well-homogenized and polymerized wound in the form of a sealing film and which, arranged over the wound, stops bleeding almost immediately, and accelerates healing and tissue recovery.

[034] In a second embodiment, the two powder products (fibrinogen-rich cryoprecipitate extracted from large animals and snake venom-purified serinoprotease) are supplied properly mixed and impregnated with a support element provided in a second second. The applicator medium is now innovated, and it is also envisaged to provide a diluent liquid which is stored separately in an independent and watertight compartment provided for in said applicator medium.

 In a variation of this second embodiment, said support member is formed of only one of the two powdered products (the fibrinogen rich cryoprecipitate extracted from large animals), while the other powdered product (the purified serinoprotease from snake venom) is supplied diluted in the diluent liquid stored in said compartment provided for in the second applicator medium.

Thus, in both variations of this second embodiment, when using the biopolymer to treat any injury, the support member formed by one or both of the powder components receives respectively the diluent liquid provided or not the other powder component already diluted in it, and in both cases, the three products are properly mixed, also reaching the wound properly homogenized and polymerized, in the form of a same sealant and transparent film, which, arranged on the wound. stops bleeding almost immediately and accelerates healing and tissue recovery.

 [037] And in a third embodiment, one of the two said powdered products (the fibrinogen rich cryoprecipitate extracted from large animals) is mixed with a substance capable of giving it consistency (eg a collagen) so as to be provided in the form of a blade or sheet which itself constitutes a support element; the other powdered product (serinoprotease purified from snake venom) is mixed with a diluent liquid, said mixture being packaged within a watertight chamber provided in a usual spray bottle.

Thus, in this embodiment, when using the biopolymer to treat any wound, the powdered blade product is sprayed into the mixture in which the other powdered product is already diluted, the latter being diluted. three equally mixed products, reaching the wound properly homogenized and polymerized, and forming a same sealant and transparent film, which, arranged on the wound, stops bleeding almost immediately, and accelerates healing and tissue recovery.

Also according to the present invention there are provided means for applying the fibrin biopolymer resulting from this new process of obtaining. Such application means may be configured by a spray bottle, an adhesive bandage or a curative strip.

[040] In the first case, the spray bottle is internally provided with three independent chambers housing the two powder components and the diluent liquid respectively, a completely new arrangement compared to conventional spray bottles.

In the second case, the adhesive bandage is provided with a support element which is impregnated with one or both of the powdered components, which support element is surmounted by an independent and watertight compartment, which houses the diluent liquid, whether or not endowed. of a component powder already diluted therein, said compartment being provided with appropriate release means capable of releasing the outlet of the liquid contained therein; Such an arrangement is also totally innovative in relation to conventional adhesive bandages.

 [042] And in the third case, the curative strip is formed by a blade or sheet formed entirely by one of the powdered components (the fibrinogen-rich cryoprecipitate extracted from large animals), thanks to the mixture of a substance that gives it consistency (eg collagen) itself constituting a support element upon which a mixture containing the diluent liquid and the other diluted powder component (the purified serinoprotease purified from from snake venom); Such curative strip also features totally innovative disposition.

Also according to the present invention there is provided the application process of the fibrin biopolymer resulting from this new obtaining process, which application process provides for three sequence of procedures, depending on the applicator medium employed.

Thus, when using the first applicator medium (the new above-mentioned spray bottle), the two powder components and the diluent liquid contained in the three independent chamber chambers of the bottle are helically sprayed into the ambient air independently and concomitantly. at a predetermined distance from the surface of the wound to be treated, the three components being then properly mixed in the air during the course of that distance to achieve the already properly homogenized and polymerized wound in the form of the transparent, sealing film. mentioned above.

Already when using the second applicator means (the above mentioned new adhesive bandage), said bandage is fixed on the wound to be treated and the support element coincides with it. already impregnated with one or both powdered components; then, using the release means provided in the compartment arranged above the support element, the liquid contained therein is released onto said support, which liquid, respectively, is the diluent liquid provided with the other component. powder already diluted in it, or is the diluent liquid alone; Said liquid, when mixed with one or both of the powdered components already impregnated with the support element, also causes the same aforementioned transparent sealing film to form which is deposited on the wound.

 And when using the third applicator means (the aforementioned new curative strip), said strip is applied over the wound to be treated, which is formed by the blade integrally formed by one of the powdered components upon mixing. with a substance capable of giving it consistency (eg collagen); then, using a conventional spray bottle, the mixture of the diluent liquid into which the other powder component has already been diluted is sprayed on said blade, which mixture, in turn, when mixed with the component dusting of the blade also causes the same aforesaid transparent sealant film deposited on the wound.

 As it turns out, with the new processes for obtaining and applying fibrin biopolymer, as well as with the new applicators of said biopolymer, a fibrin biopolymer was obtained for the first time as a product. which may be manufactured on an industrial scale, which will be commercially available at points of sale (pharmacies and drugstores), and which may be purchased and used by the consumer himself, without the need for medical prescription, and without the presence of a specialized medical professional.

[048] This product, which, as already mentioned, may appear in the In the form of a spray bottle, in the form of an adhesive bandage or in the form of a bandage (accompanied by a conventional spray bottle), it can be applied to general injuries, from minor cuts resulting from simple domestic accidents (cuts with knives, razor blades, scratches, injuries from falls, etc.) to large wounds, being a highly effective product for stopping bleeding and accelerating tissue healing by stimulating the emergence of new blood vessels.

[049] In this way, with the process of obtaining, the application process and the means of application of the now innovated fibrin biopolymer, an innovative and revolutionary solution in the medical field has been achieved that meets all the requirements required for obtaining a patent: novelty, inventive activity and industrial application.

 [050] In fact, this new solution has been able to simultaneously meet all the needs of the current state of the art as it has enabled what has never been achieved before: the manufacture of a fibrin biopolymer as a product large-scale, low-cost, industrialized final product that no longer requires the freezing of its components, which can be purchased directly by the end-user at point of sale, without the need for a prescription, and which can be applied topically by the user himself, outside the hospital environment and without the need for a medical professional.

[051] For all these reasons, the processes and means now developed by the Depositor deserve the protection of an Invention patent.

DESCRIPTION OF DRAWINGS

In addition to the present description, in order to gain a better understanding of the characteristics of the subject matter of the patent, a set of drawings accompanies this report, in which, by way of example and not limitation, the following was represented: Figure 1 is a block diagram illustrating the steps of the process for obtaining the now-innovated fibrin biopolymer;

 Figures 2 and 3 are schematic illustrations of a first applicator medium of the fibrin biopolymer manufactured according to the obtaining process illustrated in Figure 1, showing it through longitudinal and transverse sections, respectively;

 Figures 4 and 5 are enlarged and equally schematic details of the applicator means illustrated in Figures 2 and 3;

 Figures 6, 7 and 8 are schematic illustrations of a second applicator medium of the fibrin biopolymer manufactured according to the procurement process shown in Figure 1, showing it through bottom view, side view and top view, respectively; and

 Figure 9 is a schematic illustration of a third applicator medium of fibrin biopolymer manufactured according to the procurement process shown in Figure 1, showing it through perspective.

 DETAILED DESCRIPTION OF THE INVENTION

 [053] This invention relates to a "FIBRINE BIOPOLYMER PROCESS", "MEANS OF APPLICATION OF THE FIBRIN BIOPOLYMER", and the "FIBRINE BIOPOLYMER APPLICATION PROCESS".

 According to the present invention, and as illustrated in the block diagram of Figure 1, the "BIOPOLYMER PROCESS OF

FIBRINA "now innovated consists of the following steps:

- Step 1: Dehydration and subsequent crushing of fibrinogen-rich cryoprecipitate extracted from large animals (preferably buffalo - buffalo) to give a first powder component whose properties are also kept unchanged for a long period of time, also dispensing with it. the need for freezing; - Step 2: Dehydration and subsequent grinding of purified serinoprotease from snake venom, or the use of the same component from its synthesis in the laboratory by methods known to science (produced by recombinant technology to extract its form). synthetic, active, being from prokaryotic organisms, eg bacteria, or eukaryotes, eg fungi and yeast, or other methods for the same purpose), so as to result in a second powder component whose properties are kept unchanged for a long time, eliminating the need for freezing;

 Step 3: Storing said first powder component obtained in Step 1 in an independent, watertight chamber;

 Step 4: storing said second powder component obtained in Step 2 in another independent, watertight chamber;

 - Step 5: Storage of a diluent liquid in another independent and watertight chamber;

 - Step 6: At the time of use, spraying and subsequent mixing between the two powder components and the diluent liquid respectively stored in Steps 3, 4 and 5, resulting in the homogenization and polymerization of the three components, resulting in a sealant film. and transparent, capable of stopping bleeding and accelerating healing and tissue recovery;

 - - as an alternative to Steps 3, 4 and 6:

 Step 7: Mixing said first and second powder components obtained respectively in Steps 1 and 2, and subsequent impregnating them to a support element;

- Step 8: at the time of use, release of the diluent liquid stored in Step 5 over the support element impregnated with the two powdered components obtained in Step 7, resulting in the homogenization and polymerization of the three components, also resulting in a clear, sealing film capable of stopping bleeding and accelerating tissue healing and recovery by stimulating the emergence of new blood vessels;

 - - as another alternative in place of Steps 3, 4 and 6, and Steps 7 and 8:

 Step 9: impregnating said first powder component obtained in Step 1 with a support element;

 Step 10: Mixing between the second powder component obtained in Step 2 and the diluent liquid stored in Step 5, and consequently storing this mixture in an independent, watertight chamber;

 - Step 11: At the time of use, release of the mixture (second powder component + diluent) stored in Step 10 on the support element impregnated with only one of the powder components obtained in Step 9, resulting in the homogenization and polymerization of the three. components, also resulting in a clear, sealing film capable of stopping bleeding and accelerating tissue healing and recovery by stimulating the emergence of new blood vessels;

 - - and as another alternative to Steps 3, 4 and 6, and Steps 7 to 11:

 Step 12: Mixing between the first powder component obtained in Step 1 and a substance capable of giving it consistency (eg collagen), resulting in a blade which itself constitutes a support element;

 Step 13: Mixing between the second powder component obtained in Step 2 and the diluent liquid stored in Step 5, and consequently storing this mixture in an independent, watertight chamber;

- Step 14: At the time of use, release of mixture (according to powder + diluent) stored in Step 13 on the support element configured by the first blade-shaped powder component obtained in Step 12, resulting in the homogenization and polymerization of the three components, also resulting in a clear, sealing film. , capable of stopping bleeding and accelerating tissue healing and recovery by stimulating the emergence of new blood vessels.

 [055] Dehydration of serinoprotease purified from snake venom and fibrinogen-rich cryoprecipitate extracted from large animals can be achieved by simple drying, hot air drying, filtration, mechanical pressing, osmotic dehydration, freeze drying (freezing followed by sublimation). ), or other methods.

[056] Grinding of serinoprotease purified from snake venom and fibrinogen-rich cryoprecipitate extracted from large animals can be achieved by milling, mechanical centrifugation, mechanical bombardment, or other methods.

 And preferably the diluent liquid contains in its composition calcium chloride.

 Also according to the present invention, the "FIBRINE BIOPOLYMER APPLICATION MEANS" resulting from the process described above can be configured by a spray bottle (15) (as schematically illustrated in Figures 2 to 5), by a adhesive bandage (16) (as shown schematically in Figures 6 to 8), or by a curative strip (17) (as shown schematically in Figure 9).

[059] In the first case (see Figures 2 to 5), the spray bottle (15) is internally provided with three independent, watertight chambers (15a) housing respectively the two powder components (serinoprotease purified from snake venom and cryoprecipitate rich in fibrinogen extracted from large animals) as well as the diluent liquid. From said chambers (15a), respective independent ducts (15b) depart, which, inside the spray nozzle (15c) of the vial (15), interconnect with respective also independent helical channels (15d), duly coiled together, ending in respective sprinkler nozzles (15e).

[060] In the second case (see Figures 6 to 8), the adhesive bandage (16) of any suitable shape (rectangular, square, circular, or other) is provided with an appropriate adhesive area, duly covered by one or more. protective strips (16a), which area surrounds a central support member (16b) (for example, a pad), which is impregnated with one or both of the powdered components (only fibrinogen-rich cryoprecipitate extracted from large animals, or this is serinoprotease purified from snake venom). Said central support member (16b) is provided with a separate, watertight compartment (16c) within which the diluent liquid is disposed, which may or may not be provided with the other diluted powder component therein (purified serinoprotease). from snake venom) said compartment (16c) being provided with appropriate release means (16d) which, when actuated, release the outlet of said liquid.

Preferably, said diluent liquid release means (16d) stored in said compartment (16c) is configured by a sealing seal that seals a predicted opening between said compartment (16c) and the support member (16b). which seal, when broken, causes expulsion of the pressurized liquid onto said support member (16b) already impregnated with one or both of the powdered components.

And in the third case (see Figure 9), the curative strip (17) is formed by one of the two said powdered products (the fibrinogen-rich cryoprecipitate extracted from large animals) mixed with a substance. able to give it consistency (eg a collagen) so as to take the form of a blade or sheet (17a) of any suitable shape (rectangular, square, circular, or other) which itself constitutes a support element; said blade (17a) is provided with a usual spray bottle (17b) in which inner chamber is the other powder product (serinoprotease purified from snake venom) already mixed with a diluent liquid.

 Also according to the present invention, the "FIBRINE BIOPOLYMER APPLICATION PROCESS" resulting from the process of obtaining herein provides three sequence of procedures, depending on the application medium to be used.

 [064] In a first sequence of procedures employing, as the applicator means, the now innovated spray bottle (15), the bottle spray nozzle (15c) is pressed at a predetermined distance from the surface of the wound to be treated, whereby the two powder products and the diluent liquid contained in the three independent chambers (15a) of the vial (15) are helically and independently directed outwards through the independent helical channels (15d) and the spray nozzles. also independent (15e), from which the two powder products and the liquid are helically sprayed into the ambient air independently and concomitantly with each other, the three components being then properly mixed in the air during the path between the spray nozzles ( 15e) of the spray nozzle (15c) and the wound to be treated so as to reach the already properly homogenized and polymerized wound by forming a sealed film thereon. transparent and transparent as mentioned above.

More particularly, spraying of the two powder components and the diluent liquid stored in said chambers (15a) is achieved by pumping under high pressure a propellant gas. (preferably inert carbon dioxide) provided within the vial (15) responsible for expelling the said three components from their respective chambers (15a), which, passing through the respective independent ducts (15b), reach the interior of the respective helical channels. (15d) provided on the spray nozzle (15c), reaching the outside through the respective independent spray nozzles (15e).

 In turn, the effective mixing between the two powdered components and the diluent liquid occurs only after spraying them by the spray nozzles (15e) of the spray nozzle (15c) upon reaching the outside of the bottle, which components , inertia, continue to disperse in ambient air in helical motions, intermingling with each other along the path between the nozzle 15c and the surface of the wound to be treated, and forming on said surface the film sealant and transparent above.

 In a second sequence of procedures, which employs, as the applicator means, the adhesive bandage (16) now innovated, the protective strips (16a) of said bandage (16a) are first removed, and the latter is attached. on the user's skin, using the adhesive area provided therein, and disposing the central support member 16b impregnated with one or both of the powdered components just above said wound.

Using the release means (16d) provided in the housing (16c) disposed above the support member (16b), the liquid contained therein is released over said support member (16b). which liquid may or may not be provided with one of the powdered components already diluted therein, then mixing between the three components and also causing the formation of the same sealant and transparent film which is deposited on the injury.

[069] The release of the diluent liquid stored in said The partitioned seal (16c) can be obtained by rupturing the sealing seal which seals a predicted opening between said partitioned (16c) and the support member (16b), which seal, when broken, causes the expulsion of liquid under pressing onto said support member (16b) already impregnated with one or both of powder components.

[070] And in a third sequence of procedures, which creases, as an applicator, the now-innovative bandage (17), the blade (17a) is applied exactly to the wound to be treated, the blade is configured by one of the two components in powder form and a substance which gives it consistency (eg collagen).

 Using the spray bottle (17b) accompanying said blade (17a), it is sprayed onto it at which time the other powder component is already diluted, and then effected. mixing between the three with components, and also causing the formation of the same sealant and transparent film, which is deposited on the wound.

[072] As already mentioned, with the new processes for obtaining and applying fibrin biopolymer, as well as with the new application means of said biopolymer, all the needs were met for the first time and simultaneously. of the present state of the art, enabling the manufacture of a fibrin biopolymer in the form of a low cost, industrially produced final product which no longer requires the freezing of its commercially available components sales (pharmacies and drugstores), and can be purchased and used by the consumer himself, without the need for a prescription, outside the hospital environment and without the need for a medical professional.

[073] This product may be applied to injuries in general, from minor cuts resulting from simple domestic accidents (knife cuts, razor blades, scratches, injuries from tumbling, etc.) to large wounds, which is a highly effective product for stopping bleeding and accelerating tissue healing by stimulating the emergence of new blood vessels.

[074] For all these reasons, the processes and means now developed by the Depositor fulfill the requirements of novelty, inventive activity and industrial application required to obtain a privilege and thus deserve the protection of this Invention Patent.

Claims

 1) "FIBRINE BIOPOLYMER PROCESS", characterized by the following steps:  - Step 1: Dehydration and subsequent crushing of fibrinogen-rich cryoprecipitate extracted from large animals (preferably buffalo - buffalo) to give a first powder component whose properties are kept unchanged for a long period of time, eliminating the need freezing;  - Step 2: Dehydration and subsequent grinding of purified serinoprotease from snake venom, or use of the same component from its synthesis in the laboratory by known methods (produced by recombinant technology for the purpose of extracting its synthetic form, from prokaryotic organisms, eg bacteria, or eukaryotes, eg fungi and yeast, or other methods for the same purpose), so as to result in a second powder component whose properties are kept unchanged for a long time, eliminating the need for freezing;  Step 3: Storing said first powder component obtained in Step 1 in an independent, watertight chamber;  Step 4: storing said second powder component obtained in Step 2 in another independent, watertight chamber;  - Step 5: Storage of a diluent liquid in another independent and watertight chamber; - Step 6: At the time of use, spraying and subsequent mixing between the two powder components and the diluent liquid respectively stored in Steps 3, 4 and 5, resulting in the homogenization and polymerization of the three components, resulting in a sealant film. and transparent, able to stop the bleeding and accelerate healing and tissue recovery;  - - as an alternative to Steps 3, 4 and 6:  Step 7: Mixing said first and second powder components obtained respectively in Steps 1 and 2, and subsequent impregnating them to a support element;  - Step 8: at the time of use, release of the diluent liquid stored in Step 5 on the support element impregnated with the two powdered components obtained in Step 7, resulting in the homogenization and polymerization of the three components, also resulting in the obtaining of a sealant and transparent film capable of stopping bleeding and accelerating tissue healing and recovery by stimulating the emergence of new blood vessels;  - - as another alternative in place of Steps 3, 4 and 6, and Steps 7 and 8:  Step 9: impregnating said first powder component obtained in Step 1 with a support element;  Step 10: Mixing between the second powder component obtained in Step 2 and the diluent liquid stored in Step 5, and consequently storing this mixture in an independent, watertight chamber;  - Step 11: At the time of use, release of the mixture (second powder component + diluent) stored in Step 10 on the support element impregnated with only one of the powder components obtained in Step 9, resulting in the homogenization and polymerization of the three. components, also resulting in a clear, sealing film capable of stopping bleeding and accelerating tissue healing and recovery by stimulating the emergence of new blood vessels; - - and as another alternative to Steps 3, 4 and 6, and Steps 7 to 11: Step 12: Mixing between the first powder component obtained in Step 1 and a substance capable of giving it consistency (eg collagen), resulting in a blade which itself constitutes a support element;  Step 13: Mixing between the second powder component obtained in Step 2 and the diluent liquid stored in Step 5, and consequently storing this mixture in an independent, watertight chamber;  - Step 14: At the time of use, release of the mixture (second powder component + diluent) stored in Step 13 on the support element configured by the first blade-shaped powder component obtained in Step 12, resulting in the homogenization and polymerization. It also results in a clear, sealing film capable of stopping bleeding and accelerating tissue healing and recovery by stimulating the emergence of new blood vessels.  "FIBRINE BIOPOLYMER OBTAINING PROCESS" according to claim 1, characterized in that the dehydration of serinoprotease purified from snake venom, or the use of the same component from its synthesis, and the fibrinogen-rich cryoprecipitate extracted from large animals, be obtained by simple drying, hot air drying, filtration, mechanical pressing, osmotic dehydration, freeze drying (freezing followed by sublimation), or others. 3) "FIBRINE BIOPOLYMER OBTAINING PROCESS" according to claim 1, characterized in that the crushing of serinoprotease purified from snake venom, or the use of the same component from its synthesis, and the fibrinogen-rich cryoprecipitate extracted from large animals, be obtained by grinding, mechanical centrifugation, mechanical bombardment, or others. 4) "FIBRINE BIOPOLYMER PROCESS" Claim 1, characterized in that the diluent liquid contains calcium chloride in its composition.  "FIBRINE BIOPOLYMER PROCESS" according to claim 1, characterized in that it provides for the optional addition of other components, preservatives and stabilizers, to the two powdery products to increase the maintenance of their biological properties.  6) "MEANS OF APPLICATION OF THESE FIBRINE BIOPOLYMER", which provides for three embodiments, whereby, in a first embodiment, said application means are configured by a spray bottle (15) internally provided with three independent and watertight chambers (15a), which house, respectively, the two powder components (serinoprotease purified from snake venom and fibrinogen-rich cryoprecipitate extracted from large animals) and the diluent liquid, and from these chambers ( 15a), separate respective ducts (15b), which, within the spray nozzle (15c) of the vial (15), interconnect with respective equally independent helical channels (15d), duly coiled together, terminating in respective spray nozzles (15e). 7) "APPLICATION OF THE FIBRINE BIOPOLYMER" according to claim 6 and in a second embodiment, characterized in that they are configured by an adhesive bandage (16) provided with an appropriate adhesive area, properly covered by protective strips. (16a), the adhesive area surrounding a central support member (16b), impregnated with one or both of the powdered components (only fibrinogen-rich cryoprecipitate extracted from large animals, or this and serinoprotease purified from venom from above said central support member (16b), there is provided an independent and watertight compartment (16c) within the which diluent liquid is disposed, which may or may not be provided with the other powder component already diluted therein (the serinoprotease purified from snake venom), said compartment (16c) being provided with appropriate release means (16d) which , when triggered, release the outlet of said liquid.  8. "FIBRINE BIOPOLYMER APPLICATION MEANS" according to claim 7, characterized in that said diluent liquid release means (16d) stored in said compartment (16c) are configured by an opening seal seal. between said housing (16c) and the support member (16b), which seal is responsible for expelling the pressurized liquid onto said support member (16b), impregnated with one or both of the powdered components.  9) "APPLICATION OF THE FIBRINE BIOPOLYMER" according to claim 6 and in a third embodiment, characterized in that they are configured by a curing strip (17) configured by one of the two said powder products ( fibrinogen-rich cryoprecipitate extracted from large animals) mixed with a substance capable of giving it consistency, such as collagen, taking the form of a lamina or leaf (17a), which forms a supporting element, said lamina (17a ) is supplied with a usual spray bottle (17b), in which inner chamber is the other powdered product (serinoprotease purified from snake venom) already mixed with a diluent liquid. 10) "FIBRINE BIOPOLYMER APPLICATION PROCESS", which provides for three sequences of procedures, depending on the applicator medium used, and when the spray bottle (15) is used, this application process is characterized by the nozzle pressing. bottle sprayer (15c) at a predetermined distance from the surface of the wound to be treated, whereby the two powder products (serinoprotease purified from snake venom and fibrinogen-rich cryoprecipitate extracted from large animals) and the diluent liquid contained in the three independent chambers (15a) of the vial (15 ) are helically directed outwards through the independent helical channels (15d) and also independent spray nozzles (15e), from which both powder and liquid are helically sprayed into the ambient air independently and concomitantly. the three components then properly mixed in the air, during the course between the spray nozzles (15e) of the spray nozzle (15c) and the wound to be treated, reaching said already homogenized and polymerized wound and forming a sealant film thereon. and transparent.  11. "FIBRINE BIOPOLYMER APPLICATION PROCESS" according to claim 10, characterized in that the spraying of the two powder components and the diluent liquid stored in said chambers (15a) is obtained by pumping under high pressure a propellant gas, preferably inert carbon dioxide, provided within the vial (15), responsible for expelling the three said components from their respective chambers (15a), which, passing through the respective independent ducts (15b), reach the interior of the respective independent helical channels (15d) provided in the spray nozzle (15c), reaching outwards through respective equally independent spray nozzles (15e). 12. "FIBRINE BIOPOLYMER APPLICATION PROCESS" according to Claim 10, characterized in that mixing between the two powder components and the diluent liquid occurs after their spraying by the spray nozzles (15e) of said spray nozzle. (15c), upon reaching the outside of the bottle, these components which, inertia, continue to disperse in ambient air in helical motions, mixing with each other along the path between the spray nozzles (15e) of the spray nozzle (15c) and the surface of the wound to be treated, and forming on said surface said transparent sealant film.  13. "FIBRINE BIOPOLYMER APPLICATION PROCESS" according to claim 10 and when using the adhesive bandage (16), characterized by the removal of the protective strips (16a) from said bandage (16), by fixing it the latter on the user's skin using the adhesive area provided for therein and the arrangement of the central support member 16b impregnated with one or both of the powdered components (only the fibrinogen-rich cryoprecipitate extracted from large animals or and serinoprotease purified from snake venom), just above said wound, and by releasing the release means (16d) provided in the housing (16c) disposed above the support member (16b), the outlet of the liquid contained therein over said support member (16b), which liquid may or may not be provided with one of the powder components already diluted therein (serinoprotease purified from venom poison). snake), mixing the three components and forming, on the surface of the wound, said sealing and transparent film. 14. "FIBRINE BIOPOLYMER APPLICATION PROCESS" according to claim 13, characterized in that the release of the diluent liquid stored in said compartment (16c) is obtained by breaking a sealing seal from a predicted opening between the said housing (16c) and support member (16b), which seal is responsible for expelling the pressurized liquid onto said support member (16b) impregnated with one or both of the powdered components. 15. "FIBRINE BIOPOLYMER APPLICATION PROCESS" according to claim 10, and when using the dressing strip (17) characterized by applying the blade (17a) exactly over the wound to be treated, the blade is configured. one of the two powdered components (fibrinogen-rich cryoprecipitate extracted from large animals) and a substance which gives it consistency, such as collagen, using the spray bottle (17b) accompanying said slide ( 17a), the mixture in which the other powder component is already diluted (serinoprotease purified from snake venom) is sprayed on it, mixing between the three components and forming on the surface of the wound , said transparent sealing film.