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WO2018191801A1 - Procédé d'obtention d'un biopolymère de fibrine, moyens d'application dudit biopolymère de fibrine et procédé d'application dudit biopolymère de fibrine - Google Patents

Procédé d'obtention d'un biopolymère de fibrine, moyens d'application dudit biopolymère de fibrine et procédé d'application dudit biopolymère de fibrine Download PDF

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Publication number
WO2018191801A1
WO2018191801A1 PCT/BR2018/050102 BR2018050102W WO2018191801A1 WO 2018191801 A1 WO2018191801 A1 WO 2018191801A1 BR 2018050102 W BR2018050102 W BR 2018050102W WO 2018191801 A1 WO2018191801 A1 WO 2018191801A1
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WIPO (PCT)
Prior art keywords
components
biopolymer
powder
fibrine
independent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/BR2018/050102
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English (en)
Portuguese (pt)
Inventor
Moacyr RAMOS BIGHETT
Ana Silvia SARTORI BARRAVIERA SEABRA FERREIRA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kaivo Pesquisa E Desenvolvimento Em Saude Ltda
Original Assignee
Kaivo Pesquisa E Desenvolvimento Em Saude Ltda
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Publication of WO2018191801A1 publication Critical patent/WO2018191801A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A61L24/106—Fibrin; Fibrinogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive bandages or dressings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/16—Blood plasma; Blood serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/58—Reptiles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B7/00—Spraying apparatus for discharge of liquids or other fluent materials from two or more sources, e.g. of liquid and air, of powder and gas
    • B05B7/02—Spray pistols; Apparatus for discharge
    • B05B7/08—Spray pistols; Apparatus for discharge with separate outlet orifices, e.g. to form parallel jets, i.e. the axis of the jets being parallel, to form intersecting jets, i.e. the axis of the jets converging but not necessarily intersecting at a point
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/00491—Surgical glue applicators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/00491—Surgical glue applicators
    • A61B2017/00495—Surgical glue applicators for two-component glue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0413—Blood
    • A61M2202/0445—Proteins
    • A61M2202/0447—Glycoproteins
    • A61M2202/045—Fibrin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745—Blood coagulation or fibrinolysis factors
    • C07K14/75—Fibrinogen

Definitions

  • PROCESS FOR OBTAINING FIBRINE BIOPOLYMER MEANS OF APPLYING SUCH FIBRINE BIOPOLYMER, AND PROCESS OF APPLYING FIBRINE BIOPOLYMER.
  • 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.
  • 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).
  • 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”.
  • 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.
  • fibrin biopolymers 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.
  • fibrin biopolymer is that described in BR PI 9103724-7, published 30/03/1993, concerning a "COBRA POIS DERIVATED FIBRIN ADHESIVE FOR PREPARATION".
  • 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.
  • 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.
  • 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.
  • these devices can only be handled by medical professionals (doctors or nurses) who are already used to operating surgical instruments.
  • fluidization is the process by which solid particles are transformed into liquid state by suspending them in a gas or liquid.
  • a carrier gas preferably carbon dioxide or nitrogen
  • a solution preferably water
  • 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.
  • 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.
  • 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.
  • 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.
  • OTC over the counter
  • 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.
  • fibrin biopolymer 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".
  • 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.
  • a serinoprotease purified from snake venom a fibrinogen-rich cryoprecipitate extracted from large animals, preferably buffalo (buffalo)
  • a diluent. configured by calcium chloride.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • two powdery products are obtained, the properties of which are kept unchanged for a long time, thus eliminating the need for freezing.
  • other components such as preservatives and stabilizers may be added to further enhance and ensure the maintenance of their biological properties.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the powdered blade product when using the biopolymer to treat any wound, 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.
  • Such application means may be configured by a spray bottle, an adhesive bandage or a curative strip.
  • 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.
  • 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;
  • 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;
  • 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);
  • a substance that gives it consistency eg collagen
  • the purified serinoprotease purified from from snake venom the purified serinoprotease purified from from snake venom
  • 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.
  • the 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.
  • the 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.
  • a substance capable of giving it consistency eg collagen
  • 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.
  • 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.
  • 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;
  • FIGS. 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;
  • 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.
  • This invention relates to a "FIBRINE BIOPOLYMER PROCESS", "MEANS OF APPLICATION OF THE FIBRIN BIOPOLYMER”, and the "FIBRINE BIOPOLYMER APPLICATION PROCESS”.
  • 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).
  • 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;
  • 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;
  • Steps 3, 4 and 6, and Steps 7 and 8 are 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;
  • 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;
  • a substance capable of giving it consistency eg collagen
  • 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.
  • 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.
  • the diluent liquid contains in its composition calcium chloride.
  • 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).
  • 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).
  • the adhesive bandage (16) of any suitable shape 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.
  • 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.
  • 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.
  • a substance eg a collagen
  • 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.
  • 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.
  • 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).
  • a propellant gas preferably inert carbon dioxide
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.

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Abstract

L'invention concerne un procédé d'obtention d'un biopolymère de fibrine, des moyens d'application dudit biopolymère de fibrine et un procédé d'application dudit biopolymère de fibrine, permettant la déshydratation et le broyage des constituants du biopolymère (la sérinoprotéase purifiée à partir de venin de serpent et le cryoprécipité riche en fibrinogène extrait d'animaux de grande taille), ce qui donne lieu à l'obtention de deux constituants pulvérulents, dont les propriétés sont maintenues intactes pendant une période prolongée, aucune congélation n'étant nécessaire. Ces deux constituants en poudre sont fournis séparément ou sont mélangés entre eux et imprégnés dans un élément de support, ou seul l'un deux est imprégné dans un élément de support, ou encore seul l'un deux est mélangé à une substance lui donnant une consistance. Des moyens applicateurs appropriés sont prévus, ces moyens impliquant la fourniture d'un liquide diluant stocké séparément ou mélangé à l'un des constituants en poudre.
PCT/BR2018/050102 2017-04-18 2018-04-16 Procédé d'obtention d'un biopolymère de fibrine, moyens d'application dudit biopolymère de fibrine et procédé d'application dudit biopolymère de fibrine Ceased WO2018191801A1 (fr)

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BRBR102017008027-7 2017-04-18
BR102017008027-7A BR102017008027B1 (pt) 2017-04-18 2017-04-18 Processo de obtenção de biopolímero de fibrina, meios de aplicação do referido biopolímero de fibrina, e processo de aplicação do referido biopolímero de fibrina

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WO2018191801A1 true WO2018191801A1 (fr) 2018-10-25

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4427651A (en) * 1981-06-25 1984-01-24 Serapharm Michael Stroetmann Enriched plasma derivative for enhancement of wound closure and coverage
US6454786B1 (en) * 1996-11-15 2002-09-24 Bristol-Myers Squibb Company Devices and methods for applying a mixture of two or more liquid components to form a biomaterial
US7189410B1 (en) * 1990-11-27 2007-03-13 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
EP1706132B1 (fr) * 2003-12-23 2011-03-23 Sewon Cellontech Co., Ltd. Composition pour la therapeutique du cartilage et son procede d'utilisation
US20160015792A1 (en) * 2013-03-07 2016-01-21 Profibrix Bv Powder formulation comprising thrombin and fibrinogen
BR102014011436A2 (pt) * 2014-05-12 2016-02-23 Univ Estadual Paulista Julio D selante de fibrina para uso tópico, método de formação do mesmo e seu uso
US20160058908A1 (en) * 2014-09-03 2016-03-03 Osaka University Method for producing laminate of sheet-shaped cell culture and fibrin gel

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4427651A (en) * 1981-06-25 1984-01-24 Serapharm Michael Stroetmann Enriched plasma derivative for enhancement of wound closure and coverage
US7189410B1 (en) * 1990-11-27 2007-03-13 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
US6454786B1 (en) * 1996-11-15 2002-09-24 Bristol-Myers Squibb Company Devices and methods for applying a mixture of two or more liquid components to form a biomaterial
EP1706132B1 (fr) * 2003-12-23 2011-03-23 Sewon Cellontech Co., Ltd. Composition pour la therapeutique du cartilage et son procede d'utilisation
US20160015792A1 (en) * 2013-03-07 2016-01-21 Profibrix Bv Powder formulation comprising thrombin and fibrinogen
BR102014011436A2 (pt) * 2014-05-12 2016-02-23 Univ Estadual Paulista Julio D selante de fibrina para uso tópico, método de formação do mesmo e seu uso
US20160058908A1 (en) * 2014-09-03 2016-03-03 Osaka University Method for producing laminate of sheet-shaped cell culture and fibrin gel

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
THOMAZINI-SANTOS, I. A. ET AL.: "Surgical adhesives", J. VENOM. ANIM. TOXINS, vol. 7, no. 2, 2001, Retrieved from the Internet <URL:http://dx.doi.org/10.1590/S0104-79302001000200002> *

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BR102017008027A2 (pt) 2018-10-30

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