WO2021092670A1 - Improvements made to fixed-rotor centrifuges for producing autologous platelet-rich fibrin matrix for non-transfusion therapeutic purposes - Google Patents
Improvements made to fixed-rotor centrifuges for producing autologous platelet-rich fibrin matrix for non-transfusion therapeutic purposes Download PDFInfo
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- WO2021092670A1 WO2021092670A1 PCT/BR2020/050471 BR2020050471W WO2021092670A1 WO 2021092670 A1 WO2021092670 A1 WO 2021092670A1 BR 2020050471 W BR2020050471 W BR 2020050471W WO 2021092670 A1 WO2021092670 A1 WO 2021092670A1
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- 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
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- B04B1/00—Centrifuges with rotary bowls provided with solid jackets for separating predominantly liquid mixtures with or without solid particles
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- the present invention patent deals with improvements in fixed-rotor centrifuge for the production of autologous leukoplakelet fibrin matrix for non-transfusion therapeutic purposes and applicability in regenerative medicine where, notably, the so-called innovative fixed-rotor centrifuge provides for a specific idealized angle to give a functional identity to the equipment, serving to make maximum use of the cellular content of the blood fraction by centrifugation.
- leukoplakelet fibrin matrices have and that qualify them as an autologous therapeutic agent for surgical purposes are: (i) topical hemostasis in bleeding beds; (ii) accelerating the migration of fibroblasts required in tissue repair and wound closure; (iii) binder of biomaterials for bone grafting; (iv) membranes to cover exposed surgical areas; (v) surgical biological adhesive.
- Said bench centrifuges are idealized for laboratory routine and have reduced dimensions that contribute to the operational logistics of medical and dental offices, however, they do not have a sanitary classification as 'Medicai Device', that is, they do not include devices intended to be used for medical purposes.
- the flow-dividing mechanism includes an adjustable flow-divider valve and a flow-guide channel, and the adjustable flow-divider valve is configured to adjust the relative positions of the flow-guide channel and the discharge orifice, thus implementing the division of blood flow components in the bottom layer of the centrifuge tube.
- the centrifugal device can be used to manufacture platelet-rich plasma in a simple and convenient way, and can improve the efficiency of clinical operation.
- n ⁇ . BR11.2015.010040-6 refers to a continuous flow centrifuge bowl that includes a rotating outer body and a top and bottom core that are rotatable with the outer body.
- the bottom core has a wall that extends proximally from a bottom wall.
- the proximally extending end is radially outwardly from at least a portion of the top nucleus and, together with the top nucleus, defines a primary separation region, in which an initial separation of whole blood occurs.
- the vat may also have a secondary separation region located between the top core and the outer body, and a rotating seal that couples an inlet and two outlet windows to the outer body.
- the inlet window can be connected to an inlet tube that extends distally to the region of introduction of whole blood. Additionally, one of the exit windows can be connected to an extraction tube that extends to a region below the bottom core.
- US2005059540 refers to a centrifuge apparatus for processing blood comprising a lower spring support plate; an upper support plate; an axial inlet / outlet for blood to be processed and blood components processed, the axial inlet / outlet being fixed to the upper support plate by a rotating seal assembly; a variable volume separation chamber mounted between the lower support plate and the upper support plate, the variable volume separation chamber being fluidly connected to the axial inlet / outlet; a pump fluidly connected to the axial inlet / outlet; and a rotary drive unit connected to the bottom support plate.
- the upper support plate is fixed vertically and the lower spring support plate is mounted on springs that maintain pressure in the variable volume separation chamber and allow the lower support plate to move vertically.
- Another objective of this invention is to present a fixed rotor centrifuge for the production of leukoplakelet fibrin matrix, where the rotor pushes the leukocyte and platelet content to the upper portion, promoting greater use of the cellular content.
- Another objective is to present a fixed rotor centrifuge for the production of leukoplakelet fibrin matrix that generates an operational identity that stands out for the biological advantage of the product obtained.
- the objective of this invention is to present a fixed-rotor centrifuge for the production of leukoplakelet fibrin matrix that ensures better use of the cellular and plasma content of human blood for optimized tissue repair.
- the main observable effect of the innovative fixed rotor centrifuge is to obtain larger areas in the fibrin matrix, that is, the leukoplakt pellet area and the total area of the matrix.
- the advantage of this feature is the use of blood to obtain matrices with greater power to cover the wounds, that is, clinically, considering the principle of rationality in the therapeutic use of human blood is a significant advantage.
- figure 1 represents a longitudinal section view A.
- a of the fixed rotor with an angle of 25 ° in relation to the central axis of the motor;
- figure 2 shows a flowchart describing the steps for obtaining the autologous leukoplakelet fibrin matrix
- figure 3 reveals cytogram images by centrifugation in rotors, the ⁇ 'representation with 25 ° rotor and' B 'representation with 45 ° rotor;
- figure 4 shows cell concentration tables for morphological investigation
- figure 5 represents a graph of the macroscopy of the membranes
- Figure 6 reveals photographic images of micrographs of the body fragment of the LPRF matrix obtained in 80-2B at 400xg / 10 min in increments of 33x, HOx, 10,000x, 3,700x, 5,000x and 10,000x. Condensed fibrin fibers and fibrils, small platelet agglomerations and exposure of superficial exosomal content;
- Figure 7 represents photographic images of the fibrin matrix micrograph of a cross-section of the body obtained in FF25 at 200xg / 10min with a 20x magnification.
- ⁇ 'bottom of the metallic support ⁇ 'B' peripheral region of the fibrin matrix; 'C central region of the matrix;
- Micrograph with an increase of 100x of the cross section 'C showing areas Cl - fibrils with cell impregnation - and C2 - dense fibrin borders delimiting chambers or spaces; (3) Enlargement of the Cl zone with evident cell and platelet agglomeration in the center of the matrix; 'D' 4, 5 and 6.
- Figure 8 reveals images of dimensional differences in the macroscopic evaluation of LPRF matrices obtained at different angles.
- the scale was standardized in mm 2 .
- the total area of specimens obtained at an angle of 25 ° was 13.6% greater than those observed at 33 ° and 45 °.
- the pelletizing zone was approximately 37% larger.
- the present invention patent refers to "IMPROVEMENTS IN FIXED ROTOR CENTRIFUGAL FOR PRODUCTION OF AUTOLOGICAL LEUKPLAQUETARY FIBRINE MATRIX FOR NON-TRANSFUSIONAL THERAPEUTIC PURPOSES", more precisely it is a rotor centrifuge. (10) for the production of an autologous leukoplakelet fibrin matrix for non-transfusion therapeutic purposes and applicability in regenerative medicine.
- said centrifuge (10) provides a rotor (11) attached to the magnetic induction motor (Mt) with multiple cassettes (12) positioning devices tubes (Tb) for the storage of blood samples collected in a vacuum (not shown), arranged at an angle (a), preferably at 25 °, it generates in the blood a restraint to the indiscriminate cell scattering and guides its selective stratification according to the relative density of the elements blood.
- Mt magnetic induction motor
- Tb positioning devices tubes
- a cycle (CL) formed by low speed centrifugation with torque reduction is foreseen, preferentially indicating low speed with increasing acceleration from 20 to 1570 rpm for 30 seconds, followed by a stabilization in the chosen range of 1570, which corresponds to the relative centrifugal force of 200 xg for 10 minutes, followed by a deceleration without braking at the end of the cycle (CL).
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Abstract
The present invention relates to a fixed-rotor centrifuge (10) for producing an autologous platelet-rich fibrin matrix for non-transfusion therapeutic purposes and use in regenerative medicine. Said centrifuge (10) has a rotor (11) attached to the magnetic induction motor (Mt) having multiple positioning cassettes (12) for vacuum blood sample collection tubes (Tb) that are arranged at an angle (α) of 25° to restrict indiscriminate cell dispersal in the blood and orienting the selective stratification thereof according to the relative density of the blood elements. A cycle (CL) is associated with the angle (α) of each collection tube (Tb), comprising low-rotation centrifuging with torque reduction, followed by increasing acceleration and stabilization in the chosen centrifugal force range. Deceleration without braking is also provided at the end of the cycle (CL).
Description
APERFEIÇOAMENTOS EM CENTRÍFUGA DE ROTOR FIXO PARA PRODUÇÃO DE MATRIZ DE FIBRINA LEUCOPLAQUETÁRIA AUTÓLOGA PARA FINS TERAPÊUTICOS IMPROVEMENTS IN A FIXED ROTOR CENTRIFUGAL FOR THE PRODUCTION OF AUTOLOGOUS LEUCOPLAQUETARY MATRIX FOR THERAPEUTIC PURPOSES
NÃO-TRANSFUSIONAIS NON-TRANSFUSIONAL
CAMPO TÉCNICO DA INVENÇÃO TECHNICAL FIELD OF THE INVENTION
[001] A presente patente de invenção trata de aperfeiçoamentos em centrífuga de rotor fixo para produção de matriz de fibrina leucoplaquetária autóloga para fins terapêuticos não-transfusionais e aplicabilidade em medicina regenerativa onde, notadamente, dita inovada centrífuga de rotor fixo prevê um ângulo específico idealizado para conferir uma identidade funcional ao equipamento, servindo para aproveitamento máximo do conteúdo celular da fração sanguínea por centrifugação. HISTÓRICO DA INVENÇÃO [001] The present invention patent deals with improvements in fixed-rotor centrifuge for the production of autologous leukoplakelet fibrin matrix for non-transfusion therapeutic purposes and applicability in regenerative medicine where, notably, the so-called innovative fixed-rotor centrifuge provides for a specific idealized angle to give a functional identity to the equipment, serving to make maximum use of the cellular content of the blood fraction by centrifugation. BACKGROUND OF THE INVENTION
[002] As principais propriedades biológicas que as matrizes de fibrina leucoplaquetária possuem e que as qualificam como agente terapêutico autólogo com finalidades cirúrgicas são: (i) hemostasia tópica em leitos sangrantes; (ii) acelerador da migração de fibroblastos demandados no reparo tecidual e fechamento de feridas; (iii) aglutinante de biomateriais para enxertia óssea; (iv) membranas para cobertura de áreas cirúrgicas expostas; (v) adesivo biológico cirúrgico. [002] The main biological properties that leukoplakelet fibrin matrices have and that qualify them as an autologous therapeutic agent for surgical purposes are: (i) topical hemostasis in bleeding beds; (ii) accelerating the migration of fibroblasts required in tissue repair and wound closure; (iii) binder of biomaterials for bone grafting; (iv) membranes to cover exposed surgical areas; (v) surgical biological adhesive.
[003] Atualmente, existe no mercado equipamentos que se aplicam à técnica de obtenção de produtos sanguíneos autólogos para fins terapêuticos. Entretanto, partiram de adaptações de centrífugas de laboratório com finalidades diagnósticas comuns nas áreas acadêmicas e laboratoriais. [003] Currently, there is equipment on the market that applies to the technique of obtaining autologous blood products for therapeutic purposes. However, they started with adaptations of laboratory centrifuges with common diagnostic purposes in the academic and laboratory areas.
[004] Ditas centrífugas de bancada são idealizadas para rotina laboratorial e apresentam dimensões reduzidas que contribuem para a logística operacional dos consultórios médico-odontológicos, porém, não possuem classificação sanitária como 'Medicai Device', ou seja, não compreendem dispositivos destinados a serem utilizados para fins médicos. [004] Said bench centrifuges are idealized for laboratory routine and have reduced dimensions that contribute to the operational logistics of medical and dental offices, however, they do not have a sanitary classification as 'Medicai Device', that is, they do not include devices intended to be used for medical purposes.
[005] Em recentes evoluções sobre os concentrados sanguíneos foram incorporadas na prática clínica do cirurgião-dentista e de outros profissionais da área médica. [005] In recent developments on blood concentrates, they have been incorporated into the clinical practice of dentists and other medical professionals.
[006] Ocorre que, ditas centrífugas de laboratório não foram desenvolvidas com a intenção de fracionar seletivamente o sangue, mas de simplesmente tornar eficiente e
eficaz a sedimentação de todos os elementos figurados, ou seja, eritrócitos, leucócitos e plaquetas. [006] It so happens that, said laboratory centrifuges were not developed with the intention of selectively fractionating the blood, but simply to make efficient and sedimentation of all figured elements is effective, that is, erythrocytes, leukocytes and platelets.
[007] Outro inconveniente reside no fato dos equipamentos supracitados apresentarem custo significativo e não possuírem parâmetros cambiáveis para otimizar a centrifugação para fins terapêuticos. [007] Another drawback lies in the fact that the aforementioned equipment has a significant cost and does not have changeable parameters to optimize centrifugation for therapeutic purposes.
ANÁLISE DO ESTADO DA TÉCNICA ANALYSIS OF THE STATE OF THE TECHNIQUE
[008] Em pesquisa realizada em bancos de dados especializados foram encontrados documentos referentes à centrífugas para produção de matriz de fibrina leucoplaquetária autóloga para fins terapêuticos não-transfusionais, tal como, o documento de n^. US2016325277 que trata de aparelho de centrifugação para separar os componentes do sangue inclui um tubo de centrifugação e um mecanismo de divisão de fluxo, e o mecanismo de divisão de fluxo é fixado no fundo do tubo de centrífuga. Além disso, o fundo do tubo de centrifugação é ainda dotado de um orifício de descarga. O mecanismo de divisão de fluxo inclui uma válvula divisora de fluxo ajustável e um canal guia de fluxo, e a válvula divisora de fluxo ajustável é configurada para ajustar as posições relativas do canal guia de fluxo e do orifício de descarga, implementando assim a divisão de fluxo do sangue componentes na camada inferior do tubo de centrifugação. O aparelho centrífugo pode ser usado para fabricar plasma rico em plaquetas de uma maneira simples e conveniente, e pode melhorar a eficiência da operação clínica. [008] In research carried out in specialized databases, documents were found referring to centrifuges for the production of autologous leukoplakelet fibrin matrix for non-transfusion therapeutic purposes, such as the document of n ^. US2016325277 which deals with centrifugation apparatus for separating blood components includes a centrifuge tube and a flow dividing mechanism, and the flow dividing mechanism is fixed to the bottom of the centrifuge tube. In addition, the bottom of the centrifuge tube is also provided with a discharge orifice. The flow-dividing mechanism includes an adjustable flow-divider valve and a flow-guide channel, and the adjustable flow-divider valve is configured to adjust the relative positions of the flow-guide channel and the discharge orifice, thus implementing the division of blood flow components in the bottom layer of the centrifuge tube. The centrifugal device can be used to manufacture platelet-rich plasma in a simple and convenient way, and can improve the efficiency of clinical operation.
[009] O documento de n^. BR11.2015.010040-6 se refere a uma cuba de centrífuga de fluxo contínuo que inclui um corpo externo rotativo e um núcleo de topo e um de fundo que são rotativos com o corpo externo. O núcleo de fundo tem uma parede que se estende de forma proximal a partir de uma parede de fundo. A extremidade que se estende de forma proximal é radialmente para fora a partir de pelo menos uma porção do núcleo de topo e, em conjunto com o núcleo de topo, define uma região de separação primária, na qual uma separação inicial do sangue total ocorre. A cuba também pode ter uma região de separação secundária localizada entre o núcleo de topo e o corpo externo, e um selo rotativo que acopla uma janela de entrada e duas janelas de saída ao corpo externo. A janela de entrada pode ser conectada a um tubo de entrada que se estende de forma distai para a região de introdução de sangue total. Adicionalmente,
uma das janelas de saída pode ser conectada a um tubo de extração que se estende para uma região abaixo do núcleo de fundo. [009] The document of n ^. BR11.2015.010040-6 refers to a continuous flow centrifuge bowl that includes a rotating outer body and a top and bottom core that are rotatable with the outer body. The bottom core has a wall that extends proximally from a bottom wall. The proximally extending end is radially outwardly from at least a portion of the top nucleus and, together with the top nucleus, defines a primary separation region, in which an initial separation of whole blood occurs. The vat may also have a secondary separation region located between the top core and the outer body, and a rotating seal that couples an inlet and two outlet windows to the outer body. The inlet window can be connected to an inlet tube that extends distally to the region of introduction of whole blood. Additionally, one of the exit windows can be connected to an extraction tube that extends to a region below the bottom core.
[010] O documento de n^. US2005059540 refere-se a aparelho de centrifugação para processar sangue compreendendo uma placa de suporte de mola inferior; uma placa de suporte superior; uma entrada / saída axial para o sangue ser processado e processado componentes do sangue, a entrada / saída axial sendo fixada à placa de suporte superior por um conjunto de vedação rotativo; uma câmara de separação de volume variável montada entre a placa de suporte inferior e a placa de suporte superior, estando a câmara de separação de volume variável ligada de modo fluido entrada/saída axial; uma bomba conectada de forma fluida à entrada/saída axial; e uma unidade de acionamento rotativa conectada à placa de suporte inferior. A placa de suporte superior é fixada verticalmente e a placa de suporte inferior por mola é montada em molas que mantêm a pressão na câmara de separação de volume variável e permitem que a placa de suporte inferior se mova verticalmente. [010] The document of n ^. US2005059540 refers to a centrifuge apparatus for processing blood comprising a lower spring support plate; an upper support plate; an axial inlet / outlet for blood to be processed and blood components processed, the axial inlet / outlet being fixed to the upper support plate by a rotating seal assembly; a variable volume separation chamber mounted between the lower support plate and the upper support plate, the variable volume separation chamber being fluidly connected to the axial inlet / outlet; a pump fluidly connected to the axial inlet / outlet; and a rotary drive unit connected to the bottom support plate. The upper support plate is fixed vertically and the lower spring support plate is mounted on springs that maintain pressure in the variable volume separation chamber and allow the lower support plate to move vertically.
[011] Os documentos supracitados, apesar de pertencerem ao mesmo campo de aplicação diferenciam-se do presente invento em questão, como se verá adiante, garantindo, assim, que o mesmo atenda, plenamente, aos requisitos legais de patenteabilidade. [011] The aforementioned documents, despite belonging to the same field of application, differ from the present invention in question, as will be seen below, thus ensuring that it fully meets the legal requirements for patentability.
OBJETIVOS DA INVENÇÃO OBJECTIVES OF THE INVENTION
[012] É, portanto, objetivo da presente invenção, apresentar uma centrífuga de rotor fixo para produção de matriz de fibrina leucoplaquetária autóloga para fins terapêuticos não-transfusionais para aplicabilidade em medicina regenerativa cuja nova angulação do rotor proporciona a utilização da força centrífuga relativa - FCR - não apenas para prover a sedimentação, mas também de promover, em função das densidades diferenciais dos elementos figurados do sangue, o maior aproveitamento do conteúdo plasmático e leucoplaquetário. [012] It is, therefore, objective of the present invention, to present a fixed rotor centrifuge for the production of autologous leukoplakelet fibrin matrix for non-transfusion therapeutic purposes for applicability in regenerative medicine whose new rotor angulation provides the use of relative centrifugal force - FCR - not only to provide sedimentation, but also to promote, due to the differential densities of the figured elements of the blood, the greater use of the plasma and leukoplakelet content.
[013] Outro objetivo desta invenção é apresentar uma centrífuga de rotor fixo para produção de matriz de fibrina leucoplaquetária, onde o rotor empurra para a porção superior o conteúdo de leucócitos e plaquetas, promovendo maior aproveitamento do conteúdo celular.
[014] É, ainda, objetivo desta invenção apresentar centrífuga de rotor fixo para produção de matriz de fibrina leucoplaquetária cujas dimensões reduzidas exige menor potencial elétrico. Isto promove menor energia cinética no conjunto, bem como menores níveis de variações térmicas sofridas durante o funcionamento. [013] Another objective of this invention is to present a fixed rotor centrifuge for the production of leukoplakelet fibrin matrix, where the rotor pushes the leukocyte and platelet content to the upper portion, promoting greater use of the cellular content. [014] It is also the objective of this invention to present a fixed rotor centrifuge for the production of leukoplakelet fibrin matrix whose reduced dimensions require less electrical potential. This promotes less kinetic energy in the assembly, as well as lower levels of thermal variations suffered during operation.
[015] Outro objetivo é apresentar uma centrífuga de rotor fixo para produção de matriz de fibrina leucoplaquetária que gera uma identidade operacional que prime pela vantagem biológica do produto obtido. [015] Another objective is to present a fixed rotor centrifuge for the production of leukoplakelet fibrin matrix that generates an operational identity that stands out for the biological advantage of the product obtained.
[016] É, ainda, objetivo desta invenção apresentar uma centrífuga de rotor fixo para produção de matriz de fibrina leucoplaquetária que apresenta adequação sanitária às legislações internacionais. [016] It is also the objective of this invention to present a fixed rotor centrifuge for the production of leukoplakelet fibrin matrix that presents sanitary adequacy to international legislation.
[017] É objetivo desta invenção apresentar uma centrífuga de rotor fixo para produção de matriz de fibrina leucoplaquetária que garante melhor aproveitamento do conteúdo celular e plasmático do sangue humano para o reparo tecidual otimizado. [017] The objective of this invention is to present a fixed-rotor centrifuge for the production of leukoplakelet fibrin matrix that ensures better use of the cellular and plasma content of human blood for optimized tissue repair.
[018] O principal efeito observável da inovada centrífuga de rotor fixo consiste na obtenção de maiores áreas na matriz de fibrina, ou seja, área de peletização leucoplaqutária e área total da matriz. A vantagem desta característica está no aproveitamento do sangue para obtenção de matrizes com maior poder de cobertura das feridas, isto clinicamente, considerando o princípio da racionalidade do uso terapêutico do sangue humano é uma vantagem significativa. [018] The main observable effect of the innovative fixed rotor centrifuge is to obtain larger areas in the fibrin matrix, that is, the leukoplakt pellet area and the total area of the matrix. The advantage of this feature is the use of blood to obtain matrices with greater power to cover the wounds, that is, clinically, considering the principle of rationality in the therapeutic use of human blood is a significant advantage.
DESCRIÇÃO DAS FIGURAS DESCRIPTION OF THE FIGURES
[019] A complementar a presente descrição de modo a obter uma melhor compreensão das características do presente invento e de acordo com uma preferencial realização prática do mesmo, acompanha a descrição, em anexo, um conjunto de desenhos, onde, de maneira exemplificada, embora não limitativa, se representou seu funcionamento: [019] To complement the present description in order to obtain a better understanding of the characteristics of the present invention and according to a preferred practical realization thereof, the description, attached, is a set of drawings, where, in an exemplified manner, although non-limiting, its functioning was represented:
[020] a figura 1 representa uma vista em corte longitudinal A. A do rotor fixo com angulação de 25° em relação ao eixo central do motor; [020] figure 1 represents a longitudinal section view A. A of the fixed rotor with an angle of 25 ° in relation to the central axis of the motor;
[021] a figura 2 mostra um fluxograma descrevendo os passos para a obtenção da matriz de fibrina Leucoplaquetária autóloga; [021] figure 2 shows a flowchart describing the steps for obtaining the autologous leukoplakelet fibrin matrix;
[022] a figura 3 revela imagens de citogramas por centrifugação em rotores, sendo a
representação Ά' com rotor de 25°e representação 'B' com rotor de 45°; [022] figure 3 reveals cytogram images by centrifugation in rotors, the Ά 'representation with 25 ° rotor and' B 'representation with 45 ° rotor;
[023] a figura 4 mostra tabelas de concentração celular para investigação morfológica; [024] a figura 5 representa um gráfico da macroscopia das membranas; [023] figure 4 shows cell concentration tables for morphological investigation; [024] figure 5 represents a graph of the macroscopy of the membranes;
[025] a figura 6 revela imagens fotográficas de micrografias de fragmento do corpo da matriz de LPRF obtida em 80-2B a 400xg /10 min com aumentos de 33x, HOx, l.OOOx, 3.700x, 5.000x e lO.OOOx. Fibras e fibrilas de fibrina condensadas, pequenas aglomerações plaquetárias e exposição de conteúdo exossômico superficial; [025] Figure 6 reveals photographic images of micrographs of the body fragment of the LPRF matrix obtained in 80-2B at 400xg / 10 min in increments of 33x, HOx, 10,000x, 3,700x, 5,000x and 10,000x. Condensed fibrin fibers and fibrils, small platelet agglomerations and exposure of superficial exosomal content;
[026] a figura 7 representa imagens fotográficas da micrografia da matriz de fibrina de um corte transversal do corpo obtida em FF25 a 200xg/10min com aumento de 20x. onde (1) Ά' fundo do suporte metálico; 'B' região periférica da matriz de fibrina; 'C região central da matriz; (2) Micrografia com aumento de lOOx do corte transversal 'C exibindo áreas Cl - fibrilas com impregnação celular - e C2 - bordas de fibrina densas delimitando câmaras ou espaços; (3) Ampliação da zona Cl com evidente aglomeração celular e plaquetária no centro da matriz; 'D' 4, 5 e 6. Ampliações de l.OOOx, 2.500x e lO.OOOx demonstrando a presença de leucócitos e plaquetas íntegros no interior da rede tridimensional de fibrina e fibras e fibrilas com rugosidade superficial marcada por impregnação de exossomos e peptídeos; [026] Figure 7 represents photographic images of the fibrin matrix micrograph of a cross-section of the body obtained in FF25 at 200xg / 10min with a 20x magnification. where (1) Ά 'bottom of the metallic support; 'B' peripheral region of the fibrin matrix; 'C central region of the matrix; (2) Micrograph with an increase of 100x of the cross section 'C showing areas Cl - fibrils with cell impregnation - and C2 - dense fibrin borders delimiting chambers or spaces; (3) Enlargement of the Cl zone with evident cell and platelet agglomeration in the center of the matrix; 'D' 4, 5 and 6. Magnifications of 10000x, 2,500x and 10000x demonstrating the presence of intact leukocytes and platelets within the three-dimensional network of fibrin and fibers and fibrils with superficial roughness marked by impregnation of exosomes and peptides;
[027] a figura 8 revela imagens de diferenças dimensionais na avaliação macroscópica das matrizes de LPRF obtidas em diferentes angulações. A escala foi padronizada em mm2. A área total dos espécimes obtidos com ângulo de 25° foi 13,6% maior que as observadas em 33°e 45°. Já a zona de peletização foi aproximadamente 37% maior.[027] Figure 8 reveals images of dimensional differences in the macroscopic evaluation of LPRF matrices obtained at different angles. The scale was standardized in mm 2 . The total area of specimens obtained at an angle of 25 ° was 13.6% greater than those observed at 33 ° and 45 °. The pelletizing zone was approximately 37% larger.
DESCRIÇÃO DA INVENÇÃO DESCRIPTION OF THE INVENTION
[028] Com referência aos desenhos ilustrados, a presente patente de invenção se refere à "APERFEIÇOAMENTOS EM CENTRÍFUGA DE ROTOR FIXO PARA PRODUÇÃO DE MATRIZ DE FIBRINA LEUCOPLAQUETÁRIA AUTÓLOGA PARA FINS TERAPÊUTICOS NÃO- TRANSFUSIONAIS", mais precisamente trata-se de centrífuga de rotor fixo (10) para produção de matriz de fibrina leucoplaquetária autóloga para fins terapêuticos não- transfusionais e aplicabilidade em medicina regenerativa. [028] With reference to the illustrated drawings, the present invention patent refers to "IMPROVEMENTS IN FIXED ROTOR CENTRIFUGAL FOR PRODUCTION OF AUTOLOGICAL LEUKPLAQUETARY FIBRINE MATRIX FOR NON-TRANSFUSIONAL THERAPEUTIC PURPOSES", more precisely it is a rotor centrifuge. (10) for the production of an autologous leukoplakelet fibrin matrix for non-transfusion therapeutic purposes and applicability in regenerative medicine.
[029] Segundo a presente invenção, dita centrífuga (10) prevê rotor (11) preso ao motor (Mt) de indução magnética apresenta múltiplos cassetes (12) posicionadores de
tubos (Tb) acondicionadores das amostras de sangue colhidos à vácuo (não ilustradas), dispostos em angulação (a), preferencialmente de 25° gera no sangue uma contenção ao espalhamento celular indiscriminado e orienta sua estratificação seletiva de acordo com a densidade relativa dos elementos sanguíneos. [029] According to the present invention, said centrifuge (10) provides a rotor (11) attached to the magnetic induction motor (Mt) with multiple cassettes (12) positioning devices tubes (Tb) for the storage of blood samples collected in a vacuum (not shown), arranged at an angle (a), preferably at 25 °, it generates in the blood a restraint to the indiscriminate cell scattering and guides its selective stratification according to the relative density of the elements blood.
[030] Associado a angulação (a) de cada tubo acondicionador (Tb) é previsto um ciclo (CL) formado por centrifugação de baixa rotação com redução de torque, sendo indicada, preferencialmente, a baixa rotação com aceleração crescente de 20 a 1570 rpm durante 30 segundos, seguida por uma estabilização na faixa eleita de 1570 que corresponde à força centrífuga relativa de 200 x g por 10 minutos, em seguida é feita a uma desaceleração sem frenagem ao final do ciclo (CL). [030] Associated with the angulation (a) of each conditioning tube (Tb), a cycle (CL) formed by low speed centrifugation with torque reduction is foreseen, preferentially indicating low speed with increasing acceleration from 20 to 1570 rpm for 30 seconds, followed by a stabilization in the chosen range of 1570, which corresponds to the relative centrifugal force of 200 xg for 10 minutes, followed by a deceleration without braking at the end of the cycle (CL).
[031] A associação da angulação (a) e ciclo (CL) configura a força centrífuga relativa que empurra para cima, para a porção de interesse metodológico, o conteúdo de leucócitos e plaquetas promovendo maior aproveitamento do conteúdo celular. A figura 3 demonstra a contagem celular na porção sobrenadante após a separação seletiva por citometria de fluxo utilizando o rotor (11). [031] The association of angulation (a) and cycle (CL) configures the relative centrifugal force that pushes the leukocyte and platelet content upwards, for the portion of methodological interest, promoting greater use of cellular content. Figure 3 shows the cell count in the supernatant after selective separation by flow cytometry using the rotor (11).
[032] É certo que quando o presente invento for colocado em pratica, poderão ser introduzidas modificações no que se refere a certos detalhes de construção e forma, sem que isso implique afastar-se dos princípios fundamentais que estão claramente substanciados no quadro reivindicatório, ficando assim entendido que a terminologia empregada não teve a finalidade de limitação.
[032] It is true that when the present invention is put into practice, modifications may be made with regard to certain details of construction and shape, without this implying departing from the fundamental principles that are clearly substantiated in the claim framework, becoming thus understood that the terminology used was not intended to be limiting.
Claims
1. "APERFEIÇOAMENTOS EM CENTRÍFUGA DE ROTOR FIXO PARA PRODUÇÃO DE MATRIZ DE FIBRINA LEUCOPLAQU ETÁRIA AUTÓLOGA PARA FINS TERAPÊUTICOS NÃO- TRANSFUSIONAIS", mais precisamente trata-se de centrífuga de rotor fixo (10) para produção de matriz de fibrina leucoplaquetária autóloga para fins terapêuticos não- transfusionais e aplicabilidade em medicina regenerativa; caracterizado por centrífuga (10) prever rotor (11) preso ao motor (Mt) de indução magnética cujos múltiplos cassetes (12) posicionadores de tubos (Tb) acondicionadores das amostras de sangue colhidos à vácuo são dispostos em angulação (a) de 25°; associado à angulação (a) de cada tubo acondicionador (Tb) é previsto um ciclo (CL) formado por centrifugação de baixa rotação com redução de torque, seguida por uma aceleração crescente e estabilização na faixa de força centrífuga eleita; consta também de uma desaceleração sem frenagem ao final do ciclo (CL). 1. "IMPROVEMENTS IN A FIXED ROTOR CENTRIFUGAL FOR THE PRODUCTION OF AUTOGRAPHIC LEUCOPLAQU FIBRINE MATRIX FOR NON-TRANSFUSIONAL THERAPEUTIC PURPOSES", more precisely, it is a fixed rotor centrifuge (10) for the production of autologous leukoplastic therapy matrix. non-transfusion and applicability in regenerative medicine; characterized by a centrifuge (10) providing a rotor (11) attached to the magnetic induction motor (Mt) whose multiple cassettes (12) tube positioners (Tb) for the storage of blood samples collected in a vacuum are arranged in an angle (a) of 25 ° ; associated with the angulation (a) of each conditioning tube (Tb), a cycle (CL) is provided, formed by low-speed centrifugation with torque reduction, followed by increasing acceleration and stabilization in the chosen centrifugal force range; it also consists of a deceleration without braking at the end of the cycle (CL).
2. "APERFEIÇOAMENTOS EM CENTRÍFUGA DE ROTOR FIXO PARA PRODUÇÃO DE MATRIZ DE FIBRINA LEUCOPLAQUETÁRIA AUTÓLOGA PARA FINS TERAPÊUTICOS NÃO- TRANSFUSIONAIS", de acordo com a reivindicação 1, caracterizado por associação da angulação (a) e ciclo (CL) configurar a força centrífuga relativa que empurra para cima, para a porção de interesse metodológico, o conteúdo de leucócitos e plaquetas para aproveitamento do conteúdo celular. 2. "IMPROVEMENTS IN A FIXED ROTOR CENTRIFUGAL FOR THE PRODUCTION OF AUTOLOGICAL LEUKPLAQUETARY FIBRINE MATRIX FOR NON-TRANSFUSIONAL THERAPEUTIC PURPOSES", according to claim 1, characterized by the association of the angulation (a) and cycle (CL) to configure the relative centrifugal force which pushes up the leukocyte and platelet content for the portion of methodological interest to take advantage of the cellular content.
3. "APERFEIÇOAMENTOS EM CENTRÍFUGA DE ROTOR FIXO PARA PRODUÇÃO DE MATRIZ DE FIBRINA LEUCOPLAQUETÁRIA AUTÓLOGA PARA FINS TERAPÊUTICOS NÃO- TRANSFUSIONAIS", de acordo com a reivindicação 1 e numa opção preferencial, caracterizado por a baixa rotação indicar aceleração crescente de 20 a 1570 rpm durante 30 segundos, seguida por uma estabilização na faixa eleita de 1570 que corresponde à força centrífuga relativa de 200 x g por 10 minutos.
3. "IMPROVEMENTS IN A FIXED ROTOR CENTRIFUGAL FOR THE PRODUCTION OF AUTOLOGICAL LEUKPLAQUETARY FIBRINE MATRIX FOR NON-TRANSFUSIONAL THERAPEUTIC PURPOSES", according to claim 1 and in a preferential option, characterized by the low rotation indicating increasing acceleration from 20 to 1570 rpm during 30 seconds, followed by a stabilization in the chosen range of 1570 that corresponds to the relative centrifugal force of 200 xg for 10 minutes.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BRBR1020190241586 | 2019-11-14 | ||
| BR102019024158-6A BR102019024158A2 (en) | 2019-11-14 | 2019-11-14 | improvements in fixed rotor centrifuges for producing autologous buffy coat fibrin matrix for non-transfusion therapeutic purposes |
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| WO2021092670A1 true WO2021092670A1 (en) | 2021-05-20 |
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| PCT/BR2020/050471 WO2021092670A1 (en) | 2019-11-14 | 2020-11-12 | Improvements made to fixed-rotor centrifuges for producing autologous platelet-rich fibrin matrix for non-transfusion therapeutic purposes |
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| BR (1) | BR102019024158A2 (en) |
| WO (1) | WO2021092670A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4553955A (en) * | 1984-06-01 | 1985-11-19 | Beckman Instruments, Inc. | Multi-angle adapter for fixed angle centrifuge rotor |
| US20200306769A1 (en) * | 2019-03-29 | 2020-10-01 | Fiberlite Centrifuge Llc | Fixed angle centrifuge rotor with tubular cavities and related methods |
-
2019
- 2019-11-14 BR BR102019024158-6A patent/BR102019024158A2/en unknown
-
2020
- 2020-11-12 WO PCT/BR2020/050471 patent/WO2021092670A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4553955A (en) * | 1984-06-01 | 1985-11-19 | Beckman Instruments, Inc. | Multi-angle adapter for fixed angle centrifuge rotor |
| US20200306769A1 (en) * | 2019-03-29 | 2020-10-01 | Fiberlite Centrifuge Llc | Fixed angle centrifuge rotor with tubular cavities and related methods |
Non-Patent Citations (4)
| Title |
|---|
| OLIVEIRA, L. A. ET AL.: "Methodological variations affect the release of VEGF in vitro and fibrinolysis' time from platelet concentrates", PLOS ONE, vol. 15, no. 10, e0240134, October 2020 (2020-10-01), XP055822442, DOI: 10.13 71/journal.pone.0240 134 * |
| OLIVEIRA, L. A.: "Caracterizacao morfologica ultraestrutural da matriz de fibrina leucoplaquetária autóloga em associação com biomateriais xenógeno e aloplastico para enxertia ossea", PROTOCOLO FIBRINS . REV. CATARINENSE IMPLANTODONT, vol. 18, 2018, pages 24 - 33 * |
| OLIVEIRA, L. A.: "Caracterizarao morfológica e bioquimica da fibrina leucoplaquetaria autóloga . Perspectivas na aplicação clinica. Brasilia", TESE (DOUTORADO EM CIENCIAS MEDICAS)- FACULDADE DE MEDICINA, July 2020 (2020-07-01), Brasilia, pages 1 - 221, XP055822433 * |
| THERMO FISHER SCIENTIFIC INC.: "Centrífugas de uso geral Thermo Scientific Sorvall Legend e ST", 2013, pages 19, 20, 21, 24 and 25, Retrieved from the Internet <URL:https://assets.thermofisher.com/TFS-Assets/LED/brochures/BRCFGSORGP-BP-0214.pdf> [retrieved on 20210315] * |
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