WO2015172212A1 - Reabsorbable hybrid device for guided tissue regeneration - Google Patents

Reabsorbable hybrid device for guided tissue regeneration Download PDF

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Publication number
WO2015172212A1
WO2015172212A1 PCT/BR2014/050019 BR2014050019W WO2015172212A1 WO 2015172212 A1 WO2015172212 A1 WO 2015172212A1 BR 2014050019 W BR2014050019 W BR 2014050019W WO 2015172212 A1 WO2015172212 A1 WO 2015172212A1
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tissue regeneration
biological
guided tissue
membranes
compounds
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PCT/BR2014/050019
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French (fr)
Portuguese (pt)
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Aguedo Aragones
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Aguedo Aragones
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00Preparations for dentistry
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/12Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L67/00Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
    • C08L67/04Polyesters derived from hydroxycarboxylic acids, e.g. lactones

Definitions

  • the invention is an absorbable membrane, has clinical application in the regenerative area of biological tissues, in particular, bone tissue. It comprises the association of conventional absorbable membranes available in the dental / regenerative medical market with other chemical or biological compounds giving them better mechanical, biological and physiological qualities in the regeneration of damaged tissues. Therefore, it is a hybrid product with more than one raw material in its composition, which may be polymer + polymer; polymer + organic compounds, polymer + inorganic, natural or synthetic compounds.
  • ROG Guided bone regeneration
  • graft material used in conjunction with graft material, is the most commonly used method for bone augmentation in dental practice. Because bone is a relatively slow-growing tissue, both fibroblasts and epithelial cells have the opportunity to occupy available space more efficiently and build soft connective tissue much faster than bone can grow. Thus, the biological mechanism of ROG is the exclusion of unwanted cells in the space filled by the clot under the membrane. If the occlusive barrier lasts long enough, and if it is not exposed to the oral cavity, there are adequate conditions for stem cells and osteoprogenitor cells to differentiate into osteoblasts, which deposit bone matrix. In other words, the membrane creates a solitary space that allows the bone to use its large natural capacity safely or safely. (BUSER, D.2010)
  • NON-ABSORBABLE MEMBRANES Expanded polytetrafluoroethylene (e-PTFE) membranes are considered the "gold standard" for bone regeneration (TRIPLETT, SCHOW, FIELD 2001).
  • e-PTFE Expanded polytetrafluoroethylene
  • Polymer-derived membranes may be classified as absorbable when produced from polylactic and polyglycolic acids and not absorbable when produced from expanded or non-expanded polytetrafluoroethylene.
  • Polyglycolic acid (PGA) exhibits good mechanical properties and its main use is as a support material.
  • Lactic acid-derived poly L-lactic acid (PLLA) has high strength, thermoplastic behavior, biocompatibility, and water sensitivity as they degrade slowly compared to water-soluble polymers.
  • the polylactic-co-glycolic acid (PLGA) copolymer a combination of polylactic and polyglycolic acid, requires less time for complete degradation and its chemical structure is more susceptible to hydrolysis reaction as it has a lower impediment to molecule attack. of water. (TATAKIS, PROMSUDTHI, WIKESJO2000).
  • the fusion Polymers is a good way to obtain a material with the desired properties.
  • the combination exhibits advantages in physical and chemical properties, which are not observed in polymers individually.
  • EP 0271831 A2 US5077049 A, US6251419 B1, US4981707, W01990007308 A1, WQ1990000410A1, and US6031 148 A describe polymer derived membranes related to the object described in this report.
  • the present invention utilizes absorbable membrane technology added to other compounds for the purpose of stimulating new tissue formation and increasing mechanical strength.
  • the hybrid membrane described in this report is characterized by the use of the best qualities of each component of the mixture in regenerative processes.
  • the manufacturing process of hybrid membranes follows different formulations according to the desired characteristics in the products. The degradation and resorption time of the new membranes depends on the parameters of the manufacturing process. At Their mechanical characteristics are also associated with the manufacturing process.
  • the invention has as its basic principle the use of the best membrane properties (filter / barrier) with the properties of the materials used as graft (calcium phosphates, collagen type I, II or III).
  • the advantage is the biological and mechanical characteristics that are added to the absorbable membranes.
  • the presence of a material capable of inducing new tissue formation in the membrane composition accelerates the new tissue formation process and reduces patient recovery time.
  • the advantages of the invention add to the advantages of absorbable polymer based products (no second surgical removal required, biodegradable, controllable resorption time, no metabolic residue, degraded by hydrolysis).
  • membranes also have, there is also controlled release of the agents inductors added to the physical structure of these membranes. Initially, they perform the same function as other membranes on the market, but with great differential of greater rigidity and greater mechanical resistance allowing to withstand mechanical forces in all directions, due to the presence of these substances.
  • the present invention has as its main differential the release of the second component, or "load”, of the membrane at a second moment.
  • the polymer which acts as a “matrix”
  • the release of the "active charge” that comes to play a new biological function.
  • RMG Guided Tissue Regeneration
  • the second phase (charge) is added at the time of membrane preparation.
  • the matrix-forming copolymers are completely diluted in organic solvent. Thereafter, additional second phase compounds (filler), as needed, are added to the copolymer in different concentrations according to application, ranging from 0.0001% to 99.9999%.
  • the mixture is poured into containers of the desired volume to form, upon drying, films or membranes of varying thicknesses ranging from 0.0001 mM to 10 mM.
  • copolymers are degraded in vivo by hydrolysis when in contact with body fluids generating products that are metabolized by the body to CO 2 and H 2 O. Simultaneously to biodegradation occurs the release of the "charge” added to the copolymer allowing physiological action according to its chemical and biological properties.
  • Membranes act as mechanical barriers that prevent the migration of epithelial tissue and gingival connective tissue to the defect area, maintaining space between the membrane and bone, allowing for cell re-population, bone maturation and defect regeneration. Because it is absorbable, the use of this membrane eliminates the need for a second surgery to remove it. Because they are "loaded" with bioactive substances, at the moment of degradation occurs the release of these substances in the tissues, producing the desired physiological effect.
  • Matrix Copolymer of polylactic acid with polyglycolic acid.
  • ITS MANUFACTURING VARIANTS Matrix and Load
  • Matrix The copolymer of polylactic acid and polyglycolic acid may vary in proportion from each of 99/01 to 01/99.
  • the concentration of mechanical or bioactive agents may range from 0.0001% to 99.9999%.
  • Matrix Variations in the proportions of polylactic and polyglycolic acid polymers produce different mechanical and biological characteristics. Increasing the polyglycolic proportion increases the degradation and reduces the degradation time of the copolymer. On the other hand, the increase of the polylactic gives an increase of the mechanical flexural strength, conferring better mechanical properties.

Abstract

The reabsorbable hybrid device for guided tissue regeneration describes an absorbable, implantable synthetic membrane designed for use as a biological barrier in guided tissue regeneration (GTR) procedures in the treatment of periodontal and bone defects, which forms a biological barrier composed of poly(lactic-co-glycolic acid) copolymers that acts as a matrix, and a second phase that acts as filler and/or biological inducers; and the copolymers that form the matrix are completely diluted in organic solvent followed by the addition of the additional compounds of the second phase (filler), as required, in various concentrations in accordance with use, potentially ranging from 0.0001% to 99.9999%.

Description

Dispositivo Híbrido Reabsorvível para Regeneração Tecidual Guiada  Resorbable Hybrid Device for Guided Tissue Regeneration
[001 ] A invenção é uma membrana absorvível, tem a aplicação clínica na área regenerativa dos tecidos biológicos, em especial, tecido ósseo. Compreende a associação de membranas absorvíveis convencionais disponíveis no mercado odonto/médico regenerativo, a outros compostos químicos ou biológicos conferindo-lhes melhores qualidades mecânicas, biológicas e fisiológicas na regeneração de tecidos lesados. Portanto, se trata de um produto híbrido com mais de uma matéria prima na sua composição, podendo ser polímero + polímero; polímero + compostos orgânicos, polímero + compostos Inorgânicos, naturais ou sintéticos.  [001] The invention is an absorbable membrane, has clinical application in the regenerative area of biological tissues, in particular, bone tissue. It comprises the association of conventional absorbable membranes available in the dental / regenerative medical market with other chemical or biological compounds giving them better mechanical, biological and physiological qualities in the regeneration of damaged tissues. Therefore, it is a hybrid product with more than one raw material in its composition, which may be polymer + polymer; polymer + organic compounds, polymer + inorganic, natural or synthetic compounds.
[002] A regeneração óssea guiada (ROG), usada em conjunto com o material de enxerto, é o método mais usado para o aumento ósseo na prática odontológica. Já que o osso é um tecido de crescimento relativamente lento, tanto fibroblastos como células epiteliais têm a oportunidade de ocupar o espaço disponível com mais eficiência e construir um tecido conjuntivo mole muito mais rápido do que o osso é capaz de crescer. Assim, o mecanismo biológico da ROG é a exclusão de células indesejáveis no espaço preenchido pelo coágulo sob a membrana. Se a barreira oclusiva durar o suficiente, e se esta não for exposta à cavidade bucal, existem condições adequadas para as células-tronco e células osteoprogenitoras diferenciarem-se em osteoblastos, que depositam matriz óssea. Em outras palavras, a membrana cria um espaço solitário que permite ao osso usar sua grande capacidade natural de modo seguro ou protegido. (BUSER, D.2010)  Guided bone regeneration (ROG), used in conjunction with graft material, is the most commonly used method for bone augmentation in dental practice. Because bone is a relatively slow-growing tissue, both fibroblasts and epithelial cells have the opportunity to occupy available space more efficiently and build soft connective tissue much faster than bone can grow. Thus, the biological mechanism of ROG is the exclusion of unwanted cells in the space filled by the clot under the membrane. If the occlusive barrier lasts long enough, and if it is not exposed to the oral cavity, there are adequate conditions for stem cells and osteoprogenitor cells to differentiate into osteoblasts, which deposit bone matrix. In other words, the membrane creates a solitary space that allows the bone to use its large natural capacity safely or safely. (BUSER, D.2010)
[003] A doença periodontal traz danos muitas vezes irreversíveis aos tecidos periodontais e principalmente ao tecido ósseo. A reabsorção alveolar leva a uma perda de suporte que compromete a inserção do implante e isso traz problemas tanto no pré quanto trans e pós-operatórios. Uma das soluções viáveis e previsíveis para problemas de reabsorções ou falta de tecido ósseo, o que promove a deiscência, é a utilização de osso para enxerto (autógeno ou não) juntamente com membranas. As pesquisas que avaliaram aumento ósseo em implantes de titânio usando enxerto autógeno e barreiras reabsorvíveis em tíbia de coelhos demonstraram que no período de cicatrização de 12 semanas, analisadas histomorfometricamente, o aumento do volume ósseo é significativo; mas há diferença na quantidade de osso mineralizado. Os autores concluíram que as partículas de enxerto de osso autógeno recobertos com membranas reabsorvíveis resultaram em maior volume de osso que o uso de enxertos não cobertos com barreira. (BUSER, D 2010) (NYMAN. 1994) Periodontal disease causes often irreversible damage to periodontal tissues and especially bone tissue. Alveolar Resorption leads to a loss of support that compromises implant insertion and this causes problems both pre and trans and postoperatively. One of the viable and predictable solutions to resorption problems or lack of bone tissue, which promotes dehiscence, is the use of graft bone (autogenous or not) together with membranes. Research evaluating bone augmentation in titanium implants using autogenous grafting and resorbable barriers in rabbit tibia has shown that over the 12-week healing period, histomorphometrically analyzed, bone volume increase is significant; but there is a difference in the amount of mineralized bone. The authors concluded that autogenous bone graft particles coated with resorbable membranes resulted in larger bone volume than the use of unbarred grafts. (BUSER, D 2010) (NYMAN, 1994)
[004] Dentre as características básicas de uma membrana utilizada como barreira, podemos citar: a capacidade de formação e manutenção do espaço para manter um volume e geometria espacial suficiente no período de reparo e a biocompatibilidade, que é a capacidade do material de desempenhar sua função especifica, sem causar reações adversas locais e sistémicas por parte do hospedeiro, bem como os produtos finais da degradação das membranas reabsorvíveis devem ser inertes. (IGNATIUS, CLAES 1996). Além disso, a facilidade no manejo clínico das membranas durante os procedimentos cirúrgicos deve ser avaliada na escolha do material a ser utilizado. (DAHLINeí al 1990).  [004] Among the basic characteristics of a membrane used as a barrier, we can mention: the capacity of formation and maintenance of space to maintain a sufficient volume and spatial geometry during the repair period and the biocompatibility, which is the ability of the material to perform its function. specific function, without causing local and systemic adverse reactions by the host, as well as the end products of the resorbable membrane degradation must be inert. (IGNATIUS, CLAES 1996). In addition, the ease of clinical management of the membranes during surgical procedures should be evaluated when choosing the material to be used. (DAHLINE et al. 1990).
[005] As membranas disponíveis no mercado podem ser divididas em NÃO ABSORVÍVEIS e ABSOVÍVEIS. [0061 MEMBRANAS NÃO ABSORVÍVEIS: As membranas de politetrafluoretileno expandido (e-PTFE) são consideradas o "padrão ouro" para regeneração óssea (TRIPLETT, SCHOW, FIELD 2001 ). Porém, o fato destas membranas não serem absorvíveis faz com que o tratamento seja mais traumático, visto que se torna necessário um segundo tempo cirúrgico para a remoção da mesma, além disso, é comum deiscência da sutura e posterior infecção na região em que se deseja o reparo (SIMOM et al 1999). Entre os principais fabricantes: GoreTex: h tt :/ w . q o ?e rr edicai. co m/ reg en m e m bran β·' Commercially available membranes can be divided into NON-ABSORBABLE and ABSOVABLE. NON-ABSORBABLE MEMBRANES: Expanded polytetrafluoroethylene (e-PTFE) membranes are considered the "gold standard" for bone regeneration (TRIPLETT, SCHOW, FIELD 2001). However, the fact that these membranes are not absorbable makes the treatment more traumatic, since a second surgical time is necessary to remove it, and suture dehiscence and subsequent infection in the desired region are common. the repair (SIMOM et al 1999). Among the leading manufacturers: GoreTex: h tt: / w. what? and rr edit. co m / reg in mem bran β · '
[007] Assim, pesquisas utilizando novos e melhorados materiais absorvíveis estão sendo desenvolvidas para alcançar resultados semelhantes ou melhores do que encontrados com as membranas não absorvíveis. (PETITE 2000; PEREIRA ET AL 2000; CHEN et a/2072; JUNG et al 2012).  Thus research using new and improved absorbable materials is being developed to achieve results similar to or better than those found with nonabsorbable membranes. (PETITE 2000; PEREIRA ET AL 2000; CHEN et al / 2072; JUNG et al 2012).
Í0081 MEMBRANAS ABSORVÍVEIS: As membranas derivadas de polímeros podem ser classificadas em absorvíveis, quando produzidas a partir dos ácidos polilático e poliglicólico, e não absorvíveis quando produzida em politetrafluoretileno expandido ou não. Ácido poliglicólico (PGA) exibe boas propriedades mecânicas e seu principal uso é como material de suporte. O ácido poli L-láctico (PLLA) derivado do ácido láctico possui alta resistência, comportamento termoplástico, biocompatibilidade e sensibilidade à água, visto que degradam-se lentamente, quando comparados aos polímeros solúveis que aumentam de volume na água. O copolímero de ácido polilático-co-glicólico (PLGA), uma combinação do ácido polilático e poliglicólico, requer um menor tempo para sua completa degradação e sua estrutura química é mais suscetível à reação de hidrólise, pois possui um impedimento menor ao ataque das moléculas de água. (TATAKIS, PROMSUDTHI, WIKESJO2000). A fusão de polímeros é um bom caminho para a obtenção de um material com as propriedades desejadas. A combinação exibe vantagens nas propriedades físicas e químicas, as quais não são observadas nos polímeros individualmente. ABSORBABLE MEMBRANES: Polymer-derived membranes may be classified as absorbable when produced from polylactic and polyglycolic acids and not absorbable when produced from expanded or non-expanded polytetrafluoroethylene. Polyglycolic acid (PGA) exhibits good mechanical properties and its main use is as a support material. Lactic acid-derived poly L-lactic acid (PLLA) has high strength, thermoplastic behavior, biocompatibility, and water sensitivity as they degrade slowly compared to water-soluble polymers. The polylactic-co-glycolic acid (PLGA) copolymer, a combination of polylactic and polyglycolic acid, requires less time for complete degradation and its chemical structure is more susceptible to hydrolysis reaction as it has a lower impediment to molecule attack. of water. (TATAKIS, PROMSUDTHI, WIKESJO2000). The fusion Polymers is a good way to obtain a material with the desired properties. The combination exhibits advantages in physical and chemical properties, which are not observed in polymers individually.
[009] Principais fabricantes: INION htt ,:/ ^^  [009] Top Manufacturers: INION htt,: / ^^
Bionnovation: htip www. ;onnovaiion.comi)r/¾urglt;me.htrni Bionnovation: htip www. ; onnovaiion.comi) r / glurglt; me.htrni
[010] O documentos de patente: EP0271831 A2, US5077049 A, US6251419 B1 , US4981707, W01990007308 A1 , WQ1990000410A1 , e US6031 148 A descrevem membranas derivadas de polímeros, relacionada ao objeto descrito neste relatório.  EP 0271831 A2, US5077049 A, US6251419 B1, US4981707, W01990007308 A1, WQ1990000410A1, and US6031 148 A describe polymer derived membranes related to the object described in this report.
[01 1 ] Portanto, tanto as membranas absorvíveis como as "não absorvíveis" executam uma função de barreira biológica. A diferença básica é na necessidade de uma segunda cirurgia para retirada das membranas "não absorvíveis".  [01 1] Therefore, both absorbable and non-absorbable membranes perform a biological barrier function. The basic difference is the need for a second surgery to remove "non-absorbable" membranes.
[012] Atualmente, os materiais absorvíveis disponíveis para execução da técnica cirúrgica não estão associados.  [012] Currently, the absorbable materials available for performing the surgical technique are not associated.
[013] BREVE DESCRIÇÃO DA INVENÇÃO - A presente invenção utiliza a tecnologia das membranas absorvíveis adicionadas a outros compostos com objetivo de estimular a formação do novo tecido e aumentar a resistência mecânica. A membrana híbrida, descrita neste relatório, tem como característica a utilização das melhores qualidades de cada componente da mistura nos processos regenerativos. O processo de fabricação das membranas híbridas obedece às diferentes formulações de acordo com as características desejadas nos produtos. O tempo de degradação e reabsorção das novas membranas depende dos parâmetros do processo de fabricação. As características mecânicas das mesmas também estão associadas ao processo de fabricação. BRIEF DESCRIPTION OF THE INVENTION The present invention utilizes absorbable membrane technology added to other compounds for the purpose of stimulating new tissue formation and increasing mechanical strength. The hybrid membrane described in this report is characterized by the use of the best qualities of each component of the mixture in regenerative processes. The manufacturing process of hybrid membranes follows different formulations according to the desired characteristics in the products. The degradation and resorption time of the new membranes depends on the parameters of the manufacturing process. At Their mechanical characteristics are also associated with the manufacturing process.
[014] A invenção tem como princípio básico a utilização das melhores propriedades das membranas (filtro/barreira) com as propriedades dos materiais utilizados como enxerto (fosfatos de cálcio, colágeno tipo I, II ou III ).  [014] The invention has as its basic principle the use of the best membrane properties (filter / barrier) with the properties of the materials used as graft (calcium phosphates, collagen type I, II or III).
[015] Destacam-se como vantagem as características biológicas e mecânicas que são acrescentadas às membranas absorvíveis. A presença de um material capaz de induzir a formação de novo tecido na composição da membrana acelera o processo de formação do novo tecido e reduz o tempo de recuperação do paciente.  The advantage is the biological and mechanical characteristics that are added to the absorbable membranes. The presence of a material capable of inducing new tissue formation in the membrane composition accelerates the new tissue formation process and reduces patient recovery time.
[016] No caso da adição ao polímero absorvível de uma biocerâmica (fosfato de cálcio) o mecanismo de ação ocorre com a liberação de partículas de fosfato de cálcio ao meio fisiológico à medida que o polímero sofre a biodegradação. Essas partículas de fosfato de cálcio no meio do tecido vão estimular as células daquela região a formar o novo tecido ósseo, caso seja essa a necessidade. Para aplicação e regeneração de outros tecidos a substância indutora selecionada deve ser de acordo com o tecido a ser regenerado.  [016] In the case of the addition to the absorbable polymer of a bioceramic (calcium phosphate) the mechanism of action occurs with the release of calcium phosphate particles to the physiological medium as the polymer undergoes biodegradation. These calcium phosphate particles in the middle of the tissue will stimulate cells in that region to form new bone tissue, should the need arise. For application and regeneration of other tissues the selected inducing substance should be in accordance with the tissue to be regenerated.
• · • ·
Polímero absorvível + Substância Indutora = Membrana Bioativa Absorbable Polymer + Inducing Substance = Bioactive Membrane
[017] As vantagens da invenção se somam às vantagens dos produtos a base de polímeros absorvíveis (não requer segunda intervenção cirúrgica para remoção, são biodegradáveis, tempo de reabsorção controlável, não há resíduo metabólico, degradados por hidrólise). Além dessas vantagens que as membranas também possuem, há ainda a liberação controlada dos agentes indutores adicionados na estrutura física dessas membranas. Inicialmente, elas executam a mesma função das demais membranas do mercado, porém com grande diferencial de maior rigidez e maior resistência mecânica permitindo suportar esforços mecânicos em todas as direções, isso pela presença dessas substâncias. [017] The advantages of the invention add to the advantages of absorbable polymer based products (no second surgical removal required, biodegradable, controllable resorption time, no metabolic residue, degraded by hydrolysis). In addition to these advantages that membranes also have, there is also controlled release of the agents inductors added to the physical structure of these membranes. Initially, they perform the same function as other membranes on the market, but with great differential of greater rigidity and greater mechanical resistance allowing to withstand mechanical forces in all directions, due to the presence of these substances.
[018] Outra grande, e exclusiva, vantagem a ser destacada, é a liberação dos componentes adicionados, sejam eles biológicos ou químicos. Tal liberação ocorre após a primeira fase funcional de "barreira/filtro" da membrana. No momento da estruturação e formação do novo tecido a presença de substâncias indutoras acelera o processo regenerativo.  [018] Another major and unique advantage to be highlighted is the release of added components, whether biological or chemical. Such release occurs after the first functional "barrier / filter" phase of the membrane. At the time of structuring and formation of the new tissue the presence of inducing substances accelerates the regenerative process.
[019] Portanto, a presente invenção tem como principal diferencial a liberação do segundo componente, ou "carga", da membrana num segundo momento. Durante a reabsorção do polímero, que atua como uma "matriz" há a liberação da "carga ativa" que vem desempenhar uma nova função biológica. DESCRIÇÃO DETALHADA DA INVENÇÃO  Therefore, the present invention has as its main differential the release of the second component, or "load", of the membrane at a second moment. During resorption of the polymer, which acts as a "matrix", there is the release of the "active charge" that comes to play a new biological function. DETAILED DESCRIPTION OF THE INVENTION
[020] Trata-se de uma membrana sintética, implantável, absorvível projetada para uso como barreira biológica em procedimentos de Regeneração Tecidual Guiada (RTG) no tratamento de defeitos periodontais e ósseos.  [020] It is a synthetic, implantable, absorbable membrane designed for use as a biological barrier in Guided Tissue Regeneration (RTG) procedures in the treatment of periodontal and bone defects.
[021 ] É uma barreira biológica composta por copolímeros de ácido polilático e poliglicólico que atua como uma matriz, e uma segunda fase, que atua como carga e/ou indutores biológicos. A segunda fase (carga) é acrescentada no momento da preparação das membranas.  [021] It is a biological barrier composed of polylactic and polyglycolic acid copolymers that acts as a matrix, and a second phase, which acts as a charge and / or biological inductors. The second phase (charge) is added at the time of membrane preparation.
[022] Inicialmente, os copolímeros que formam a matriz são completamente diluídos em solvente orgânico. Após isso, os compostos adicionais da segunda fase (carga), conforme a necessidade, são acrescentados ao copolímero em concentrações diversas conforme aplicação, podendo variar de 0,0001 % até 99,9999%. Initially, the matrix-forming copolymers are completely diluted in organic solvent. Thereafter, additional second phase compounds (filler), as needed, are added to the copolymer in different concentrations according to application, ranging from 0.0001% to 99.9999%.
[023] A mistura é vazada em recipientes de acordo com o volume desejado de modo a formar, após a secagem, filmes ou membranas com espessuras diversas que podem variar de 0,0001 mM até 10 mM.  [023] The mixture is poured into containers of the desired volume to form, upon drying, films or membranes of varying thicknesses ranging from 0.0001 mM to 10 mM.
[024] Esses copolímeros (matriz) são degradados in vivo por hidrólise quando em contato com fluidos corpóreos gerando produtos que são metabolizados pelo organismo até CO2 e H2O. Simultaneamente à biodegradação ocorre a liberação da "carga" adicionada ao copolímero permitindo a ação fisiológica da mesma de acordo com as suas propriedades químicas e biológicas. [024] These copolymers (matrix) are degraded in vivo by hydrolysis when in contact with body fluids generating products that are metabolized by the body to CO 2 and H 2 O. Simultaneously to biodegradation occurs the release of the "charge" added to the copolymer allowing physiological action according to its chemical and biological properties.
[025] As membranas atuam como barreiras mecânicas que impedem a migração de tecido epitelial e tecido conjuntivo gengival para a área do defeito, mantendo espaço entre a membrana e o osso, permitindo que haja re- população celular, maturação óssea e regeneração do defeito. Por ser absorvível, o uso dessa membrana elimina a necessidade de uma segunda cirurgia para retirada da mesma. Por estarem "carregadas" com substâncias bioativas, no momento da degradação ocorre a liberação dessas substâncias no meio dos tecidos produzindo o efeito fisiológico desejado.  [025] Membranes act as mechanical barriers that prevent the migration of epithelial tissue and gingival connective tissue to the defect area, maintaining space between the membrane and bone, allowing for cell re-population, bone maturation and defect regeneration. Because it is absorbable, the use of this membrane eliminates the need for a second surgery to remove it. Because they are "loaded" with bioactive substances, at the moment of degradation occurs the release of these substances in the tissues, producing the desired physiological effect.
[026] DESCRIÇÃO DOS COMPONENTES - As membranas sintéticas absorvíveis bioativas são formadas por 2 componentes:  [026] COMPONENT DESCRIPTION - Bioactive absorbable synthetic membranes consist of 2 components:
1 ) Matriz: Copolímero de ácido polilático com ácido poliglicólico.  1) Matrix: Copolymer of polylactic acid with polyglycolic acid.
2) Carga: Substâncias ou Compostos Químicos ou Biológicos que conferem características mecânicas e biológicas "Bioativa".  2) Cargo: Chemical or Biological Substances or Compounds that confer mechanical and biological characteristics "Bioactive".
[027] SUAS VARIANTES NA FABRICAÇÃO: matriz e carga [028] Matriz: O copolímero de ácido polilático e ácido poliglicólico pode variar na proporção de cada um desde 99/01 até 01 /99. [027] ITS MANUFACTURING VARIANTS: Matrix and Load [028] Matrix: The copolymer of polylactic acid and polyglycolic acid may vary in proportion from each of 99/01 to 01/99.
[029] Carga: A concentração dos agentes mecânicos ou bioativos pode variar desde 0,0001 % até 99,9999%.  Load: The concentration of mechanical or bioactive agents may range from 0.0001% to 99.9999%.
[030] SUAS VARIANTES NA FUNCIONALIDADE: matriz e carga  [030] YOUR VARIANTS IN FUNCTIONALITY: Matrix and Charge
[031 ] Matriz: As variações nas proporções dos polímeros ácidos polilático e poliglicólico produzem características mecânicas e biológicas diferentes. O aumento do poliglicólico na proporção produz um aumento da degradação e redução do tempo de degradação do copolímero. Por outro lado, o aumento do polilático confere um aumento da resistência mecânica à flexão, conferindo melhores propriedades mecânicas.  [031] Matrix: Variations in the proportions of polylactic and polyglycolic acid polymers produce different mechanical and biological characteristics. Increasing the polyglycolic proportion increases the degradation and reduces the degradation time of the copolymer. On the other hand, the increase of the polylactic gives an increase of the mechanical flexural strength, conferring better mechanical properties.
[032] Carga: caso a carga seja uma biocerâmica (fosfato de cálcio), o aumento da proporção dessa produz maior rigidez e melhora a resistência mecânica à flexão e compressão até um limite de 99% da mistura. O efeito biológico das biocerâmicas estão relacionados a presença dos íons cálcio e de fosfatos no meio fisiológico. A porção mais cristalina, chamada de hidroxiapatita, tem uma reabsorção muito lenta, o que lhe confere uma propriedade mecânica de preenchimento de defeitos e manutenção de arcabouços biológicos para auxiliar na regeneração do tecido lesado. A porção mais "solúvel" da biocerâmica, chamada de beta Trifosfato de Cálcio, possui uma solubilidade maior, o que resulta na liberação dos íons Cálcio e Fósforo, necessários na regeneração do tecido ósseo.  [032] Load: If the load is a bioceramic (calcium phosphate), increasing its proportion produces greater stiffness and improves mechanical flexural and compressive strength to a limit of 99% of the mixture. The biological effect of bioceramics is related to the presence of calcium and phosphate ions in the physiological environment. The most crystalline portion, called hydroxyapatite, has a very slow resorption, which gives it a mechanical defect-filling property and maintenance of biological frameworks to assist in the regeneration of damaged tissue. The most "soluble" portion of bioceramics, called beta calcium triphosphate, has a higher solubility, which results in the release of calcium and phosphorus ions, which are necessary for bone tissue regeneration.
[033] No caso da carga ser um indutor bioquímico há uma relação de dose/efeito para cada droga, devendo essa proporção ser validada de acordo com as normas de ensaios pré-definidos pelos órgãos reguladores.  [033] In the case that the load is a biochemical inducer, there is a dose / effect relationship for each drug and this ratio should be validated according to test standards predefined by regulatory agencies.

Claims

REIVINDICAÇÕES
1 . Dispositivo Híbrido Reabsorvível para Regeneração Tecidual Guiada é uma membrana sintéticas absorvíveis bioativas, com aplicação clínica na área regenerativa dos tecidos biológicos, em especial, tecido ósseo que compreende a associação de membranas absorvíveis convencionais disponíveis no mercado odonto/médico regenerativo, a outros compostos químicos ou biológicos, caracterizado pelas membranas sintéticas absorvíveis bioativas serem formadas por 2 componentes: a Matriz, que é um Copolímero de ácido polilático com ácido poliglicolico, e a Carga, que é constituída por Substâncias ou Compostos Químicos ou Biológicos Bioativas;  1 . Hybrid Resorbable Device for Guided Tissue Regeneration is a bioactive absorbable synthetic membrane with clinical application in the regenerative area of biological tissues, in particular bone tissue comprising the association of conventional absorbable membranes available in the dental / regenerative market with other chemical compounds or Biological, characterized in that the bioactive absorbable synthetic membranes are formed by 2 components: the Matrix, which is a polylactic acid copolymer with polyglycolic acid, and the Charge, which is composed of Bioactive Chemical or Biological Substances or Compounds;
2. Dispositivo Híbrido Reabsorvível para Regeneração Tecidual Guiada, de acordo com a reivindicação 1 , caracterizado pelo copolímero de ácido polilático e ácido poliglicolico poder variar na proporção de cada um desde 99/01 até 01/99;  Resorbable Hybrid Guided Tissue Regeneration Device according to Claim 1, characterized in that the copolymer of polylactic acid and polyglycolic acid may vary in proportion from 99/01 to 01/99;
3. Dispositivo Híbrido Reabsorvível para Regeneração Tecidual Guiada, de acordo com a reivindicação 1 , caracterizado pela concentração das Substâncias ou Compostos Químicos ou Biológicos Bioativas poder variar desde 0,001 % até 99,999%;  Resorbable Hybrid Guided Tissue Regeneration Device according to Claim 1, characterized in that the concentration of the Bioactive Chemical or Biological Substances or Compounds can range from 0.001% to 99.999%;
4. Dispositivo Híbrido Reabsorvível para Regeneração Tecidual Guiada, de acordo com a reivindicação 1 , caracterizado pelas Substâncias ou Compostos Químicos ou Biológicos Bioativas ser a base de fosfato de cálcio, até um limite de 99% da mistura;  Resorbable Hybrid Guided Tissue Regeneration Device according to Claim 1, characterized in that the Bioactive Chemical or Biological Substances or Compounds are calcium phosphate based up to a limit of 99% of the mixture;
5. Método de obtenção do Dispositivo Híbrido Reabsorvível para Regeneração Tecidual Guiada reivindicado na reivindicação 1 , caracterizado por compreender: • Diluir inicialmente os copolímeros que formam a matriz em solvente orgânico. Method for obtaining the Resorbable Hybrid Guided Tissue Regeneration Device claimed in claim 1, characterized in that it comprises: • First dilute the matrix-forming copolymers in organic solvent.
• Após isso, os compostos adicionais da segunda fase (carga), conforme a necessidade, serem acrescentados ao copolímero em concentrações diversas conforme aplicação, podendo variar de 0,0001 % até 99,9999%.  • After that, additional second phase (filler) compounds, as required, may be added to the copolymer in varying concentrations as applied, ranging from 0.0001% to 99.9999%.
• Vazar a mistura em recipientes de acordo com o volume desejado de modo a formar, após a secagem, filmes ou membranas com espessuras diversas que podem variar de 0,0001 mM até 10 mM.  • Pour the mixture into containers to the desired volume to form, after drying, films or membranes of varying thicknesses ranging from 0.0001 mM to 10 mM.
• Degradar in vivo por hidrólise os copolímeros, que forma a matriz, quando em contato com fluidos corpóreos.  • Degrade in vivo by hydrolysis the copolymers forming the matrix when in contact with body fluids.
• Ocorrer, simultaneamente à biodegradação, a liberação da "carga" adicionada ao copolímero.  • At the same time as biodegradation occurs, the release of the "charge" added to the copolymer.
PCT/BR2014/050019 2014-05-15 2014-11-24 Reabsorbable hybrid device for guided tissue regeneration WO2015172212A1 (en)

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