WO2011000071A1 - Procédé de fabrication de membrane de collagène biocompatible à application médico-odontologique et produit ainsi obtenu - Google Patents

Procédé de fabrication de membrane de collagène biocompatible à application médico-odontologique et produit ainsi obtenu Download PDF

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Publication number
WO2011000071A1
WO2011000071A1 PCT/BR2010/000221 BR2010000221W WO2011000071A1 WO 2011000071 A1 WO2011000071 A1 WO 2011000071A1 BR 2010000221 W BR2010000221 W BR 2010000221W WO 2011000071 A1 WO2011000071 A1 WO 2011000071A1
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WO
WIPO (PCT)
Prior art keywords
process according
hours
raw material
stretching
detergent
Prior art date
Application number
PCT/BR2010/000221
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English (en)
Portuguese (pt)
Inventor
Benedicto De Campos Vidal
Ariel Lenharo
Original Assignee
Agência De Inovação-Inova
Priority date (The priority date 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 date listed.)
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Publication date
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Publication of WO2011000071A1 publication Critical patent/WO2011000071A1/fr

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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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking

Definitions

  • the present invention relates to a process for obtaining a collagen membrane consisting of type I collagen for medical and dental application.
  • the obtained membrane acts as a barrier in dental surgeries, in which it is desired to form bone tissue, preferably to fibrous tissue. In addition, it can be used in surgeries where it is desired to protect bone graft material.
  • biomembranes perform the following functions: restore the vapor barrier and prevent wound dehydration; decrease evaporation by heat loss; prevent bacterial contamination by protecting the wound and the patient from septicemia; allow less painful dressing changes; facilitate wound debridement and improve the quality of healing.
  • the biomembrane can still be used in urogenital, colon and rectum, stomach, obstetrics and gynecology, otorhinolaryngology, plastic surgery, urology, vascular surgery,
  • the application of the present invention may be used as a dressing to aid in the treatment of burns. It may also be used in cases of urogenital surgeries, such as for the placement of urethral bands for the treatment of urinary incontinence and pelvic reconstruction. repair of wall defects, including ventral and inguinal hernias.
  • ROG Guided Bone Regeneration
  • non-resorbable barriers were used in RTG.
  • the first commercially available RTG barrier was manufactured from expanded polytetrafluoroethylene (Gore-Tex ® , Periodontal Material, WL Gore & Associates, Flagstaff).
  • Resorbable barriers have been evaluated regarding their safety and their role as a barrier in tissue regeneration, such as collagen, polylactic acid, polyglycolic lactic acid. Resorbable barriers are of great interest because they do not require a second surgical act to remove them. Avoiding this second surgical procedure has the benefit for the patient of not having a second surgery and eliminating surgical trauma in new and immature periodontal tissue that has been regenerated. (Wang and McNeil, 1998)
  • collagen has deserved prominence, as it constitutes one of the main components of the extra-cellular matrix of periodontal connective tissue.
  • it is physiologically metabolized, fibroblast chemotactic, hemostatic, has poor immunogenicity, and functions as a carrier for cell migration (Blumenthal, 1988; Pitaru et al., 1887).
  • Collagen is the main structural protein of vertebrate tissues and the most abundant of connective tissue and can be found in the skin, bones, tendons and teeth. In bone tissue corresponds to 90% of the organic portion of this. Its main feature is the formation of insoluble fibers with high tensile strength.
  • Collagen is considered one of the most useful biomaterials. Due to its physicochemical properties (presence or addition of crosslinking or variable cross-linking controlling the degree of imbibition and resorption), physicomechanical (interlacing or fiber orientation) and biocompatibility (low allergenicity) collagen is widely used. as implant material both in the form pure as gel (Friess, 2001) or associated with other molecules such as polysaccharides, biological and microbial (De Paula et al, 2002).
  • collagen and its degradation products are recognized by various studies found in the literature as recognized by various cell types and thus leading to phenomena of cell adhesion, growth and cell differentiation.
  • Another feature of collagen is that it can be associated with synthetic materials, proving to be a versatile protein in terms of chemical reactivity, allowing the introduction of quite varied chemical, physicochemical, biological and mechanical properties.
  • collagen has hemostatic function, surgical wound stabilization, semipermeability, allowing nutrient passage, natural enzymatic degradation, and fibroblast chemotactic ability (Postlethwaite et al., 1978).
  • Collagen membranes obtained by the proposed procurement process, are mechanically malleable, adaptable and easy to manipulate, which is beneficial in clinical application.
  • the collagen membrane for tissue barrier in RTG used in this study is obtained from the porcine and or bovine intestinal submucosa. Numerous research in various areas of medicine (urology, gastroenterology, dermatology, orthopedics, immunology, cardiology, dentistry, bioengineering of tissues) has shown that this is a versatile and efficient source, as well as not triggering antigenic responses in the receptor. able to function as a template by inducing regeneration of the native tissue in which it was implanted (Cayan et al., 2002).
  • the biomembrane manufacturing process through chemical and thermal steps, allows to obtain a membrane with high tensile strength, allowing its placement in surgical sites with high demand for tensile strength and mechanical stress.
  • Morphological and birefringence analyzes of the biomembranes showed an extensive network of collagen fibers, organized in different directions, but preferably along the biomembrane axis. This is important information and it is in agreement with the results of the mechanical properties, where the biomembranes presented a great tensile strength (MPa) resistance.
  • MPa tensile strength
  • Biomembrane processing also allows the presence of 2 glycosaminoglycans (dermatan sulfate and, especially, heparan sulfate), which may aid in intrinsic bioactivity. This fact reflects a good adherence, migration, differentiation and response of cell culture.
  • the present invention can be used in the treatment of skin lesions such as diabetic or vascular burns and ulcerations, acts as a barrier against microorganisms and water loss and contributes to the wound healing process. And also used in reconstruction of soft tissues in urogynecological procedures, acting as a support for cell growth during the tissue remodeling process.
  • These biomembranes can still be prepared to adsorb drugs such as silver sulfadizine, which is used to treat skin lesions in burns. They may also incorporate growth and differentiation factors, such as rhBMP, enabling their release into the surgical site.
  • the collagenous membrane procurement process has a relatively low procurement cost, which makes it possible to have a lower market value than other similar materials manufactured in the international market, making it more accessible to patients requiring dental treatment in which it is produced. be used.
  • the biomembrane obtained therefore, is manufactured by a unique technological process that preserves the collagenic structure of the original tissue and prior to use, there is gamma radiation sterilization.
  • the present invention describes a process for obtaining a collagen membrane obtained from intestinal submucosa of porcine origin.
  • This process permits the obtaining of a biocompatible collagen membrane of natural origin, through chemical and thermal processes, and there is no permanence of chemical residues from reagents used in the obtaining process.
  • the permanence of these residues can lead to exacerbated inflammatory response and impairment of the tissue regeneration process.
  • the costs involved in raw material procurement and membrane processing allow the product to be marketed for a lower value than other membranes on the market.
  • an object of the present invention is a process for obtaining a collagen membrane comprising the steps of: (a) cleaning of the raw material, where cleaning is chosen from the group comprising:
  • the obtaining process has a preliminary step of preserving the raw material comprising immersion in salt water followed by washing with hypochlorite. In a preferred embodiment, the obtaining process has an additional finishing step involving membrane cutting and sterilization.
  • the treated material may be lyophilized, and lyophilization, if present, occurs after step c) and before finishing, and is preceded by a stretching step similar to step b).
  • a further object of the present invention is a biomembrane obtained by the process described above.
  • Figure 1 (a) - Schematic view of the "tubule” porcine intestinal submucosa - no cuts made longitudinally
  • Figure 1 (b) Schematic view of porcine intestinal submucosa cut longitudinally
  • Figure 1 (c) - Schematic view of open porcine intestinal submucosa (after longitudinal cut)
  • the proposed processing to obtain a collagen membrane can be performed from tissues of natural origin, preferably from animals, especially cattle and swine, and the intestine of these animals can be used.
  • tissues of natural origin preferably from animals, especially cattle and swine, and the intestine of these animals can be used.
  • collagen-rich tissues other than the intestine may be used and are within the scope of the present invention.
  • the tissue used should be collagen-rich, where collagen is selected from the group comprising collagen type I, II, III, IV and combinations thereof.
  • the process of obtaining the collagen membrane is a process comprising the steps of: a) cleaning the raw material, where cleaning is chosen from the group comprising:
  • the process may comprise a preliminary step of preserving the raw material.
  • the raw material is normally preserved salty until the moment of biomembrane preparation, using the proposed manufacturing method.
  • the raw material is then treated with sodium hypochlorite solution, preferably at a concentration of 0.01% for 30 minutes to eliminate possible contaminants. After this, the material is washed thoroughly with deionized water.
  • the material is then subjected to cleaning steps comprising mechanical and / or protease and / or lipase cleaning. These procedures are intended to clean the material, remove fats and proteins other than collagen.
  • the material should be washed again with deionized water until these chemical residues are removed.
  • the material should be treated with detergent solution (0.1% to 0.5% v / v, preferably 0.3%) with lipase, (0.01%) to 0.05%, preferably 0, 02%) and rinse again with plenty of deionized water.
  • the detergent used may be any detergent known in the art.
  • the material should be stretched over regular surfaces and subjected to temperatures from 5 o C to 65 ° C, and this stretching step occurs in several substeps.
  • the first sub step takes place at temperatures of 5 ° C to 10 ° C, preferably at 7 ° C for 8h to 16h, preferably 12h.
  • the regular surfaces to be used must not allow the release of residues and must not allow the stretched biomembranes to be firmly adhered to them so that they cannot be detached from them.
  • the membranes stretched in the smooth surface must be subjected again to a temperature 30 ° C to 40 ° C, preferably at 37 0 C for 18h 30h to preferably 24h.
  • the membranes should be kept stretched at 55 ° C to 65 ° C, preferably 60 ° C, for 8h to 16h, preferably 12h.
  • the membranes are then treated with 1N hydrochloric acid for 8 to 24 hours, preferably 16 hours.
  • Biomembranes should be rinsed again with deionized water until acidic solution is removed.
  • the material must again be stretched over regular surfaces and subjected to temperature of 5 ° C to 10 ° C, preferably 7 ° C for 8h to 16h, preferably 12h.
  • the membranes stretched at regular surface must be subjected again to the temperature of 30 ° C to 40 ° C , preferably 37 0 C for 18h to 30h, preferably 24h. After these steps, the membranes should be stretched at 55 ° C to 65 ° C, preferably 60 ° C, for 8h to 16h, preferably 12h.
  • the lyophilization process is followed, in which first the biomembranes must be stretched again on a regular surface and frozen (-90 ° C to -55 ° C). ), preferably -80 ° C for 8 to 24h, preferably 12h.
  • the lyophilized or non-lyophilized membranes are then cut according to an established parameter (eg 2cm X 2cm), packaged and subjected to gamma radiation for sterilization.
  • an established parameter eg 2cm X 2cm
  • the obtained membranes can be subjected to drug incorporation and / or growth and differentiation factors.
  • Non-lyophilized membrane preparation used as a dressing for treating burns
  • the raw material should be washed in 0.1% sodium hypochlorite solution for 0.5h. After this period, the coarser greasy tissue that can be removed mechanically should be removed. The membranes are washed thoroughly in deionized water.
  • the porcine intestinal submucosa is cut longitudinally in order to open the tubular structure, characteristic of this type of structure ( Figure 1).
  • the membranes are then placed in 0.002% lipase and 0.3% detergent enzyme solution for 2.5h. After this time, they are washed extensively with deionized water. They are then placed in 600 mL of another enzyme solution with 0.002% protease and 0.3% detergent. They are then again washed with extensively deionized water.
  • the detergent has the function of transforming the fat into smaller particles and thus facilitating the action of lipase.
  • Lipase is an enzyme whose function is to catalyze the hydrolysis of fats. This facilitates the removal of fats present in the raw material.
  • the membranes are removed from the Teflon surface and subjected to treatment in 1 N hydrochloric acid solution for 8h. They are then washed in deionized water for a period of 2h. Afterwards, the membranes are stretched again on a flat surface. They are then placed under refrigeration at a temperature of 7 ° C. The membranes undergo another heat treatment step at 37 ° C for 24h. They are subsequently submitted to a temperature of 60 ° C for 12h.
  • the raw material should be washed in 600 mL of solution with 0.1% sodium hypochlorite for 0.5h. After this period, the coarser greasy tissue that can be removed mechanically should be removed. Wash the membranes with abundant deionized water.
  • the membranes are then placed in enzyme solution with 0.02% lipase and 0.3% detergent for 2.5h. After this time, they are washed extensively with deionized water. They are then placed in another enzyme solution with 0.03% protease and 0.4% detergent. They are then again washed with extensively deionized water.
  • the proteases used are not specific for collagen proteins and therefore do not alter or denature them.
  • the membranes are removed from the stainless steel surface and treated with a solution of 0.1N hydrochloric acid for 24h. They are then washed in deionized water for 4 hours.
  • the biomombles are then cut to desired pattern and gamma-sterilized.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Botany (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Urology & Nephrology (AREA)
  • Biophysics (AREA)
  • Materials For Medical Uses (AREA)

Abstract

La présente invention concerne un procédé d'obtention d'une membrane de collagène à application médico-odontologique. Cette membrane, obtenue au moyen d'un procédé industriel comprenant des étapes de traitement chimique et thermique, permet de préserver les fibres de collagène, dont la disposition augmente la résistance à la traction et facilite l'enlèvement de cellules et de graisses du tissu d'origine.
PCT/BR2010/000221 2009-07-01 2010-06-29 Procédé de fabrication de membrane de collagène biocompatible à application médico-odontologique et produit ainsi obtenu WO2011000071A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
BRPI0902410A BRPI0902410B8 (pt) 2009-07-01 2009-07-01 processo de fabricação de membrana colagênica biocompatível para aplicação médico-odontológica e produto obtido
BRPI0902410-7 2009-07-01

Publications (1)

Publication Number Publication Date
WO2011000071A1 true WO2011000071A1 (fr) 2011-01-06

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5028695A (en) * 1988-03-11 1991-07-02 Chemokol Gesellschaft Zur Entwicklung Von Kollagenprodukten Process for the manufacture of collagen membranes used for hemostasis, the dressing of wounds and for implants
US6358284B1 (en) * 1996-12-10 2002-03-19 Med Institute, Inc. Tubular grafts from purified submucosa
US20040078076A1 (en) * 1996-08-23 2004-04-22 Badylak Stephen F. Purified submucosa graft material
WO2008067085A2 (fr) * 2006-10-23 2008-06-05 Cook Biotech Incorporated Materiaux de matrice extracellulaire traites presentant des profils de composants ameliores

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5028695A (en) * 1988-03-11 1991-07-02 Chemokol Gesellschaft Zur Entwicklung Von Kollagenprodukten Process for the manufacture of collagen membranes used for hemostasis, the dressing of wounds and for implants
US20040078076A1 (en) * 1996-08-23 2004-04-22 Badylak Stephen F. Purified submucosa graft material
US6358284B1 (en) * 1996-12-10 2002-03-19 Med Institute, Inc. Tubular grafts from purified submucosa
WO2008067085A2 (fr) * 2006-10-23 2008-06-05 Cook Biotech Incorporated Materiaux de matrice extracellulaire traites presentant des profils de composants ameliores

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DERWIN, K.A. ET AL.: "Commercial extracellular matrix scaffolds for rotator cuff tendon repair. Biomechanical, biochemical, and cellular properties.", JOURNAL OF BONE AND JOINT SURGERY AMERICAN VOLUME, vol. 88, no. 12, December 2006 (2006-12-01), pages 2665 - 2672 *
GILBERT, T.W. ET AL.: "Fiber kinematics of small intestinal submucosa under biaxial and uniaxial stretch.", JOURNAL OF BIOMECHANICAL ENGINEERING, vol. 128, no. 6, December 2006 (2006-12-01), pages 890 - 898 *

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BRPI0902410B8 (pt) 2021-07-27
BRPI0902410A2 (pt) 2011-03-09
BRPI0902410B1 (pt) 2020-03-03

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