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
  • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
  • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
  • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
  • A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
  • A61L15/325—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
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0061—Use of materials characterised by their function or physical properties
  • A61L26/009—Materials resorbable by the body
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
  • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
  • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
  • A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
  • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
  • A61L15/42—Use of materials characterised by their function or physical properties
  • A61L15/425—Porous materials, e.g. foams or sponges
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
  • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
  • A61L15/42—Use of materials characterised by their function or physical properties
  • A61L15/64—Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
• • 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
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
  • A61L26/0019—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• • 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
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
  • A61L26/0028—Polypeptides; Proteins; Degradation products thereof
  • A61L26/0033—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
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
  • A61L26/0052—Mixtures of macromolecular compounds
• • 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
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0061—Use of materials characterised by their function or physical properties
  • A61L26/0085—Porous materials, e.g. foams or sponges
• • 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
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0095—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
  • C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
  • C08L67/04—Polyesters derived from hydroxycarboxylic acids, e.g. lactones

Definitions

• the present invention relates to an absorbable cover membrane for medical treatment of wound surfaces.
• cover membrane is known, for example, from EP 1 181 941 A2 and is marketed by Polymedics GmbH, Germany, under the name Suprathel®.
• the cover membrane is used in medical practice as a wound contact material, e.g. B. as a skin replacement material for burns or for the treatment of so-called decollements, d. H. of scouring wounds of the skin.
• US Pat. No. 8,951,598 B2 discloses a cover membrane which has a biodegradable polymer carrier layer made from polylactic acid or polyglycolic acid has, which is doped with collagen nanoparticles.
• the polymer carrier layer can have, for example, a polylactide-glycolide copolymer (PLGA) with 10 to 40% by weight of nanoscale collagen particles.
• PLGA polylactide-glycolide copolymer
• cover membrane mentioned at the outset offers pain-relieving and anti-infective effects in open wound surface treatment and allows largely undisturbed formation of granulation tissue with good mechanical properties at the same time.
• the haemostatic effect of the cover membranes is quite limited and the cover membrane shows only a slow ability to adsorb and absorb liquids on bloody wound surfaces or those wetted with exudate.
• the cover membrane has collagen particles with a particle size of more than 80 ⁇ m, which are arranged and kept embedded at least in sections in the polymer material of the carrier layer. Due to the known swelling capacity of fibrillar collagen, ie collagen whose secondary or tertiary structure is intact, the binding of water to the cover membrane can be accelerated and the water-binding capacity of the cover membrane per unit area can be increased. In the present application, fibrillar or structurally intact collagen is understood to mean collagen whose ⁇ and ⁇ bands can be detected in the SDS-PAGE test.
• the collagen particles are anchored in the polymer material of the carrier layer, which is itself water-absorbent, the absorption of water by the polymer material of the carrier layer itself can also be promoted.
• the cover membrane When the cover membrane is applied to the wound surface, excess blood plasma and/or wound exudate can be removed from the wound surface more quickly and effectively.
• the swelling of the collagen particles increases the thickness of the cover membrane—at least locally—so that the distance between the cover membrane and the wound tissue supplied with it can increase, at least locally.
• the haemostatic properties of the cover membrane can be improved, and vascularization of the wound surface and thus wound healing can be accelerated.
• an appropriately flexible, deformable design of the cover membrane it can be easily adapted even to intraperitoneal surfaces that are difficult to cover three-dimensionally and to wound surfaces of the skin, for example in the area of joints.
• the collagen particles preferably have a particle size in the range from 80 ⁇ m to 500 ⁇ m, particularly preferably in the range from 100 ⁇ m to 250 ⁇ m, very particularly preferably in the range from 100 ⁇ m to 150 ⁇ m.
• the haemostatic effect of the collagen in situ decreases beyond an average particle size of approximately 500 ⁇ m and the anchoring of the collagen in the carrier layer is no longer sufficiently stable with respect to the mechanical forces acting on the cover membrane during handling and application is. This can lead to an undesired shearing of the collagen particles from the carrier layer.
• Particularly reliable hemostasis can be achieved with a particle size between 100 ⁇ m and 150 ⁇ m.
• the cover membrane has 0.4 to 80% by weight, preferably 0.5 to 25% by weight, of collagen particles. It should be noted that the improved haemostatic properties of the sheet material mediated by the collagen are already achieved with approximately 1% by weight of collagen. In this respect, the flat material can have in particular 0.4-2% by weight of collagen particles.
• the collagen particles extend away from the carrier layer.
• the collagen particles thus form a collagen pole on the back and front of the carrier layer. Due to the size of the collagen particles alone, the cover membrane in the area of the collagen pole is more hydrophilic than without such a collagen pole. With this structure of the cover membrane, an immediate bioavailability of the collagen particles and thus an even faster onset of hemostatic effect of the cover membrane can be achieved.
• at least a portion of the collagen particles can bulge over the front or rear surface area of the carrier layer that encompasses or surrounds the respective collagen particle.
• the respective collagen particle is preferably kept completely embedded in the polymer material of the carrier layer.
• the aforementioned collagen pole of the carrier layer has a structural height of more than 10%, preferably more than 20%, of the nominal thickness of the carrier layer.
• the carrier layer can have a collagen pole made of collagen fibers on both sides.
• this eliminates the risk of the cover membrane being applied the wrong way round on the wound surface to be treated with it.
• the collagen poles of the two sides of the carrier layer can differ from one another in terms of their nominal thickness, the average density of their collagen fibers per unit area of the cover membrane and/or the size of their collagen particles.
• one and the same cover membrane can be used for different wound management requirements, thus further expanding its range of application.
• cover membrane sections are folded over, an undesired mutual adhesion of cover membrane sections can be counteracted.
• the collagen pole on one side of the covering membrane can, for example, comprise collagen particles with an average particle size of 100 to 150 ⁇ m and the pole on the other side of the covering membrane can contain collagen particles with an average particle size between 250 and 500 ⁇ m. This can do that Swelling behavior of the collagen particles of the respective edging or pile of the carrier layer can be adapted to the respective wound area to be treated.
• the collagen particles of the covering membrane can in particular be made from native type I and/or type III collagen, in particular bovine collagen. Such collagen is available on the market in sufficient quantities and in high purity.
• the carrier layer can in particular comprise a copolymer based on the monomers lactide, glycolide, trimethylencarbonate, s-caprolactone and/or 1,4-dioxan-2-one or polyhydroxybutyrate (PHB) or mixtures of these polymers.
• the cover membrane can develop an anti-infective and pain-reducing effect, with complete hydrolytic and enzymatic degradability being fully retained.
• the carrier layer can contain 20% by weight to 99.6% by weight of copolymer and/or polyhydroxybutyrate and 0.4% by weight to 80% by weight of collagen particles with a particle size >80 ⁇ m, preferably 0.8% by weight. to 25% by weight of the collagen particles.
• the carrier layer can in particular comprise a terpolymer of 65 to 87% by weight of lactide, 5 to 20% by weight of trimethylene carbonate and 5 to 20% by weight of E-caprolactone.
• the monomers lactide, trimethylene carbonate and s-caprolactone can be present in the terpolymer in particular in the range from 85/10/5 to 70/20/10% by weight.
• the carrier layer of the cover membrane preferably has a nominal thickness d of 50 to 3000 ⁇ m, preferably 80 to 500 ⁇ m or 800 to 2500 ⁇ m.
• the method according to the invention for producing the cover membrane explained above comprises the following steps: • comminuting provided and preferably dried native collagen to form collagen particles with an average particle size greater than 80 ⁇ m, preferably greater than 100 ⁇ m;
• the suspension/dispersion of the collagen particles in the polymer solution has to be carried out very carefully in order not to further damage the collagen particles directly or through shearing forces, in particular to further comminute them.
• Very finely divided collagen ⁇ 50 ⁇ m degrades very quickly to gelatine in the polymer solution, so that the fibrils of the collagen particles with their original helical shape are destroyed. It is therefore procedurally necessary to maintain the particle size greater than 80 ⁇ m to preserve the integrity and desired function of the collagen in vivo. It is therefore necessary to focus on a size and structure-preserving suspension/dispersion of the collagen particles. According to the invention, this is preferably achieved in that the collagen particles are dispersed or suspended in the polymer solution by stirring for a maximum of two minutes, preferably for a maximum of one minute.
• the collagen particles it is also possible to suspend/disperse the collagen particles by stirring in the pure solvent for a maximum of two minutes, preferably one minute, and then carefully stirring the collagen suspension with the polymer solution. Drying stabilizes the carrier layer of the cover membrane. Longitudinal segments of the collagen particles arranged outside the carrier layer can partially stand up during drying or when the cover membrane is detached from the planar carrier. If the flat support is in the form of a plate, in particular a glass plate, with a completely flat surface, the back of the dried cover membrane is correspondingly smooth, ie in particular without collagen particles extending away from the back of the support material. If the cover membrane is to have a collagen pole on both sides, a glass plate with micro-indentations or, alternatively, a carrier with a microporous coating can be used as the planar carrier.
• the collagen particles are scattered onto the carrier or onto the polymer solution/collagen suspension applied to the carrier, this can be done solely by gravity or also forced by means of a compressed gas/compressed air. In this way, the collagen particles can be anchored particularly reliably in the polymer solution or the collagen suspension.
• the native collagen is preferably dried before it is comminuted, or the comminuted collagen particles are dried before they are suspended in the solution.
• a particularly efficient comminution of the collagen and in the latter case a particularly efficient suspension of the collagen particles in the solution can be achieved.
• FIG. 1 shows a cover membrane with a carrier layer, in which collagen particles with a particle size of more than 80 ⁇ m are anchored, in a schematic sectional view;
• FIG. 3 shows the cover membrane according to FIG. 2 in a plan view showing a collagen particle which is completely embedded in the polymer material of the carrier layer and protrudes over the (planar) surface area of the carrier layer surrounding the collagen particle.
• FIG. 4 shows the cover membrane according to FIG. 2 after swelling in water at 37° Celsius for several hours
• FIG. 5 shows a block diagram of a method according to the invention for producing a cover membrane according to the invention.
• FIG. 6 shows an SDS-PAGE test for detecting an undesired degradation of collagen particles as a function of the mixing time when mixing the collagen particles with a polymer solution.
• the cover membrane 10 comprises a carrier layer 12 with a front side and a back side 12a, 12b.
• the carrier layer 12 is structurally formed here by a copolymer based on the monomers lactide, trimethylene carbonate, E-caprolactone and/or 1,4-dioxan-2-one, or polyhydroxybutyrate (PHB) or mixtures of these polymers.
• the carrier layer 12 is therefore biocompatible and hydrolytically and/or degradable by endogenous enzymes and completely resorbable.
• the carrier layer has a nominal thickness d which, depending on the mechanical application requirements placed on the cover membrane 10, can be from 50 to 3000 ⁇ m, preferably from 80 to 500 ⁇ m or from 1000 to 2500 ⁇ m.
• collagen particles 14 are embedded in the material of the carrier layer 12, at least in sections. In other words, the collagen particles 14 are anchored in the material of the carrier layer 12 .
• the collagen particles 14 can be kept embedded in the polymer material of the carrier layer and, according to FIG. 1, at least partially extend away from the carrier layer 12 or bulge over the front side, as explained below in connection with FIG. If the collagen particles 14 extend away from the carrier layer, they can together form a collagen pole 16 of the carrier layer 12 .
• the structural height h of the collagen pole 16 can be more than 10%, preferably more than 20%, of the nominal thickness d of the carrier layer 12.
• the collagen particles 14 all consist of comminuted native collagen, for example type I and/or type III collagen, and can in particular be of bovine, murine or porcine origin.
• the collagen particles 14 have a particle size I of more than 80 ⁇ m, preferably between 100 ⁇ m and 500 ⁇ m, particularly preferably between 100 ⁇ m and 250 ⁇ m.
• the cover membrane 10 Due to the collagen pole 16, the cover membrane 10 has two different useful sides 18, 20 in the exemplary embodiment shown in FIG. If the cover membrane 10 is applied with its pole-side useful side 18 to a wound surface (not shown), direct contact with the wound surface by the collagen particles 14 is made possible. This ensures a particularly high bioavailability of the collagen and its functional advantages in the treatment of wound surfaces are fully exploited at an early stage. These include, in particular, the known haemostatic properties of fibrillar collagen, its swelling capacity due to a pronounced absorption capacity of blood and wound exudate, and its favorable effects with regard to rapid vascularization of the wound surface and wound healing. In practice it has been shown that even small mass fractions of the collagen particles 14 promote the aforementioned effects.
• the cover membrane 10 can comprise between 0.5 to 80% by weight of collagen particles 14, preferably between 0.8 to 25% by weight of collagen particles 14.
• the cover membrane 10 can be folded and respective folding sections (not shown), e.g. B. with their mutually facing back 12b, are superimposed. Particularly in the case of adhesion prophylaxis, this offers the advantage of a particularly large liquid absorption capacity in relation to the surface unit 22 of the folded cover membrane 10 in contact with the wound surface.
• laparoscopic application of the cover membrane can be facilitated as a result.
• the cover membrane 10 can also have a collagen pole 16 made of collagen particles 14 on both sides. In practice, this can on the one hand counteract an inadvertent laterally inverted application of the covering membrane 10 and provide a usable collagen surface 20 on both sides. At the same time, when the cover membrane is applied to a wound, an annoying sticking of the cover membrane 10 to itself can be counteracted.
• the collagen poles 16 on the front and back sides 12a, 12b of the carrier layer 12 can differ from one another in terms of the average density of their collagen particles 14 per unit area 22 of the cover membrane 10 and/or the size of their collagen particles 14 or their structural height h . As a result, a cover membrane 10 with different collagen useful sides 18, 20 can be provided and the possible range of uses of the cover membrane 10 in treating wound surfaces can thus be expanded.
• FIG. 2 shows a side view of the cover membrane, in which the nominal thickness d of the carrier layer can be clearly seen.
• 3 shows the ready-to-use cover membrane 10 in the area of a collagen particle 14 in a microscopic plan view and with a height profile along the measuring section marked S.
• the collagen particle 14 bulges together with the polymer material (locally limited) over the surface area 24 of the front side 12a of the carrier layer 12 surrounding the collagen particle 14 .
• the surface area 24 of the carrier layer 12 is planar or essentially planar.
• cover membrane 10 shown in Fig. 3 is placed in water and then analyzed by measurement, there is increased swelling of the cover membrane 10 in the area of a collagen particle 14, i.e. locally limited, compared to collagen-free carrier layer sections of the cover membrane or the collagen particle 14 surrounded 4 shows a microscope image of the cover membrane 10 after a water bath at 37° C. for 22 hours.
• the nominal thickness d (cf. FIG. 1) of the cover membrane 10 is approximately 250 ⁇ m on average according to the height profile image, with the collagen particle 14 shown (cf. FIG. 1) being approximately 350 ⁇ m over the surface region 24 of the carrier layer 12 (cf. FIG. 1) that encompasses the collagen particle 14 collagen particle-free carrier layer section) protrudes.
• the combination of the collagen particles 14 and the synthetic resorbable polymer e.g. polylactide-caprolactone-trimethylene carbonate
• the resorbable polymer material of the carrier layer 12 is in direct contact with the wound (eg a burn wound) and can improve wound healing through the enzymatic release of lactic acid and develop a pain-relieving and anti-infective effect.
• the method 100 has the following method steps:
• a first step 102 provided and preferably dried native collagen 200 is comminuted to form collagen particles 14 with a particle size greater than 80 ⁇ m, preferably greater than 100 ⁇ m.
• the collagen particles 14 can be suspended in an organic solvent 202, for example dimethyl sulfoxide (DMSO), to form a collagen stock suspension 204.
• DMSO dimethyl sulfoxide
• the collagen particles 14 are stable or largely stable in pure DMSO, so that the collagen particles 14 suspended in DMSO do not degrade.
• a polymer solution 206 is produced from an absorbable polymer 208 and a suitable solvent 210.
• step 108 the collagen particles 14 or the collagen particles 14 contained in the collagen stock suspension 204 are suspended/dispersed in the polymer solution 206 so that a collagen suspension 212 is obtained.
• the size and functionality of the collagen particles 14 ie structural integrity with detectability of o and ß bands in the SDS-PAGE test
• the collagen particles 14 are not stable, for example in a solution 206 of a statistical terpolymer of D,L-lactide-trimethylene carbonate-caprolactone, and can degrade over time to form collagen particles 14 with a grain size of ⁇ 50 ⁇ m.
• a speedy processing of Collagen Suspension 212 displayed.
• FIG. 6 shows the result of an SDS-PAGE test (sodium dodecyl sulfate polyacrylamide gel electrophoresis test) of the collagen suspension 212 as a function of the stirring time using an aforementioned Ultra Turrax® stirrer.
• SDS-PAGE test sodium dodecyl sulfate polyacrylamide gel electrophoresis test
• a protein marker PM protein marker: "Precision Plus Protein Standard” from BioRad with defined molecular weights between 10 - 250 kDa; 10 ⁇ l sample volume
• the reference bands typical of the protein marker PM are shown
• a solution containing native bovine collagen sample volume 4 ⁇ l
• a sample (sample volume 33 ⁇ l) of the collagen suspension 212 was applied with a stirring time of 2 ⁇ 15 s (lane 7), 2 ⁇ 30 s (lane 8), 2 x 60 s (lane 9) and 2 x 5 min (lane 10).
• the collagen bands (o, ß and y regions) typical of collagen particles 14 can be clearly seen with an Ultra Turrax® mixing time of 2 ⁇ 15 s (lane 7). Even with a mixing time of 2 x 30 s and 2 x 60 s, the intensity of the bands in the y and ß region decreases increasingly. With a mixing time of 2 x 5 min, the bands in the y-region are almost no longer recognizable and the bands in the o- and ß-region are clearly less pronounced. Astonishingly, the reduction in the intensity of the o, ß and y regions shows a clear degradation of the collagen even after stirring for 5 minutes. With even longer stirring, the alpha and beta bands in the collagen suspension 212 can also no longer be recognized (not shown).
• the collagen particles 14 are preferably dispersed/suspended in the respective polymer solution 206 for less than 2 minutes, very particularly preferably for a maximum of 1 minute.
• the collagen suspension 212 obtained in this way is applied to a flat carrier 216 in step 110, preferably by means of a doctor blade 214.
• a glass plate can be used as the flat carrier 216 .
• the collagen suspension 212 is dried, in particular freeze-dried, and the solvent 210 is thereby removed.
• the collagen particles 14 in step 114 can also be applied to the flat carrier 210 before the solution 206 or the collagen stock suspension 212 is applied to the flat carrier 210 or after the application of the solution 206/collagen suspension 212 be applied or scattered onto the planar carrier 210 onto the solution 206/collagen suspension 212. In the latter case, this can be done by means of a compressed gas or by means of compressed air in order to introduce the collagen particles 14 into the solution 206 or the collagen suspension 212 at least in sections.
• step 102 0.5 g of dried bovine collagen 200 is comminuted into collagen particles 14 with a grain size>80 ⁇ m.
• the collagen particles 14 are subsequently dispersed in an organic solvent 202 in step 104 to obtain a collagen stock suspension 204 .
• the collagen particles 14 are added, for example, to 49.5 g of dimethyl sulfoxide (DMSO) and gently dispersed therein for 15 seconds. This gives a 1% collagen stock suspension 204.
• DMSO dimethyl sulfoxide
• a 150 g example of a 23% solution 206 of a statistical terpolymer of D,L-lactide-trimethylene carbonate-caprolactone in a solvent 208 is provided.
• step 108 a total of 50 g of 1% DMSO collagen stock suspension 204 is mixed with 150 g of 23% solution of a random terpolymer of D,L-lactide-trimethylene carbonate-caprolactone Mixed collagen suspension 212 and homogenized twice for 15 seconds each time by stirring.
• the collagen suspension 212 is squeegeed onto the carrier 216, for example a glass plate, using a squeegee 214 with a squeegee gap of 250 ⁇ m, and then in step 112 freeze-dried.
• the carrier 216 for example a glass plate
• a squeegee 214 with a squeegee gap of 250 ⁇ m
• step 112 freeze-dried.
• step 108 a total of 1.15 g of ground collagen particles 14 with a particle size >80 ⁇ m are added to 100 ml of a 23% polymer solution 206 of a statistical terpolymer of D,L-lactide trimethylene carbonate-caprolactone in DMSO and stirred gently to form the collagen suspension 212 .
• the collagen suspension 212 is then squeegeed onto the flat carrier 216 in step 110 using a squeegee 214 with a squeegee gap of 500 ⁇ m. Finally, the solvent 210 of the collagen suspension 212 is removed by freeze-drying the collagen suspension 212 . This creates an approximately 100-250 ⁇ m thick cover membrane in the form of a collagen composite membrane made from 95% of a random terpolymer of lactide-trimethylene carbonate-caprolactone and 5% collagen particles 14 with a grain size>80 ⁇ m.
• step 102 native cattle collagen is comminuted into collagen particles 14 with an average particle size of >80 ⁇ m. Then, in step 104, 0.25 g of the dried collagen particles 14 are added to 49.5 g DMSO and gently dispersed for 15 seconds. This gives a 1% collagen stock suspension 204.
• step 108 50 g of the 1% DMSO collagen stock suspension 204 are mixed with 150 g of a 12.5% solution of a random terpolymer of D,L-lactide-trimethylene carbonate-caprolactone and homogenized 2 ⁇ 15 seconds by stirring.
• the collagen suspension 212 obtained in this way is squeegeed onto the flat carrier 216 using a squeegee 214 with a squeegee gap of 600 ⁇ m.
• the collagen suspension 212 is freeze-dried, so that a cover membrane with a nominal thickness of approximately 180 ⁇ m d made of 98.6% lactide-trimethylene carbonate-caprolactone terpolymer and 1.4% bovine collagen particles 14 with a grain size>80 ⁇ m is obtained.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Materials Engineering (AREA)
• Public Health (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Veterinary Medicine (AREA)
• Hematology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Dispersion Chemistry (AREA)
• Composite Materials (AREA)
• Medicinal Chemistry (AREA)
• Polymers & Plastics (AREA)
• Organic Chemistry (AREA)
• Materials For Medical Uses (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=79170951

Family Applications (1)

Country Status (8)

Family Cites Families (8)

• 2020
  • 2020-12-03 DE DE102020215295.0A patent/DE102020215295A1/de not_active Ceased
• 2021
  • 2021-12-03 PE PE2023001776A patent/PE20240364A1/es unknown
  • 2021-12-03 MX MX2023006608A patent/MX2023006608A/es unknown
  • 2021-12-03 KR KR1020237021768A patent/KR20230116852A/ko active Search and Examination
  • 2021-12-03 JP JP2023533886A patent/JP2023551572A/ja active Pending
  • 2021-12-03 WO PCT/EP2021/084215 patent/WO2022117840A2/de active Application Filing
  • 2021-12-03 EP EP21835198.9A patent/EP4232102A2/de active Pending
• 2023
  • 2023-06-01 US US18/327,838 patent/US20230390453A1/en active Pending

Also Published As

Similar Documents

Legal Events