WO2010137043A1 - Biomatériel hémostatique provenant de fractions de déchets de processus de fractionnement de plasma humain - Google Patents

Biomatériel hémostatique provenant de fractions de déchets de processus de fractionnement de plasma humain Download PDF

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Publication number
WO2010137043A1
WO2010137043A1 PCT/IT2009/000230 IT2009000230W WO2010137043A1 WO 2010137043 A1 WO2010137043 A1 WO 2010137043A1 IT 2009000230 W IT2009000230 W IT 2009000230W WO 2010137043 A1 WO2010137043 A1 WO 2010137043A1
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WIPO (PCT)
Prior art keywords
biomaterial
process according
fraction
solution
foam
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PCT/IT2009/000230
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English (en)
Inventor
Raniero D'ascoli
Leonardo Pajewski
Francesco Veglio'
Original Assignee
Baxter Manufacturing S.P.A.
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Application filed by Baxter Manufacturing S.P.A. filed Critical Baxter Manufacturing S.P.A.
Priority to PCT/IT2009/000230 priority Critical patent/WO2010137043A1/fr
Publication of WO2010137043A1 publication Critical patent/WO2010137043A1/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
    • A61L27/36—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
    • A61L27/3616—Blood, e.g. platelet-rich plasma
    • 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
    • A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
    • 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
    • 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
    • A61L27/38—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 containing added animal cells
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—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
    • 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 biocompatible biomaterial, in particular a biocompatible sponge, deriving from protein pastes obtained as by-products of human plasma fractionation, if necessary processed in a scaffold of other biomaterials such as collagen, hyaluronic acid, etc.
  • the invention further relates to a method for obtaining the biocompatible material and to the use thereof as a biocompatible material and as a support for cell cultures in tissue engineering applications.
  • protein pastes obtained from a variant of Conn's fractionation process e.g. FRACTION I, FRACTION III and FRACTION IV 1-4, are disposed of as industrial waste.
  • a way to reduce these costs consists in recycling protein fractions by turning them into useful products which can be marketed and thus become a source of profit (and not of costs) for the company.
  • the method of the invention disclosed in the present patent application, enables to produce a biomaterial that is useful for different aims and therefore marketable.
  • haemostatic biomaterials obtained from proteins of animal origin, in particular of bovine origin, such as Spongostan sponge (manufactured by Ferrosan) .
  • haemostatic pads based on regenerated cellulose or based on collagen see e.g. US 6,649,162, US 6,454,787, US 7,186,684. It is also known about biomaterials obtained from plasma components (see e.g. US 7,009,039, - A -
  • the haemostatic biomaterial of the present invention is therefore an advantageous alternative to haemostatic pads of animal origin and to other known or commercial sponges.
  • a haemostatic product deriving from human plasma proteins is advantageous in that it has a better interaction with body fluids favored by the porous structure and by its biocompatibility, it accelerates platelet activation (thus reducing blood coagulation times) and improves absorption and metabo- lization of the material itself.
  • manufacturing this product involves no costs for raw materials since it is obtained from the transformation of a waste protein paste.
  • the recycling of waste material which would normally be disposed of according to existing regulations, involves lower disposal costs and enables the company to turn a cost into a material to be sold.
  • FIG. 1 shows a block diagram of the plasma protein fractionation process known in the field
  • FIG. 2 shows a block diagram of the process for manufacturing the haemostatic material from plasma protein waste fractions according to the invention
  • FIG. 3 shows the typical mechanical behavior of the new material, which, submitted to a compression test, is deformable and soft and wholly recovers the high deformations it has undergone;
  • FIG. 4 shows the average load variation expressed in kPas, corresponding to a material deformation of 80%, after treatment with glutaraldehyde and gamma irradiation with a dose of 25 kGy;
  • FIG. 5 shows the modes of in-vitro biocompatibili- ty test by cultivating human fibroblasts on the new biomaterial immersed in the culture medium;
  • FIG. 6 shows the results of a comparison between the haemostatic properties of the material according to the invention, with respect to the haemostatic ma- terials most frequently used in surgery;
  • FIG. 7 shows growth curves for fibroblasts in cell cultures prepared for verifying the biocompatibility of the pads of material according to the invention; the biomaterial is biocompatible irrespective of the reticulation executed with glutaraldehyde;
  • FIG. 8 shows the colonization of the biomaterial surface by adhering fibroblasts; left: pad obtained with addition of polyethylene glycol, right: pad obtained with addition of polyethylene glycol and reticulated with glutaraldehyde;
  • FIG. 11 shows average haemorrhage duration in rats not treated with heparin as a function of different haemostatic materials used
  • FIG. 12 shows average haemorrhage duration in rats treated with heparin as a function of different haemostatic materials used
  • FIG. 13 shows haemostatic collagen pads modified by addition of waste fraction Fraction I; on the left a collagen felt; on the right a collagen felt fragment imbibed with Fraction I solution and dried; - Figure 14 shows sponges obtained from Fraction I with addition of collagen.
  • the present invention relates to a method for preparing a biomaterial from at least one protein fraction obtained as a by-product of human plasma fractionation process, in particular of modified Conn' s process, disclosed in detail below.
  • the biomaterial is obtained from waste fractions obtained as a protein by-product from modified * Cohn's process for processing plasma: FRACTION I, FRACTION III or FRACTION IV 1-4.
  • the most preferred protein fraction as a starting product for preparing the biomaterial of the invention is FRACTION I.
  • the biomaterial according to the invention is obtained from whole, untreated plasma .
  • the biomaterial of the invention is obtained by adding to a biomaterial scaffold, e.g. a collagen or hyaluronic acid scaffold, at least one waste fraction obtained from modified Conn' s human plasma fractionation process.
  • a biomaterial scaffold e.g. a collagen or hyaluronic acid scaffold
  • the waste fraction that are preferably used are FRACTION I, FRACTION III OR FRACTION IV 1-4.
  • FRACTION I is the most preferred.
  • the biomaterial obtained with the single steps covered by the present invention has shown haemostatic properties, i.e. it can reduce and/or stop blood flow from surface or internal injuries.
  • the biomaterial has proved particularly useful as a haemostatic material' for use in surgery when haemostatic pads that are effectively able to reduce, control and stop bleeding are needed.
  • the haemostatic biomaterial according to the present invention is preferably a haemostatic sponge.
  • the biomaterial according to the invention has also proved useful as a scaffold for cell cultures in tissue engineering applications.
  • Plasma obtained from blood by plasmapheresis or by separation from whole blood, is subjected to a fractionation treatment using modified Cohn' s process, which has already been used for a long time by the Applicant for protein separation.
  • Plasma stored at a temperature of ⁇ -20 0 C, is sent to the first blood serum processing line (Mass-Capture) where it is thawed.
  • the first process step involves the addition of ethyl alcohol up to a concentration of 5 to 10% (v/v) , pH adjustment around 7 by adding hydrochloric acid and soda, and an ageing of the suspension thus obtained for about 2 hours at a temperature of -1 to 1°C.
  • This step is followed by a centrifugation giving a cake (FRACTION I), which is an industrial waste, and a supernatant (SUPERNATANT I) which continues processing and undergoes another centrifugation, after adjusting alcohol concentration to values of 20 to 30% (v/v) .
  • This second centrifugation gives a cake (FRACTION II + III) , which undergoes in its turn further processing operations for obtaining immuno-globulins, in particular immuno-gamma globulin IgG, and a supernatant (SUPERNATANT II + III) .
  • the supernatant II + III by precipitation with alcohol and pH adjustment, gives a precipitate (FRACTION IV-I, 4) containing ⁇ -globulins and ⁇ -globulins, and a supernatant (SUPERNATANT IV-I, 4) subjected to a filtration operation with a press filter, enhanced by ce- lite addition.
  • This process step gives a cake (FRACTION IV-I, 4 + CE- LITE) and a filtrate.
  • the filtrate is subjected to a subsequent treatment for adjusting pH to values around 5.30-5.40, and sent to a further filtration, still with press filter, so as to obtain a supernatant (RAW SUPERNATANT V) , which is then subjected to distillation for recovering etha- nol, and a precipitate (RAW FRACTION V) from which albumin is extracted.
  • RAW FRACTION V is re-suspended in physiological solution, subjected to pH adjustment up to values of 4.4- 4.8 with hydrochloric acid and soda, adjusted to an alcohol concentration of 8 to 15% and then filtered. Filtration, together with the addition of celite, gives a cake, which is disposed of, and a filtrate, which is subjected to the same operations as the pre- vious one, suitably modifying experimental parameters. Filtration is executed in a press filter and allows to separate a supernatant, which is subjected to distillation for ethanol recovery, and a solid portion, rich in albumin, which is known as PURIFIED FRACTION V. This fraction is further treated for obtaining the end product (albumin) , first by clarification filtration and then by washing.
  • FRACTION I is more preferably used in the present invention as a starting product for preparing a bioma- terial, in particular a haemostatic sponge.
  • FRACTION I comprises 20 to 40% of proteins dispersed in an aqueous phase.
  • the proteins included in FRACTION I are albumin, ⁇ - globulins, ⁇ -globulins, ⁇ -globulins and fibrinogen.
  • the temperature of the process step in which FRACTION I is obtained is preferably of -1 to 1°C. After obtaining the material, the latter is kept at a temperature of -18 to -20 0 C.
  • Waste protein fractions from a plasma fractionation process in particular FRACTION I, FRACTION III or FRACTION IV 1-4 (preferably FRACTION I) of modified Conn' s fractionation process, are subjected to the recycling process of the present invention (disclosed below with reference to Figure 2) for obtaining a bio- material which is preferably a haemostatic sponge.
  • a waste protein fraction of paste preferably FRACTION I, including plasma proteins, water and alcohol, is mixed with a basic solution, preferably a sodium bicarbonate solution, so as to keep pH at a value of 7 to 9, preferably of 7.2 to 8.2.
  • the paste and the basic solution are mixed in a solid/liquid ratio of 1 to 4, preferably of 1 to 3.
  • the protein paste is then shredded to a small particle size (few millimeters) so as to simplify protein dissolution process with the solvent.
  • the protein paste can be homogenized before dissolution.
  • Dissolution is obtained by stirring the system proteins/solvent for a time of 1 to 4 hours, preferably of 1.5 to 3 hours (time necessary for complete re- suspension of protein paste) .
  • Polyethylene glycol can coordinate water molecule so as to reduce evaporation during the drying step, and it is added in an amount of 20 to 60%, preferably of 30 to 50%, of the protein content of the colloidal so- lution .
  • Polyethylene glycol interacts with water molecules and gives the solid structure a higher deformability without breaks, as shown in Figure 3.
  • At least one biomateri- al e.g. collagen and/or hyaluronic acid, is further added.
  • said at least one bioma- terial is used as a gel or powder.
  • collagen or hyaluronic acid in powder form obtained by grinding collagen or hyaluronic acid felts is used.
  • the biomaterial powder preferably collagen and/or hyaluronic acid
  • physiological solution up to balance with water.
  • the biomaterial gel particles thus obtained are added to the solution of fraction I, preferably in an amount of 20 to 70% m/m.
  • polyethylene glycol and/or a biomaterial preferably collagen and/or hyaluronic acid
  • the temperature of the solution is of 20 to 30 0 C, preferably 25°C.
  • the foam thus obtained can be added with a solution of a reticulating agent which is able to bind two amine groups of the protein, acting as intermolecular cross- linker.
  • the addition of a reticulation agent enhances the mechanical properties of the material.
  • the reticulating agent is preferably added while the foam is still under stirring, short before the drying step. Thus, foam is homogenized.
  • the reticulating agent used is an aldehyde, preferably • glutaraldehyde .
  • the amount of reticulating agent to be added to the foam is of 5 to -40% v/v, preferably 10 to 20% v/v.
  • the reticulating agent is advantageously used in aqueous solutions at concentrations of 0.00001 to 0.00005% of reticulating agent.
  • the addition of this compound should be executed short before the drying step so as to avoid premature formation of intermolecular links.
  • the drying step occurs at a temperature of 60 to 98 0 C, preferably of 70 to 95°C, for a time ranging from 10 to 40 hours, preferably from 15 to 25 hours. It is thus possible to remove both the alcohol, which volatilizes at lower temperatures, and water, which requires higher temperatures and times to be completely eliminated.
  • a pre-heating (or stabilization) step is carried out, preferably in a microwave oven.
  • Irradiation with microwaves has two effects: it flattens temperature profile inside the foam; it causes a rapid thermal denaturation of proteins, turning the liquid foam into a meta-stable gelatinous foam.
  • Pre-heating is executed for the time required to rapidly reach a temperature of about 80 0 C inside the foam to be dried.
  • the end product i.e. the biomaterial which in the preferred case is a haemostatic sponge.
  • the biomaterial thus obtained is advantageously packaged with a hermetic polymeric package (preferably made of polyethylene) and subjected to sterilization with radiation.
  • the biomaterial is advantageously irradiated with a dose of gamma or beta sterilizing radiations in the range from 10 to 40 kGy, preferably from 20 to 30 kGy.
  • This treatment ensures the reduction of. bacterial charge and of most viruses, which are also very sensitive to the thermal treatment in an oven, which the biomaterial is subjected to even before the treatment with radiations.
  • An alternative embodiment makes use of a scaffold of at least one biomaterial, preferably collagen and/or hyaluronic acid, which is added with at least one waste fraction from a human plasma fractionation process, in particular from modified Conn' s process.
  • a solid scaffold of at least one biomaterial imbibed with at least one waste fraction from a human plasma fractionation process is obtained.
  • the fraction which is preferably used is FRACTION I, FRACTION III or FRACTION IV 1-4, preferably FRACTION I.
  • the scaffold thus imbibed can be further added with polyethylene glycol.
  • the scaffold thus treated is dried (as described above) so as to obtain a biomaterial comprising hyaluronic acid and/or collagen and a protein waste fraction of the human plasma fractionation prpcess.
  • the drying step can follow a pre-heating step and be executed 'before packaging and irradiation, as described above.
  • the biomaterial obtained from the process of the in- vention can stop bleeding caused by injuries, i.e. it has haemostatic properties.
  • the biomaterial according to the invention has also proved useful as a scaffold for cell cultures in tissue engineering applications.
  • a preferred object of the present invention is therefore a haemostatic biomaterial, in particular a haemostatic sponge, obtained from FRACTION I, from other waste fractions of the human plasma fractionation process or from whole, untreated plasma, if necessary mixed with a biomaterial, preferably collagen and/or hyaluronic acid.
  • Example 1 Raw material to be used (see Figure 1) . All waste fractions from plasma fractionation process can be used, including whole, untreated plasma. Some of these require a few preliminary operations such as microfiltration in order to remove solid celite particles from Fraction 4. The best results were achieved using Fraction 1 and the following descriptions refer to such raw material.
  • Example 2 Dissolution of proteins constituting Fraction 1 (see Figure 2) .
  • PEG polyethylene glycol
  • Example 3 Homogenization of the system proteins/solvent (see Figure 2) .
  • Example 5 Addition of glutaraldehyde (see Figure 2) .
  • This reticulating agent can be added to dissolved pro- of the finished foam. While testing the mechanical properties of the finished pads with the compression test, pads both made of weakly reticulated proteins and not were examined. Also biocompatibility tests with in-vitro cell cultures were carried out both on reticulated and non-reticulated pads.
  • the glutaralde- hyde solution was added to the foam at the end of the formation thereof (after 7 minutes stirring) in an amount of 10% v/v of the initial protein solution volume. The concentration of the aqueous glutaraldehyde solution added is of 0.000025% v/v.
  • Example 7 Microwave pre-heating (see Figure 2) .
  • the foam contained in the moulds was rapidly pre-heated.
  • Preheating was carried out using microwaves with a double goal: flattening the temperature profile within the foam and causing a rapid thermal denaturation of proteins, turning the liquid foam into a meta-stable gelatinous foam.
  • Microwave pre-heating was carried out until a temperature of 80 0 C was reached at the center of the foam mass.
  • Example 8 Oven drying (see Figure 2) .
  • Example 9 Fad packaging (see Figure 2) . Pads were cut from the masse of dried foam and then placed into hermetic polyethylene bags, closed by heat sealing .
  • Example 10 Final sterilization (see Figure 2).
  • the pads closed inside the heat-sealed blisters were subjected to sterilization of a dose of 2'5 kGy of gamma radiation.
  • factor B The effect of radiation, referred to as factor B, was investigated on two levels (the first level without sterilization, referred to as - ⁇ , and the second level with a dose 25 kGy of applied gamma radiation, referred to as + ⁇ ) .
  • Tests were carried out twice using dynamometer ZWICK BZ2.5/TN1S at a deformation speed of 4 mm/minute. Compression tests were performed until a relative deformation of 80% was achieved.
  • Figure 4 shows the average development of load corresponding to a deformation of 80% as a function of the treatment with glutaraldehyde and with radiation.
  • cell cultures of human fibroblasts were carried out in presence of fragments of pads treated with glutaraldehyde (tests referred to as +GA) und not treated with glutaraldehyde (referred to as -GA) .
  • the pads used for the tests were sterilized with a dose of 25 kGy of gamma radiation.
  • the cell line used for experimentation consists of human fibroblasts (intestinal submucosa) proliferating spontaneously in presence
  • Figure 7 summarizes the results of these counts as growth curves which show the biocompatibility of the pads obtained both without reticulation with glutaral- dehyde and with materials reticulated with the latter. After 21 days from the inoculation, cells adhering to the pad surface were found, which demonstrates not only the biocompatibility of the material, but also that this can be used as scaffold for tissue engineering applications .
  • Example 13 In-vivo control of haemostatic properties of the new biomaterial (see Figure 9) .
  • haemostatic pads were compared with each other: the new pad obtained from waste fractions of human plasma fractionation, and common haemostatic devices used in surgery: cotton gauze, regenerated cellulose gauze and bovine gelatin sponge.
  • Tests were performed on male adult Wistar rats weighing 250-300 g, supplied by Harlan-Nossan, measuring the time from injury incision to haemorrhage stop. Before starting the tests, all the animals were anesthetized with 2 ml i.p. of Hydrate Chloralium (3.6 g/100 ml in physiological solution) .
  • Tests were carried out on groups of 4 animals on which the pad of cotton gauze was applied on the left and the haemostatic pad (the new pad, the regenerated cellulose gauze and the bovine gelatin sponge) on the right, both applied on the injury of small vein, medium vein and liver incision, for a total of 6 tests on each animal as schematically shown in Figure 10.
  • the results of these measures (72 in total) were subjected to an analysis of variance, which showed that the level of significance of the influence of the main factor "haemostatic material" is p>95%.
  • a second group of rats was pre-treated with a heparin dose (2000 IU/kg) .
  • heparin tests the gauze was not taken into account, since it is not suitable for stopping bleeding injuries in such extreme conditions.
  • the test pattern is shown in Figure 10, where the new bio- material was applied on the left side of the animal in the same place as the cotton gauze, whereas on the right size commercial haemostatic pads were applied (regenerated cellulose gauze and bovine gelatin sponge) , still . in groups of 4 animals for a total of 48 assays. Also these measures were subjected to an analysis of variance, which showed that the level of significance of the influence of the main factor "haemostatic material" is p>95%.
  • Example 14 Modification of a haemostatic pad comprising collagen by addition of waste proteins from human plasma processing (see Figure 13) .
  • Example 15 Haemostatic pad obtained from powder collagen added to waste proteins from human plasma processing (see Figure 14) .
  • a collagen in powder form was used, obtained by grinding felts as referred to in example 14.
  • the powders were covered with physiological solution (0,9% NaCl in H 2 O) and balanced with water. Then, after removing the supernatant, the collagen gel particles were added to the solution of fraction 1 obtained as described in examples 2 and 3, in an amount of 50% m/m.
  • the collagen particle suspension was subjected to processing as described in examples 4, 5, 6, 7, 8, 9 and 10.

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Abstract

La présente invention porte sur un biomatériel, biocompatible, en particulier, sur une éponge biocompatible issue de pâtes protéiques obtenues en tant que sous-produits de fractionnement de plasma humain et facultativement traités dans un échafaudage d'autres biomatériels tels que le collagène, l'acide hyaluronique, etc. La technologie de l'invention permet de recycler une ou plusieurs fractions protéiques obtenues en tant que sous-produits et qui sont habituellement jetés en tant que déchet industriel, augmentant ainsi les coûts de fabrication. Le procédé décrit permet d'obtenir un biomatériel possédant des propriétés hémostatiques. D'autres utilisations possibles portent sur son utilisation en tant qu'échafaudage pour des cultures cellulaires dans des applications d'ingénierie tissulaire.
PCT/IT2009/000230 2009-05-27 2009-05-27 Biomatériel hémostatique provenant de fractions de déchets de processus de fractionnement de plasma humain WO2010137043A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2492458A (en) * 1944-12-08 1949-12-27 Jr Edgar A Bering Fibrin foam
WO2001062312A1 (fr) * 2000-02-25 2001-08-30 Monterey Biomedical, Inc. Pansement a formation de mousse
US6548729B1 (en) * 1997-09-19 2003-04-15 Baxter Aktiengesellschaft Fibrin sponge
US7009039B2 (en) * 2001-07-19 2006-03-07 Prochon Biotech Ltd. Plasma protein matrices and methods for their preparation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2492458A (en) * 1944-12-08 1949-12-27 Jr Edgar A Bering Fibrin foam
US6548729B1 (en) * 1997-09-19 2003-04-15 Baxter Aktiengesellschaft Fibrin sponge
WO2001062312A1 (fr) * 2000-02-25 2001-08-30 Monterey Biomedical, Inc. Pansement a formation de mousse
US7009039B2 (en) * 2001-07-19 2006-03-07 Prochon Biotech Ltd. Plasma protein matrices and methods for their preparation

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