Classifications

• • D—TEXTILES; PAPER
  • D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
  • D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
  • D06M11/00—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising
  • D06M11/07—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising with halogens; with halogen acids or salts thereof; with oxides or oxyacids of halogens or salts thereof
  • D06M11/30—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising with halogens; with halogen acids or salts thereof; with oxides or oxyacids of halogens or salts thereof with oxides of halogens, oxyacids of halogens or their salts, e.g. with perchlorates
• • 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
  • A61L15/28—Polysaccharides or their derivatives
• • 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
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
  • C08B15/00—Preparation of other cellulose derivatives or modified cellulose, e.g. complexes
  • C08B15/02—Oxycellulose; Hydrocellulose; Cellulosehydrate, e.g. microcrystalline cellulose
  • C08B15/04—Carboxycellulose, e.g. prepared by oxidation with nitrogen dioxide
• • D—TEXTILES; PAPER
  • D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
  • D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
  • D06M11/00—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising
  • D06M11/58—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising with nitrogen or compounds thereof, e.g. with nitrides
  • D06M11/64—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising with nitrogen or compounds thereof, e.g. with nitrides with nitrogen oxides; with oxyacids of nitrogen or their salts
• • D—TEXTILES; PAPER
  • D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
  • D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
  • D06M13/00—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with non-macromolecular organic compounds; Such treatment combined with mechanical treatment
  • D06M13/322—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with non-macromolecular organic compounds; Such treatment combined with mechanical treatment with compounds containing nitrogen
  • D06M13/35—Heterocyclic compounds
  • D06M13/355—Heterocyclic compounds having six-membered heterocyclic rings
• • D—TEXTILES; PAPER
  • D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
  • D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
  • D06M13/00—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with non-macromolecular organic compounds; Such treatment combined with mechanical treatment
  • D06M13/322—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with non-macromolecular organic compounds; Such treatment combined with mechanical treatment with compounds containing nitrogen
  • D06M13/388—Amine oxides
• • D—TEXTILES; PAPER
  • D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
  • D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
  • D06M2101/00—Chemical constitution of the fibres, threads, yarns, fabrics or fibrous goods made from such materials, to be treated
  • D06M2101/02—Natural fibres, other than mineral fibres
  • D06M2101/04—Vegetal fibres
  • D06M2101/06—Vegetal fibres cellulosic
• • D—TEXTILES; PAPER
  • D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
  • D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
  • D10B2201/00—Cellulose-based fibres, e.g. vegetable fibres
  • D10B2201/20—Cellulose-derived artificial fibres
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
  • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
  • Y02P20/00—Technologies relating to chemical industry
  • Y02P20/50—Improvements relating to the production of bulk chemicals
  • Y02P20/582—Recycling of unreacted starting or intermediate materials
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T428/00—Stock material or miscellaneous articles
  • Y10T428/249921—Web or sheet containing structurally defined element or component

Definitions

• the present invention provides a novel solid material based on polymer containing at least partially oxidized cellobiose units, capable of being used in the medical field, particularly as a compress.
• Such a material advantageously a textile, may be obtained by submitting a solid material based on a polymer containing cellobiose units to a method in at least two steps: placing it in contact with an oxidizing mixture comprising a hypohalite, a halite, and an oxo-ammonium salt or a precursor of said salt; placing in contact the material thus processed with a solution of periodic acid or of a salt thereof; and then, possibly, placing in contact the material thus processed with a halite.
• Surgical haemostatic compresses, or compresses should be haemostatic, absorbable, and easy to manipulate by surgeons. Such properties may be obtained due to textiles based on oxidized cellulose.
• cellulose is a homopolymer belonging to the class of polysaccharides. It is formed of a linear chain of glucose molecules or anhydroglucose units (D-anhydroglucopyranose), interconnected by glycosidic bonds ⁇ -1,4. Cellulose may also be defined as a chain of cellobiose units:
• Document WO 2009/016325 describes an alternative method of oxidizing cellulose within a fabric, by means of an oxidizing catalytic system comprising 1-oxo-2,2,6,6-tetramethylpiperidine-1-oxide (TEMPO), NaBr, and NaClO. This reaction occurs at low temperature and at a basic pH which has to be strictly controlled during the reaction.
• TEMPO 1-oxo-2,2,6,6-tetramethylpiperidine-1-oxide
• NaBr NaBr
• NaClO NaClO
• Singh et al. have described a cellulose oxidation method, based on the use of sodium periodate.
• the cellulose thus processed which exhibits aldehyde functions and a ring opening, has a slow in vivo absorption.
• the aldehyde functions may be used to immobilize, in particular, enzymes of interest.
• the present invention provides a novel solid material based on oxidized cellulose, usable as a compress and capable of being obtained due to an original process.
• the present invention provides a solid material based on a polymer containing cellobiose units, wherein:
• solid material means fibers or microfibrils, as well as assemblies of fibers or fibers assembled in the form of a yarn, or in the form of a fabric made of yarns, weaved or knitted, for example, or also in the form of a nonwoven, or also in the form of a sheet of fibers forming an oriented matrix, or also in foam or powder form.
• a yarn designates a linear assembly of interconnected fibers (or of microfilaments).
• a cellulose yarn thus should be distinguished from a cellulose fiber, which designates an individual object, and not an assembly of objects.
• the solid material does not correspond to individualized fibers.
• a yarn is obtained by spinning of fibers of the same type, but may also be obtained by spinning of different fibers, such as for example, cellulose fibers in combination with synthetic fibers.
• the yarns are knit in a fabric.
• Different stitches can be envisaged, particularly jersey (conventionally knit with a 42-filament 220-dtex yarn) or crochet (advantageously knit with 40-filament 110-dtex yarn).
• the solid material is a textile.
• “textile” means an assembly of yarns or of fibers, advantageously attached together, forming a strong and insoluble entity.
• the textile may be a fabric, advantageously obtained by weaving or knitting of yarns, or a non-woven obtained by assembly of fibers.
• the polymer forming the fibers of the material according to the invention contains cellobiose units. It may for example be natural cellulose or modified cellulose.
• modified cellulose it advantageously is viscose, which corresponds to regenerated cellulose.
• the fibers used according to the invention are for example obtained from natural cellulose, that is, fibers directly originating from a plant, either by being harvested on the plant, or by being obtained by a mechanical processing of the plant, such as by a milling, pressing, crushing, and/or separation.
• the cellulose fibers also are modified cellulose fibers, that is, natural cellulose or solubilized natural cellulose, having reacted with a chemical component.
• cellulose fibers also includes, in the sense of the present invention, regenerated cellulose fibers, that is, fibers of natural cellulose, possibly modified, solubilized in a solvent, and then shaped back in the form of fibers.
• Example of natural cellulose fibers originating from plants are cotton, hemp, jute, or wood pulp. Such cellulose fibers may also be of bacterial origin.
• Expression “based on a polymer containing cellobiose units” means that this polymer forms the main, if not the single, ingredient of the material. It is however not excluded for the material to contain other components, for example at least another polymer containing no cellobiose units such as polymers forming synthetic fibers. In a specific embodiment, other polymers possibly containing anhydroglucose units may be associated, such as alginate, hyaluronic acid, starch, or other glycosaminoglycans.
• Polymer containing cellobiose units designates a polymer which comprises at least two cellobiose units in its chain, and in a limiting case which is only formed of cellobiose units, such as cellulose.
• said polymer is modified, at least partially, at the level of its cellobiose units.
• At least some of the cellobiose units have at least one of the two primary alcohol functions, attached to the C 6 carbon, oxidized into a carboxylic acid function.
• the function attached to the C 6 carbon is either an alcohol function, or a carboxylic acid function.
• the cellobiose units have at least one of the two rings open between C 2 and C 3 .
• the C 2 and C 3 carbons may be unmodified, that is, they form a ring and have an alcohol function attached thereto.
• the presence of a ketone function at the C 2 and/or C 3 level is advantageously excluded.
• the ring between the C 2 and C 3 carbons may be open.
• the C 2 and/or C 3 carbons may have aldehyde and/or carboxylic functions, possibly functionalized, attached thereto. Acetal and semi-acetal functions, resulting from the reaction of alcohol groups with aldehyde groups, may also be present.
• these two characteristics should be present in the polymer, at the level of at least one cellobiose unit or possibly at the level of at least two different cellobiose units, each having one of the two above-described characteristics.
• the polymer containing cellobiose units is cellulose or viscose
• the polymer forming the material according to the invention thus is a derivative of cellulose or of viscose, more precisely an oxidized derivative.
• the first characteristic can be given to the material by submitting it to the action of an oxidizing mixture comprising a hypohalite, a halite, and an oxoammonium salt or a precursor of said salt.
• an oxidizing mixture comprising a hypohalite, a halite, and an oxoammonium salt or a precursor of said salt.
• any method of converting the primary alcohol group attached to the C 6 carbon exclusively into a carboxylic acid group is a possible alternative to the use of the above-described oxidizing mixture.
• the polymer present thus corresponds to a polyglucuronic acid.
• this first step would enable to control the acidity of the fabric, which is an important property for haemostasis.
• the obtained material is poorly absorbable, which property is improved due to the implementation of the second step of the method according to the invention:
• the opening of the ring between the C 2 and C 3 carbons is obtained by submitting the material to the action of a solution of periodic acid or of a salt thereof.
• any alternative method enabling to open the ring between C 2 and C 3 and to oxidize the alcohol functions attached to these carbons may be implemented.
• the periodate treatment causes, in addition to the opening of the ring between the C 2 and C 3 carbons, the oxidation of the alcohol functions attached to these carbons into aldehyde functions.
• Such functions may be used for the grafting of molecules of interest, such as enzymes, thus enabling to functionalize the material.
• aldehyde functions may be converted into carboxylic acid functions.
• the carboxylic acid functions may also be functionalized, to generate, for example, ester or amide functions.
• the material according to the invention is rich in carboxylic acid functions which may be attached to:
• carboxylic acid functions may be in protonated form or in the form of carboxylate ions, for example, complexed with calcium.
• the general oxidation degree or rate of the material according to the invention which corresponds to the conversion of the alcohol and/or aldehyde functions into carboxylic acid functions, is greater than 10%, advantageously greater than 12%, or even greater than 15%.
• the oxidation degree or rate is defined as the mass of the carboxylic acid groups contained in 100 g of the material.
• the measurement of the oxidation of the polymer, particularly of the cellulose may be for example evaluated by titrimetry, according to the protocol described by Sobue and Okubo by using the methodology described in the US pharmacopeia, by nuclear magnetic resonance (NMR) (Kumar et al.), or also by infrared spectrometry (Fujisawa et al.).
• the polymer should have the two previously-mentioned characteristics.
• the polymer chain should have:
• a solid material particularly in textile form and having the above-discussed structural characteristics, can be used as a medical compress, capable of having the expected properties in terms of mechanical stability, or aging strength, of haemostatic properties, and or absorbability.
• mechanical stability designates the fact that the material can be handled with tools, particularly pliers, or even manually, while keeping a good mechanical behavior.
• the mechanical stability also gives the material the property of being capable of being kept in store for several months, or even several years, at ambient temperature, without for its integrity to be altered.
• haemostatic means the fact that the material is capable of stopping bleeding when it is locally applied.
• absorption means the fact that the material is totally or mainly degraded in vivo 2 weeks after implantation, advantageously after 1 week.
• the absorption may be quantified visually, by observing the degree of degradation of the material, or by any other adapted method, such as histology, for example.
• the material according to the invention has an adjustable absorbable character.
• it may be implanted for variable durations: a short-term implantation, translating as a total absorption of the material at the end of a maximum time period of 30 days, or a long-term implantation translating as a complete absorption of the material at the end of a time period longer than 30 days.
• the present invention is advantageous in the medical field, said material being usable as a compress, implantable dressing, prosthesis, vascular endoprosthesis or recellularization matrix, for an organ implant or regeneration.
• a compress may be in sponge or textile form.
• a compress preferably corresponds to a textile obtained by means of the claimed method.
• the primary use of the solid material according to the invention depends on the type of material present:
• the invention aims at a method providing a solid material based on a polymer having its cellobiose units exhibiting the following characteristics:
• this method comprises the steps of:
• the present invention aims at a method of processing a solid material based on polymer containing cellobiose units comprising the following steps:
• the material thus processed is placed in contact with a halite solution.
• This method may be implemented either directly on the already shaped material, that is, a textile, either on yarns which will then be weaved or knit, or even on fibers which will then be associated by electrospinning or carding/interlocking in the form of nonwoven, oriented or not, or of yarns.
• the method according to the invention is implemented on a solid material having its final form advantageously in the form of a textile.
• the first step may be implemented on fibers which may, between the 2 steps, be assembled in nonwoven or yarn form.
• the first step may be carried out on yarns which will then be knit or woven, the second step being carried out on the knitted fabric or the woven fabric.
• the material may be submitted to a finish removal step enabling to remove the fat used in spinning.
• This fat is essentially formed of yarning oils and of acrylate glue coating the filaments.
• Different finish removal protocols are known in prior art and may be implemented.
• the solid material based on polymer comprising cellobiose units comprises no oxidized cellulose.
• “Comprising no oxidized cellulose” means, in the sense of the present invention, having a degree of oxidation smaller than 1%. This preferably relates to natural or synthetic cellulose fibers, or synthetic fibers or also natural fibers possibly containing cellulose, but comprising no oxidized cellulose, that is, having received no specific oxidizing processing.
• Synthetic fibers means fibers which have no natural precursor polymer, such as fibers obtained by polymerizing of a synthetic monomer, for example, a petroleum product.
• Synthetic fibers, absorbable or not particularly comprise polyamides such as nylons, polyesters, polyacrylates, polyurethanes, polylactic and polyglycolic acids, polyethylene glycols, poly- ⁇ -olefins, and halogenated polymers, the copolymers or combinations thereof.
• polyamides such as nylons, polyesters, polyacrylates, polyurethanes, polylactic and polyglycolic acids, polyethylene glycols, poly- ⁇ -olefins, and halogenated polymers, the copolymers or combinations thereof.
• the first step of the method according to the invention thus is that enabling to selectively oxidize at least one primary alcohol group located in position 6 of the cellobiose units present in the solid material.
• This first step is carried out in the presence of a hypohalite, of a halite, and of an oxoammonium salt or of a precursor of said salt, advantageously in aqueous solution.
• oxoammonium salt precursor designates a chemical species capable of generating an oxoammonium salt by reaction with one of the components of the oxidizing mixture, particularly by oxidation by one of the mixture components.
• Oxoammonium salts are water-soluble oxidizers capable of selectively oxidizing primary alcohols, when the reaction takes place in appropriate pH and temperature conditions.
• Oxoammonium salts preferred according to the invention are di-tert-alkyl salts, particularly 1-oxo-2,2,6,6-tetramethylpiperidine-1-oxyde salts, commonly called TEMPO, and the derivatives thereof.
• the oxoammonium salts which catalyze this first partial oxidation step, are regenerated in situ by a secondary or auxiliary oxidizing system, in the case in point in the presence of a hypohalite, preferably sodium hypochlorite (NaClO).
• a hypohalite preferably sodium hypochlorite (NaClO).
• NaClO sodium hypochlorite
• the latter is in turn regenerated in situ by the reaction of a halite, preferably sodium chlorite NaClO 2 , after it has reacted with the aldehydes newly formed by oxidation of the primary alcohol in position 6.
• the first oxidation step is carried out in the presence of a substoichiometric quantity of oxoammonium salt or of a precursor thereof with respect to the quantity of anhydroglucose units present in the processed material.
• the oxoammonium salt or a precursor thereof amounts to from 0.0003 to 0.0006 mole per gram of polymer containing cellobiose units (cellulose).
• the quantities of reactants mentioned in the description correspond to the specific case where the polymer containing cellobiose units is cellulose. Thus, in the case of a mixture of polymers or of polymers which do not only have cellobiose units, these quantities are calculated according to the number of cellobiose units present.
• the first oxidation step is carried out in the presence of a hypohalite quantity substoichiometric with respect to the quantity of anhydroglucose units present in the processed material, advantageously from 0.0006 to 0.0049 mole of hypohalite per gram of polymer containing cellobiose units (cellulose). Typically, a quantity of 0.0012 mole of hypohalite per gram of polymer containing cellobiose units (cellulose) is used.
• the first oxidation step is carried out in the presence of a stoichiometric excess of halite with respect to the quantity of anhydroglucose units present in the processed material, advantageously from 0.006 to 0.025 mole of halite per gram of polymer containing cellobiose units (cellulose). Typically, a quantity of 0.012 mole of halite per gram of polymer containing cellobiose units (cellulose) is used.
• the 3 components are present in the oxidizing mixture since the beginning of the reaction.
• the oxidizing mixture is formulated in demineralized water, to avoid altering the ionic force and the pH.
• the first oxidation step is advantageously carried out in a reaction medium having a neutral, or even slightly acid pH, advantageously in the range from 5 to 7.
• this reaction is carried out at a pH in the range from 5 to 7.
• this oxidation step is preferably carried out at a temperature greater than 40° C., advantageously in the order of 60° C.
• this oxidation reaction takes place for a duration in the range from 1 to 6 hours, advantageously from 4 to 5 hours.
• the material obtained at the end of this first step has an oxidation rate in the range from 10 to 16%, advantageously in the range from 12 to 15%.
• a radical way to stop the oxidation reaction is to add to the reaction medium a primary alcohol, such as an excess of ethanol which will react with the oxoammonium salt and considerably dilute by mass effect the reaction with cellulose.
• this first step it may be useful to protonate the carboxylic acid functions present in the material thus processed.
• this step is carried out by incubation of the material in a protonation medium.
• This is advantageously performed by incubation in hydrochloric acid (HCl), advantageously in one or a plurality of HCl baths from 0.1 to 1 mol/l (N), for a plurality of hours.
• HCl hydrochloric acid
• the oxidation medium may be eliminated by discharge and replaced with the protonation medium.
• the material is advantageously washed and dried.
• the compress is advantageously washed in a medium containing a solvent and/or water.
• An alcohol and/or demineralized water and/or acetone form a preferred washing medium, for example, ethanol at 50% and then ethanol at 95%.
• washings may be repeated and generally last for a few hours, advantageously from 1 to 10 hours.
• the material thus processed is dried by any adapted means, particularly with static or dynamic air or also in vacuum, and this, advantageously, for a plurality of hours.
• the second oxidation step is carried out in the presence of periodic acid, or of a salt thereof, in the reaction medium.
• the material is incubated in a solution of periodic acid, or of a salt thereof. It advantageously is an aqueous solution.
• the periodate ion is known to split glycols and turn them into dialdehydes. Thereby, the polymeric chain is not cut, but rather acquires a greater flexibility by opening of the rings.
• the periodic acid or a salt thereof is present by up to from 0.003 to 0.012 mole per gram of polymer containing cellobiose units (cellulose), advantageously 0.006 mole par gram de polymer containing cellobiose units (cellulose).
• the periodic acid salt is sodium periodate.
• the second oxidation step is carried out at a pH in the range from 2 to 5, advantageously equal to 3.
• this second step is carried out at a temperature in the range from 5 to 60° C., advantageously equal to 35° C.
• the conventional duration of this step is advantageously in the range from 1 to 6 hours, advantageously equal to 3 h.
• this reaction occurs away from light.
• a third oxidation step may be implemented on the solid cellulosic material having undergone the first two oxidation steps.
• This third step is then carried out in the presence of a halite, advantageously in the presence of an aqueous halite solution.
• This step enables to selectively oxidize the aldehyde functions obtained after the reaction to periodate into carboxylic acid functions.
• the halite is a chlorite, and more preferably sodium chlorite.
• the solution comprises from 0.0025 to 0.012 mole of halite per gram of polymer containing cellobiose units (cellulose), advantageously 0.006 mole per gram of polymer containing cellobiose units (cellulose).
• the third step is carried out at a pH in the range from 5 to 7, advantageously equal to 5.8.
• the temperature at which this reaction takes place is advantageously greater than 15° C., more advantageously still equal to 35° C. As a variation, it may be carried out at ambient temperature.
• the third reaction of oxidation of the cellulosic material is carried out for a duration in the range from 0.25 to 2 hours, advantageously from 0.5 to 1 hour.
• the conversion of the aldehyde functions into carboxylic acid functions enables, due to the measurement of the oxidation rate, to quantify the reaction occurring at the second step of the method according to the invention.
• the combination of steps 2 and 3 enables to increase the oxidation rate by from 1 to 7%, advantageously from 2 to 4%.
• the oxidation of the cellobiose units occurs according to the following scheme:
• the material is washed in a bath of distilled water and/or of ethanol and/or of acetone, possibly repeatedly. It is then advantageously dried as described hereabove.
• a material based on oxidized cellulose should exhibit carboxylic acid functions, either protonated, or complexed with calcium ions (Ca 2+ ), to develop the desired haemostatic properties.
• the processed material is submitted to one or a plurality of washings, advantageously with ethanol, and to a drying, carried out in the above-described conditions.
• the method according to the invention capable of being implemented on any solid material, and particularly on a textile, has many advantages, including the following:
• This step enables to partially oxidize the cellulose via the conversion of primary alcohol functions attached to the C 6 carbon of the cellobiose units into carboxylic acid functions.
• 10 g of knitted regenerated cellulose are then placed in the NaClO 2 solution.
• 0.006 mole of TEMPO and an aqueous solution of NaClO with 2% of active chlorine (0.012 mol) are then added to the reaction mixture.
• the total volume of the reaction mixture is 500 ml.
• the Erlenmeyer is closed and placed in a thermostatic water bath maintained at a 60° C. temperature for a duration from 1 to 6 h, and typically from 4 to 5 h. The oxidation is stopped by addition of an excess of ethanol.
• the partially oxidized cellulose fabric is wrung and then incubated for 12 h in an aqueous solution of N HCl on an orbital shaker.
• the aqueous solution of N HCl is renewed and the incubation is carried on for 2 h.
• the partially oxidized cellulose fabric is wrung and then washed with 50% ethanol for 1 h on an orbital shaker. This operation is repeated twice.
• the fabric is then wrung, and then washed with 95% ethanol for 1 h on an orbital shaker, and then finally wrung and air-dried under a ventilator for at least 12 h.
• This step enables to open the ring between the C 2 and C 3 carbons of the cellobiose units. Simultaneously, the alcohol functions attached to these carbons are oxidized into aldehyde functions.
• NaIO 4 (mole per gram of cellulose) from 0.003 to 0.012, for example 0.006 pH of the reaction medium from 2 to 5, for example 3 Temperature (° C.) from 5 to 60, for example 35 Duration of the reaction (h) from 1 to 6, for example 3
• This step enables to oxidize the aldehyde functions attached to the C 2 and C 3 carbons of the cellobiose units into carboxylic acid functions.
• NaClO2 (mole per gram of from 0.0025 to 0.012, for example 0.006 cellulose) pH of the reaction medium from 5 to 7, for example 5.8 Temperature (° C.) greater than 15° C., for example, 35° C. Duration of the reaction (h) from 0.25 to 2, for example 1
• the intensity of this coloring has been graded for different products: from 0 for a solution having no purple coloring to +++ for a very intense purple solution.
• the degree of oxidation of the partially oxidized cellulose fabric represents the mass of carboxylic acid groups contained in 100 g of said fabric. This value is measured by titrimetry, according to the calcium exchange method described by Sobue and Okubo, and recommended by the United States Pharmacopeia (USP, 1990).
• test 1 crochet; test 2: jersey
• test 2 jersey
• the oxidation rate is sufficient for the material obtained by means of the method according to the invention to have good haemostatic properties.
• the obtained partially oxidized cellulose fabric keeps an excellent mechanical resistance after 1 month, in a stove at 60° C.
• This sample keeps a fine aspect, with no degradation.
• This same sample has been sterilized by irradiation with ⁇ rays, and has then been submitted to an aging process which has caused no degradation of the fabric.
• a stability equivalent to that of the Surgicel® product has also been observed after 3 month at 25° C. and in controlled humidity, or after a 60° C. thermal stress.
• the method according to the present invention results in a material (tests 1 and 2) with an apparent polymerization degree, measured by the viscosity, of the same order as the reference product (Surgicel®).
• the rats After 14 days, the rats have been sacrificed by inhalation of CO 2 . The products have been taken off and the implantation sites have been removed and macroscopically analyzed.
• the presence of a necrosis, of an exudate, of a neovascularization, and of an encapsulation have been evaluated at the implantation site, by means of a scoring chart.
• the rating scale is the following: absent (0); light reaction (1); moderate reaction (2); strong reaction (3); severe reaction (4).
• the scale is the following:
• test products are mainly absorbed; for product Test1, 3 sites are totally absorbed out of 4 and 1 site has small fragments; for product Test2, 3 sites are not absorbed; finally, for the control product, 2 sites out of three are absorbed and 1 site exhibits a moderate persistence.
• the material obtained by the method according to the invention has a absorption speed comparable to reference commercial product Surgicel®, and even better, if it is considered that the fabric used in this study has a grammage greater than that of Surgicel®.
• the haemostatic performance has been tested on the processed cellulosic textile on animals on a per-operative bleeding model versus reference product Surgicel®.
• the methodology comprises creating, on pigs, lesions of square shape and of predetermined surface area on organs (spleen and liver) and then to cover the wounds thus created with the compresses to be tested.
• a haemostatic behavior of the tested cellulosic textile comparable to that of the reference product can be observed, whatever the tested organ: the behavior in contact with blood is identical to that of the reference and the time necessary to obtain the stopping of the bleeding is equivalent for each considered organ.
• the textile has disappeared from the reaction medium.
• the reaction medium is then precipitated in the presence of ethanol but the obtained precipitate is inexploitable.

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• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Chemical & Material Sciences (AREA)
• Textile Engineering (AREA)
• Life Sciences & Earth Sciences (AREA)
• Materials Engineering (AREA)
• Public Health (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Hematology (AREA)
• Veterinary Medicine (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Medicinal Chemistry (AREA)
• Polymers & Plastics (AREA)
• Organic Chemistry (AREA)
• Biochemistry (AREA)
• Polysaccharides And Polysaccharide Derivatives (AREA)
• Materials For Medical Uses (AREA)
• Polyesters Or Polycarbonates (AREA)

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• 2012
  • 2012-06-04 FR FR1255182A patent/FR2991328B1/fr active Active
• 2013
  • 2013-06-03 EP EP13730029.9A patent/EP2855534B1/fr active Active
  • 2013-06-03 CN CN201380029400.9A patent/CN104411726B/zh active Active
  • 2013-06-03 BR BR112014030275A patent/BR112014030275B8/pt active IP Right Grant
  • 2013-06-03 WO PCT/FR2013/051255 patent/WO2013182798A1/fr active Application Filing
  • 2013-06-03 JP JP2015515568A patent/JP6421116B2/ja active Active
  • 2013-06-03 US US14/404,842 patent/US20150147558A1/en not_active Abandoned
  • 2013-06-03 ES ES13730029.9T patent/ES2594327T3/es active Active
• 2019
  • 2019-07-10 US US16/507,768 patent/US11214917B2/en active Active

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