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
  • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
  • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
  • A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
  • A61L31/129—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing macromolecular fillers
• • 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
  • A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• • 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
  • A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
  • A61L17/005—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters containing a biologically active substance, e.g. a medicament or a biocide
• • 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
  • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
  • A61L24/001—Use of materials characterised by their function or physical properties
  • A61L24/0015—Medicaments; Biocides
• • 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
  • A61L26/0066—Medicaments; Biocides
• • 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
  • A61L27/54—Biologically active materials, e.g. therapeutic substances
• • 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
  • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
  • A61L31/04—Macromolecular materials
  • A61L31/042—Polysaccharides
• • 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
  • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
  • A61L31/04—Macromolecular materials
  • A61L31/048—Macromolecular materials obtained 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
  • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
  • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
  • A61L31/16—Biologically active materials, e.g. therapeutic substances
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • 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
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
  • A61L2300/202—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with halogen atoms, e.g. triclosan, povidone-iodine
• • 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
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
  • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents

Definitions

• the present invention relates to a new antiseptic and biodegradable composite material, comprising the complex of povidone-iodine or iodopovidone (hereinbelow, PVPI) and alginate, and to medical devices produced with the use of the above-mentioned composite material.
• PVPI povidone-iodine or iodopovidone
• the povidone-iodine complex is a water-soluble complex of iodine and polyvinylpyrrolidone widely used for its bactericide and fungicide properties.
• PVPI is known for its iodo- phor properties, i.e., as a substance acting as a vehicle or solubilizer for iodine and which is able to release into solution small amounts of free iodine, minimizing the toxicity thereof and preserving the moderate germicide activity of that element.
• the most common form of the PVPI complex is its aqueous solution containing from 9% to 12% of available iodine (calculated on the anhydrous basis); aqueous solutions of PVPI are directly applied to open wounds or infected regions, a method commonly known as wound irrigation. While the low release of iodine from the PVPI complex into solution mi ⁇ nimizes the toxicity of iodine for mammal cells, its quick absorption by open wounds dur ⁇ ing irrigation may cause severe toxicity problems, thus limiting the surgical applications thereof, particularly for repeated applications.
• PVPI is also used internally, for example on burns, large wounds, deep tissues, or mucosae.
• PVPI polyethylene glycol
• PEG has the drawback to be a synthetic, non-biodegradable polymer.
• An object of the present invention is to provide new biodegradable materials su i table for a controlled release of PVPI.
• Another object of the invention is to provide materials suitable for producing med i cal de ⁇ vices, and particularly of PVPI dispensing systems for use in the treatment of internal and external wounds, with PVPI controlled release properties.
• a special object of the invention is to provide a medical device in the form of a self- supporting film for the PVPI release, useful as an antiseptic dressing for wounds.
• Another object of the invention is to provide antiseptic filling systems, for internal and ex ⁇ ternal use, of open wounds, particularly in the form of microcapsules.
• a further object of the invention is to provide medical devices in the form of ant i sept i c and biodegradable surgical suture threads.
• the invention provides composite materials consisting of, or compr i s i ng, a ma ⁇ trix of alginate in which the iodopovidone complex is dispersed.
• the alginates used according to the invention are straight, non-branched polysacchar i des, containing different proportions of ⁇ -D-mannuronic acid (M) and residues of o-L- guluronic acid (G).
• M ⁇ -D-mannuronic acid
• G o-L- guluronic acid
• the M and G monomers are linked in the 1-4 position through glyco ⁇ side linkages, forming homopolymeric MM or GG blocks which are interspersed w i th he- teropolymeric MG or GM blocks.
• the molecular variability of these polymers depends on the source of seaweeds, from the tissues of which the alginates are extracted; among alginates, sodium alginate was w i dely considered as a non-toxic, natural material with properties of interest for drug dispens i ng systems. Since it is hydrophilic and biodegradable, it can be absorbed by the sk i n i nto bo- dily fluids without toxic effects, so as to be highly beneficial in the wound healing and ci ⁇ catrization process.
• the composite material according to the invention combining an alginate with PVPI, allows obtaining medical devices and PVPI dispensing systems achieving a synergic effect on wounds.
• Alginate provides a healing effect
• PVPI provides an antiseptic effect.
• alginate can be used in the form of soluble alginate, such as, for example, sodium or potassium alginate, or in the form of cross-linked, water- insoluble alginate, such as calcium alginate.
• the composite material that is the subject-matter of the invention can be a preferably substantially anhydrous composition, comprising or consisting of 55-80% by weight of alginate and from 45% to 20% by weight of PVPI, preferably from 60% to 76% by weight of alginate and from 40% to 24% by weight of PVPI, or more preferably from 65% to 75% by weight of alginate and from 35% to 25% by weight of PVPI.
• the matrix material and the medical devices produced therewith consist essentially of alginate and PVPI in the weight ratios indicated above.
• the composite material does not comprise other polysaccharides beside algi ⁇ nate, and particularly polysaccharides, such as sucrose, forming liquid systems with PVPI and which can thus give rise to deteriorations, losses or infiltrations, optionally increasing the patient's glycemic index.
• polysaccharides such as sucrose
• the composite material and the medical devices produced therewith are particularly useful for the treatment of diabetic ulcers and for diabetic pa- tients, since alginate does not increase the diabetic conditions, but it is able to control and regulate them.
• the composite material may comprise other substances that are suitable for altering the mechanical properties of the material, for use in the production of specific biomedical devices.
• the material may comprise plasticizers, particularly glycerol, proteins or peptides (for example, gelatin), essential oils, surfactants, polyethylene glycol or a combination thereof, suitable to confer to the composite material the appropriate mechanical properties necessary for the production of the medical devices of interest.
• plasticizers particularly glycerol, proteins or peptides (for example, gelatin), essential oils, surfactants, polyethylene glycol or a combination thereof, suitable to confer to the composite material the appropriate mechanical properties necessary for the production of the medical devices of interest.
• self-supporting films useful as a wound dressing, can be produced by using a composition comprising sodium alginate as a matrix material, PVPI as a dispersed material, and glycerol as a plasticizer.
• the plasticizer as well as any of the materials indicated above, can be comprised in the composition in amounts, for example from 5% to 35% by weight, referred to the total weight of the alginate/PVPI material, more preferably from 20% to 30% by weight.
• a cross-linked calcium alginate As a matrix material, it is preferable to use a cross-linked calcium alginate as a matrix material.
• Films useful as a wound dressing, microcapsules ("beads”) and suture threads can be obtained by the following preparative examples.
• fig. 1 shows veins of films after 48 incubation with the following compositions: pure NaAlg (a); NaAlg 70%, 30% glycerol (plasticizer) film (b); NaAlg 57%, 25% glycerol, 18% PVPI film (c), 52% NaAlg, 22% glycerol, 26% PVPI (d), 48% NaAlg, 20% glycerol, 32% PVPI; two identical films were incubated in plastic Petri capsules containing Candida albicans fungi for all the experiments.
• fig. 2 shows in the box (A) the growth curves for E.
• fig. 3 is a dynamic release scheme for 1 g PVPI (line with rhombi) and from 8 g (line with squares) of calcium alginate beads in water; PVPI release is quicker (within 15 minutes) in the solution containing 1 g of beads than that containing 8 g.
• alginic acid sodium salt having a viscosity of 15000-20000 cps, glycerol > 99.5 (GC) and anhydrous sodium chloride (all purchased from Sigma-Aldrich);
• the films were prepared as follows: 10 ml distilled water with 0,3 g NaAlg were mixed and heated by using a hot plate during 1 hour up to about 100° C, to ensure the complete dissolution of alginate in water.
• the viscous solution was let to cool to room temperature, and 0.1 ml glycerol as the plasticizer was added.
• the amount of added glycerol was kept constant in all the successive preparations of the solution.
• Different volumes (1.0 ml, 1.5 ml, and 2.0 ml) of a PVPI aqueous solution were slowly mixed to the NaAlg/glycerol solutions.
• the final solutions were mixed by using a Vortex mixer and left to rest for a period of time to ensure the absence of bubbles in the vials.
• the prepared solutions were poured dropwise on substrates of 1 cm 2 and left at laboratory room temperature to dry. According to the above-mentioned procedure, the following films were prepared:
• film 1 57% NaAlg, 25% glycerol, and 18% PVPI;
• film 2 52% NaAlg, 22% glycerol, and 26% PVPI;
• film 3 48% NaAlg, 20% glycerol, and 32% PVPI.
• Example 2 Preparation of calcium alginate microcapsules ("beads") and of sutures containing PVPI
• the above-mentioned solution which was used for the production of the film 3 (48% NaAlg, 20% glycerol, and 32% PVPI), was used for preparing CaAlg/PVPI beads and suture threads, respectively.
• the NaAlg/PVPI solution was introduced by dipping dropwise or, respectively, for the production of suture threads, it was continuously supplied by a syringe in a 10% calcium chloride solution in distilled water. The formation of the beads and the suture threads was immediate; however, the so-obtained products were left in the calcium chloride solution during 30 minutes to ensure a high cross-linking.
• the cross-linking time may be varied in order to obtain a higher or lower cross-linking, as a function of the desired application.
• Example 3 Test to assess the antibacterial/antimycotic activity of sodium alginate/PVPI films
• an E. Coli culture incubated overnight with a final concentration of 8 x 10 8 cells/ml was diluted to final concentration of 10 6 cells/ml, and 500 of this solution were deposited on a plate with fresh Luria-Bertani (LB) culture medium.
• LB Luria-Bertani
• the plates were placed in an incubator at 37° C for two hours (to allow the evaporation of the residual culture medium) and the different substrates (two for each LB plate) were placed.
• the initial inoculum of 10 8 cells/ml was diluted to 10 5 cells, and 100 ih of this solution were deposited on a fresh Sabouraud dextrose agar (SDA) culture medium.
• SDA Sabouraud dextrose agar
• the sodium alginate/PVPI films with the following compositions (a) pure sodium alginate (b) 70% NaAlg, 30% glycerol (plasticizer); (c) 57% NaAlg, 25% glycerol, 18 % PVPI; (d) 52% NaAlg, 22% glycerol, 26 % PVPI; (e) 48% NaAlg, 20% glycerol, 32 % PVPI were prepared and tested after 24 hours incubation; films with the following compositions were tested after 24 hours incubation: (f) 57% NaAlg, 25% glycerol, 18 % PVPI; (g) 52% NaAlg, 22% glycerol, 26 % PVPI and (h) 48% NaAlg, 20% glycerol, 32 % PVPI.
• the PVPI complex is very active even when it is incorporated in the NaAlg matrix. Furthermore, the formation of an inhibition area around all the films containing PVPI complexes indicates that PVPI is released from the NaAlg matrix, thus making these compounds not only surface active, but also inhibitory.
• Films of pure NaAlg and glycerol-plastified NaAlg were both invaded by the fungi, as seen in Figs. 1 (a) and 1 (b), while the films containing the PVPI complex show areas on the surface thereof that are free from fungi, as well as a large inhibition area around them, as shown in fig. 1 (c), 1 (d), and 1 (e).
• Example 4 Test for verifying the antibacterial/antifungal activity of calcium algi- nate/PVPI beads
• Microcapsules of calcium alginate/PVPI obtained according to the procedure of the example 2 by depositing droplets of NaAlg/PVPI aqueous solutions in a container containing an excess of CaCl 2 dissolved in water were tested for their antibacterial and antimycotic activity.
• the obtained beads have an average dimension of about 3 mm.
• the calcium alginate beads allow the complete encapsulation of the PVPI complex in water, while the same amount of PVPI complex is immediately released in water after the dropwise addition.
• the antibacterial/antimycotic properties of the calcium alginate/iodopovidone beads were tested by a turbidity assay. Particularly, a C. albicans culture incubated overnight and which reached confluence was diluted to an OD 60 o of 0.1, then 1 g of calcium alginate/PVPI beads was added to the culture, and the optical density at 600 nm was measured every 30 minutes with a spectrophotometer (Thermo Scientific).
• the growth curves of fungi C. albicans which contacted the aqueous solution containing 1 g of CaAlg beads are similar to those of the control, consisting in water only.
• the curve relative to fungi growing with 1 g of calcium alginate/iodopovidone beads shows that the cell population never starts to grow, thus indicating the cell death.
• the same results were obtained with E. coli cultures as shown in Fig. 2B, but a higher amount of sodium alginate/iodopovidone beads, i.e., 12 g, was necessary to stop the bacterial growth. This is because the minimum bactericidal concentration of 2 x 10 "3 M iodopovidone was higher than the respective minimum fungicidal concentration of 1 x 10 "3 M.
• MBC minimum bactericidal concentration
• MFC minimum fungicidal concentration
• the release from the solution containing 1 g of beads reaches more quickly the release plateau (within 25 minutes) compared to a solution containing 8 g of CaAlg/PVPI beads.
• the controlled release characteristics of the beads combined with the antiseptic properties, biocompatibility and biodegradability thereof, make such beads particularly suitable in clinical applications as internal and external antiseptic fillers for wounds, and do not require removal interventions.
• the threads obtained by the procedure of the example 3 can be used as suture threads for surgical sutures.
• sutures have antimicrobial properties suitable to significantly reduce the infection risk of the wound after surgery.
• sutures are also biodegradable, they are ideal for those patients who do not need to be re-hospitalized for suture removal. Biodegradation times turn out to be sufficient to allow healing, while maintaining the required bonding function.
• the described composite materials find application as antimicrobial coatings, or as packaging materials for food and biomedical industries, as well as acting as purification and sterilization materials against bacterial contaminations.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Epidemiology (AREA)
• Materials Engineering (AREA)
• Surgery (AREA)
• Vascular Medicine (AREA)
• Medicinal Chemistry (AREA)
• Biomedical Technology (AREA)
• Molecular Biology (AREA)
• Heart & Thoracic Surgery (AREA)
• Dermatology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Transplantation (AREA)
• Hematology (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Composite Materials (AREA)
• General Chemical & Material Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Organic Chemistry (AREA)
• Materials For Medical Uses (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Compositions Of Macromolecular Compounds (AREA)

Priority Applications (4)

Applications Claiming Priority (2)

Publications (1)

Family

ID=46584198

Family Applications (1)

Country Status (6)

Cited By (5)

Families Citing this family (2)

Citations (4)

Family Cites Families (12)

• 2012
  • 2012-03-21 IT IT000258A patent/ITTO20120258A1/it unknown
• 2013
  • 2013-03-21 JP JP2015501043A patent/JP6157582B2/ja not_active Expired - Fee Related
  • 2013-03-21 EP EP13721090.2A patent/EP2827912B1/en active Active
  • 2013-03-21 US US14/384,591 patent/US9931444B2/en active Active
  • 2013-03-21 CA CA2866782A patent/CA2866782C/en active Active
  • 2013-03-21 WO PCT/IB2013/052245 patent/WO2013140362A1/en not_active Ceased

Patent Citations (4)

Also Published As

Similar Documents

Legal Events