WO2001043787A2 - A process for preparing an autologous platelet gel and membrane thereof - Google Patents

A process for preparing an autologous platelet gel and membrane thereof Download PDF

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Publication number
WO2001043787A2
WO2001043787A2 PCT/EP2000/012661 EP0012661W WO0143787A2 WO 2001043787 A2 WO2001043787 A2 WO 2001043787A2 EP 0012661 W EP0012661 W EP 0012661W WO 0143787 A2 WO0143787 A2 WO 0143787A2
Authority
WO
WIPO (PCT)
Prior art keywords
membrane
process according
platelet
anyone
batroxobin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2000/012661
Other languages
English (en)
French (fr)
Other versions
WO2001043787A3 (en
WO2001043787B1 (en
Inventor
Maria Cristina Sacchi
Marco Bellanda
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to AU25111/01A priority Critical patent/AU2511101A/en
Priority to CA2393315A priority patent/CA2393315C/en
Priority to DK00988792T priority patent/DK1239895T3/da
Priority to DE60002231T priority patent/DE60002231T2/de
Priority to AT00988792T priority patent/ATE237370T1/de
Priority to US10/129,827 priority patent/US6841170B2/en
Priority to JP2001544923A priority patent/JP2003516815A/ja
Priority to EP00988792A priority patent/EP1239895B1/en
Publication of WO2001043787A2 publication Critical patent/WO2001043787A2/en
Publication of WO2001043787A3 publication Critical patent/WO2001043787A3/en
Publication of WO2001043787B1 publication Critical patent/WO2001043787B1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0057Ingredients of undetermined constitution or reaction products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/14Alkali metal chlorides; Alkaline earth metal chlorides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14Blood; Artificial blood
    • A61K35/19Platelets; Megacaryocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/48Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482Serine endopeptidases (3.4.21)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/0005Ingredients of undetermined constitution or reaction products thereof

Definitions

  • the present invention relates to a process for preparing an autologous platelet gel and membranes thereof, and a kit for carrying out this process. Background of the invention
  • the platelet concentrate is prepared by carrying out a venous blood sample of 500 ml, namely an operation which is accomplished by means a venous catheter.
  • the platelet concentrate is subsequently activated with calcium chloride and bovine thrombin to produce a platelet gel which can be combined with either autologous spongy and cortical bone or bone matrix consisting of bio-glasses.
  • the Applicant has unexpectedly found that it is possible to overcome the aforementioned drawback, by using as the activator batroxobin in place of thrombin.
  • the present invention therefore relates to a process for preparing a platelet gel comprising mixing a platelet concentrate with an inorganic or organic calcium salt and batroxobin.
  • a further object of the present invention relates to a kit for carrying out the process according to the present invention which in particular comprises: a) a monouse sterile capsule of transparent plastic or glass material, fitted with a screw cap constituted in the upper part by a perforable membrane coated with a suitable sterile coating, said perforable membrane allowing the insertion of the needle of a syringe containing the platelet concentrate, and contemporaneously avoiding the air contact with the inside of the capsule, b) two plug injectors surmounting said perforable membrane containing respectively the calcium salt and batroxobin.
  • Figure 1 and 2 represent two preferred embodiments of the kit according to the present invention.
  • (3) represents the sterile monouse capsule, (4) the screw cap constituted in the upper part by a perforable membrane (5).
  • (1 ) and (2) represent the two plug injectors surmounting said perforable membrane (5).
  • the inorganic calcium salt used in the process according to the present invention is calcium chloride, whereas when an organic calcium salt is sued this is preferably calcium gluconate. According to a particularly preferred embodiment, the process is carried out by using calcium gluconate.
  • the inorganic or organic calcium salt is in the form of an aqueous solution containing it in amounts ranging from 5.10 "5 to 0.5 M. According to a preferred embodiment in the process of the present invention,
  • the batroxobin used is preferably in the form of an aqueous solution having 1 thrombin international unit and is sold under the commercial name Botropase by Ravizza Farmaceutici S.p.A.
  • the platelet concentrate used in the process according to the present invention is prepared from whole blood (sample of 40-50ml of venous blood), collected in 20ml syringes, containing 4 ml sodium citrate used as anticoagulant ), by a two phases centrifugation, thereby obtaining an intermediate product being platelet rich plasma. This method allows to recover at least 80% of platelets present in whole blood.
  • this technique encompasses the following steps. Venous blood is collected in 4 tubes and centrifuged at 180 g for 20 minutes. After this treatment two phases are obtained a dark one constituted by precipitated red and white cells at the bottom of the tubes, and a clear one visible in the upper part of the probe, consisting of platelet rich plasma.
  • This plasma is taken and transferred by means of a Pasteur pipette into other 4 tubes and centrifuged at 580 g for 20 minutes. Thanks to this faster centrifugation (580 g versus 180 g) it is possible to obtain platelets sedimentation as a dense small bottom said "pellet".
  • the liquid supernatant consists of platelet poor plasma.
  • the tubes are emptied, however leaving in each of them a small aliquot (1.5 ml) of platelet poor plasma necessary to suspend once again the "pellet” thereby obtaining a homogeneous suspension.
  • Membranes according to the present invention and method for preparing them may contain active principles such as antibacterial agents, disinfectants, and/or sterile excipients etc .
  • the membrane according to the present invention essentially consists of the autologous platelet gel according to the present invention.
  • the platelet gel preparation occurs in plastic or glass Petri dishes (like those utilised in cellular cultures), it is possible to obtain a thin membrane, as the gel during the activation takes the form of the container.
  • Figure 1 and 2 represent preferred embodiment of the kit according to the present invention.
  • (3) represents the sterile monouse capsule, (4) the screw cap constituted in the upper part by a perforable membrane (5).
  • This membrane is coated with a sterile coating normally used in phamaceutical and diagnositc industry such as aluminum film or another equivalent material.
  • (1 ) and (2) represent the two plug injectors surmounting said perforable membrane (5) and containing respectively the inorganic or organic calcium salt (more preferably 0.23 M calcium gluconate), and batroxobin.
  • Finally (6) represents the syringe containing the platelet concentrate, and (7) platelet gel formed during the reaction.
  • a manual pressure onto the cap injector (1 ) allows the outlet of calcium gluconate in amounts of from 0.3 to 0.5 ml into the capsule (3) .
  • a manual pressure onto the cap injector (2) allows the outlet of batroxobin in amounts of from 0.3 to 0.5 ml.
  • the capsule (3) reported in Figure 1 has preferably a capacity of from 10 to 20 ml, whereas the same capsule of the kit reported in figure 2 permits to obtain membranes of diameter of from 3 to 9 cm as the capsule may have a diameter ranging from 3.5 to 10.0 cm.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Materials Engineering (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Dermatology (AREA)
  • Surgery (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Materials For Medical Uses (AREA)
  • Surgical Instruments (AREA)
  • Compounds Of Unknown Constitution (AREA)
  • External Artificial Organs (AREA)
PCT/EP2000/012661 1999-12-14 2000-12-13 A process for preparing an autologous platelet gel and membrane thereof Ceased WO2001043787A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
AU25111/01A AU2511101A (en) 1999-12-14 2000-12-13 A process for preparing an autologous platelet gel and membranes thereof, and a kit for carrying out this process
CA2393315A CA2393315C (en) 1999-12-14 2000-12-13 A process for preparing an autologous platelet gel and membranes thereof, and a kit for carrying out this process
DK00988792T DK1239895T3 (da) 1999-12-14 2000-12-13 Fremgangsmåde til fremstilling af en gel af autologe blodplader
DE60002231T DE60002231T2 (de) 1999-12-14 2000-12-13 Verfahren zur herstellung eines gels von autologen blutplättchen
AT00988792T ATE237370T1 (de) 1999-12-14 2000-12-13 Verfahren zur herstellung eines gels von autologen blutplättchen
US10/129,827 US6841170B2 (en) 1999-12-14 2000-12-13 Process for preparing an autologous platelet gel and membrane thereof
JP2001544923A JP2003516815A (ja) 1999-12-14 2000-12-13 自己血小板ゲルとその膜を調製する方法、およびこの方法を実施するためのキット
EP00988792A EP1239895B1 (en) 1999-12-14 2000-12-13 A process for preparing an autologous platelet gel

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITAL99U000010 1999-12-14
IT1999AL000010U ITAL990010U1 (it) 1999-12-14 1999-12-14 Nuova metodica di laboratorio per preparare gel e membrane piastriniche ottenute dal concentrato piastrinico.

Publications (3)

Publication Number Publication Date
WO2001043787A2 true WO2001043787A2 (en) 2001-06-21
WO2001043787A3 WO2001043787A3 (en) 2001-12-13
WO2001043787B1 WO2001043787B1 (en) 2002-01-10

Family

ID=11333478

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/012661 Ceased WO2001043787A2 (en) 1999-12-14 2000-12-13 A process for preparing an autologous platelet gel and membrane thereof

Country Status (12)

Country Link
US (1) US6841170B2 (enExample)
EP (1) EP1239895B1 (enExample)
JP (1) JP2003516815A (enExample)
AT (1) ATE237370T1 (enExample)
AU (1) AU2511101A (enExample)
CA (1) CA2393315C (enExample)
DE (1) DE60002231T2 (enExample)
DK (1) DK1239895T3 (enExample)
ES (1) ES2197125T3 (enExample)
IT (1) ITAL990010U1 (enExample)
PT (1) PT1239895E (enExample)
WO (1) WO2001043787A2 (enExample)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003017913A1 (en) * 2001-08-27 2003-03-06 The Cleveland Clinic Foundation Compositions, methods and apparatus for surgical procedures
WO2004024198A1 (en) * 2002-09-10 2004-03-25 New Dawn-Consultores E Servicos Lda Activator for forming platelet gel, platelet poor plasma gel or platelet rich plasma gel
EP1652538A3 (en) * 2004-10-28 2007-01-31 Medtronic Vascular, Inc. Autologous platelet gel on a stent graft
WO2009121953A3 (en) * 2008-04-04 2010-02-25 Azienda Ospedaliero Universitaria Careggi Extracellular matrix comprising platelet factors
US9199007B2 (en) 2009-06-11 2015-12-01 Banc De Sang I Teixits Use of gelled PRP (platelet gel) for volumetric breast reconstruction
IT201700024672A1 (it) * 2017-03-06 2018-09-06 Caloprisco Gaetano Ditta Individuale Metodo e sistema per preparare un kit medicale per curare lesioni tissutali di un paziente

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US7992725B2 (en) 2002-05-03 2011-08-09 Biomet Biologics, Llc Buoy suspension fractionation system
US7832566B2 (en) 2002-05-24 2010-11-16 Biomet Biologics, Llc Method and apparatus for separating and concentrating a component from a multi-component material including macroparticles
US20030205538A1 (en) 2002-05-03 2003-11-06 Randel Dorian Methods and apparatus for isolating platelets from blood
US7845499B2 (en) 2002-05-24 2010-12-07 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US20060278588A1 (en) 2002-05-24 2006-12-14 Woodell-May Jennifer E Apparatus and method for separating and concentrating fluids containing multiple components
DE10392686T5 (de) 2002-05-24 2005-07-07 Biomet Mfg. Corp., Warsaw Vorrichtung und Verfahren zum Trennen und Konzentrieren von Flüssigkeiten, welche mehrere Komponenten enthalten
ITRM20030467A1 (it) * 2003-10-10 2005-04-11 Advance Holdings Ltd Contenitore monouso per la centrifugazione ed il trattamento di un materiale biologico fluido.
ES2426172T3 (es) * 2005-02-07 2013-10-21 Hanuman Llc Dispositivo concentrador de plasma
US7694828B2 (en) 2005-04-27 2010-04-13 Biomet Manufacturing Corp. Method and apparatus for producing autologous clotting components
US20070087061A1 (en) * 2005-10-14 2007-04-19 Medafor, Incorporated Method and composition for creating and/or activating a platelet-rich gel by contact with a porous particulate material, for use in wound care, tissue adhesion, or as a matrix for delivery of therapeutic components
US20070086958A1 (en) * 2005-10-14 2007-04-19 Medafor, Incorporated Formation of medically useful gels comprising microporous particles and methods of use
US8567609B2 (en) 2006-05-25 2013-10-29 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
ES2324438B1 (es) * 2006-06-19 2010-05-25 Lorente Alvarez-Beigbeder, S.L. Metodo para la obtencion de plaquetas.
US20080255041A1 (en) * 2007-04-11 2008-10-16 Ebi, L.P. Treatment of annulus fibrosis defects
US8328024B2 (en) 2007-04-12 2012-12-11 Hanuman, Llc Buoy suspension fractionation system
US7806276B2 (en) 2007-04-12 2010-10-05 Hanuman, Llc Buoy suspension fractionation system
EP2259774B1 (en) 2008-02-27 2012-12-12 Biomet Biologics, LLC Methods and compositions for delivering interleukin-1 receptor antagonist
EP2254991B1 (en) 2008-02-29 2018-08-22 Biomet Manufacturing, LLC A system and process for separating a material
US8187475B2 (en) 2009-03-06 2012-05-29 Biomet Biologics, Llc Method and apparatus for producing autologous thrombin
US8313954B2 (en) 2009-04-03 2012-11-20 Biomet Biologics, Llc All-in-one means of separating blood components
IT1394570B1 (it) 2009-07-02 2012-07-05 Fidia Farmaceutici Materiale biologico adatto per la terapia dell osteoartrosi del danno dei legamenti e per il trattamento delle patologie delle articolazioni.
US9011800B2 (en) 2009-07-16 2015-04-21 Biomet Biologics, Llc Method and apparatus for separating biological materials
US8591391B2 (en) 2010-04-12 2013-11-26 Biomet Biologics, Llc Method and apparatus for separating a material
US9555171B2 (en) 2010-09-30 2017-01-31 Depuy Mitek, Llc Methods and devices for collecting separate components of whole blood
US9642956B2 (en) 2012-08-27 2017-05-09 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US10208095B2 (en) 2013-03-15 2019-02-19 Biomet Manufacturing, Llc Methods for making cytokine compositions from tissues using non-centrifugal methods
US9895418B2 (en) 2013-03-15 2018-02-20 Biomet Biologics, Llc Treatment of peripheral vascular disease using protein solutions
US9950035B2 (en) 2013-03-15 2018-04-24 Biomet Biologics, Llc Methods and non-immunogenic compositions for treating inflammatory disorders
US20140271589A1 (en) 2013-03-15 2014-09-18 Biomet Biologics, Llc Treatment of collagen defects using protein solutions
US10143725B2 (en) 2013-03-15 2018-12-04 Biomet Biologics, Llc Treatment of pain using protein solutions
US9550028B2 (en) 2014-05-06 2017-01-24 Biomet Biologics, LLC. Single step desiccating bead-in-syringe concentrating device
US20170369845A1 (en) * 2014-12-31 2017-12-28 Anthrogenesis Corporation Methods for isolation of platelets
US11767511B2 (en) 2018-11-30 2023-09-26 Cellphire, Inc. Platelets as delivery agents
EP3887402A4 (en) 2018-11-30 2022-10-26 Cellphire, Inc. PLATELETS AS RELEASING AGENT
US11529587B2 (en) 2019-05-03 2022-12-20 Cellphire, Inc. Materials and methods for producing blood products
US20210308066A1 (en) 2020-02-04 2021-10-07 Cellphire, Inc. Anti-fibrinolytic loaded platelets
CA3150936A1 (en) 2019-08-16 2021-02-25 Cellphire, Inc. Thrombosomes as an antiplatelet agent reversal agent
US20220273724A1 (en) 2021-02-17 2022-09-01 Cellphire Inc. Freeze-dried platelet derivative compositions for treating antiplatelet induced coagulopathy
CN114831770A (zh) * 2022-05-20 2022-08-02 上海浦灵生物科技有限公司 一种肺动脉高压非人灵长类动物模型及其构建方法

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IT1284550B1 (it) 1996-09-18 1998-05-21 Flavio Tarantino Procedimento per la preparazione di colla di fibrina autologa ad uso chirurgico

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003017913A1 (en) * 2001-08-27 2003-03-06 The Cleveland Clinic Foundation Compositions, methods and apparatus for surgical procedures
WO2004024198A1 (en) * 2002-09-10 2004-03-25 New Dawn-Consultores E Servicos Lda Activator for forming platelet gel, platelet poor plasma gel or platelet rich plasma gel
EP1652538A3 (en) * 2004-10-28 2007-01-31 Medtronic Vascular, Inc. Autologous platelet gel on a stent graft
WO2009121953A3 (en) * 2008-04-04 2010-02-25 Azienda Ospedaliero Universitaria Careggi Extracellular matrix comprising platelet factors
US8691263B2 (en) 2008-04-04 2014-04-08 Azienda Ospedaliero-Universitaria Careggi Extracellular matrix comprising platelet concentrate and cryoprecipitate polymerized in situ
US9199007B2 (en) 2009-06-11 2015-12-01 Banc De Sang I Teixits Use of gelled PRP (platelet gel) for volumetric breast reconstruction
IT201700024672A1 (it) * 2017-03-06 2018-09-06 Caloprisco Gaetano Ditta Individuale Metodo e sistema per preparare un kit medicale per curare lesioni tissutali di un paziente

Also Published As

Publication number Publication date
DE60002231D1 (de) 2003-05-22
EP1239895B1 (en) 2003-04-16
CA2393315C (en) 2010-01-26
WO2001043787A3 (en) 2001-12-13
US20020172666A1 (en) 2002-11-21
AU2511101A (en) 2001-06-25
EP1239895A2 (en) 2002-09-18
ITAL990010U1 (it) 2001-06-14
PT1239895E (pt) 2003-08-29
DE60002231T2 (de) 2004-04-29
JP2003516815A (ja) 2003-05-20
ATE237370T1 (de) 2003-05-15
WO2001043787B1 (en) 2002-01-10
CA2393315A1 (en) 2001-06-21
DK1239895T3 (da) 2003-07-21
ES2197125T3 (es) 2004-01-01
US6841170B2 (en) 2005-01-11

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