EP0790840A1 - Verfahren zur herstellung von calciumoxidarmer spongiosa-knochenkeramik - Google Patents

Verfahren zur herstellung von calciumoxidarmer spongiosa-knochenkeramik

Info

Publication number
EP0790840A1
EP0790840A1 EP95936579A EP95936579A EP0790840A1 EP 0790840 A1 EP0790840 A1 EP 0790840A1 EP 95936579 A EP95936579 A EP 95936579A EP 95936579 A EP95936579 A EP 95936579A EP 0790840 A1 EP0790840 A1 EP 0790840A1
Authority
EP
European Patent Office
Prior art keywords
bone
calcium oxide
ceramics
producing
mineralized
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.)
Withdrawn
Application number
EP95936579A
Other languages
German (de)
English (en)
French (fr)
Inventor
Franz Zorn
Frank Weber
Antonio Almeida
Ilona Taubert
Rolf Wagenknecht
Wilhelm Eberle
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.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
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 Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of EP0790840A1 publication Critical patent/EP0790840A1/de
Withdrawn legal-status Critical Current

Links

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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3683Materials 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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • 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
    • A61K35/32Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
    • 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/12Phosphorus-containing materials, e.g. apatite
    • 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3604Materials 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
    • A61L27/3608Bone, e.g. demineralised bone matrix [DBM], bone powder
    • 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3641Materials 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 site of application in the body
    • A61L27/3645Connective tissue
    • A61L27/365Bones
    • 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • CCHEMISTRY; METALLURGY
    • C04CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04BLIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B35/00Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
    • C04B35/01Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products based on oxide ceramics
    • C04B35/447Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products based on oxide ceramics based on phosphates, e.g. hydroxyapatite
    • CCHEMISTRY; METALLURGY
    • C04CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04BLIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B38/00Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof
    • C04B38/08Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof by adding porous substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00179Ceramics or ceramic-like structures
    • A61F2310/00293Ceramics or ceramic-like structures containing a phosphorus-containing compound, e.g. apatite
    • CCHEMISTRY; METALLURGY
    • C04CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04BLIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B2111/00Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
    • C04B2111/00474Uses not provided for elsewhere in C04B2111/00
    • C04B2111/00836Uses not provided for elsewhere in C04B2111/00 for medical or dental applications

Definitions

  • the invention relates to a process for the production of spongiosa bone ceramic low in calcium oxide.
  • the production of bone ceramics from animal bones usually takes place in such a way that selected bones or pieces of bone are first mechanically freed of all adhering soft tissues, then roughly trimmed by sawing into pieces of suitable shape and size, and then removing all others mineralized organic components.
  • the mineralization process begins with boiling several times in water.
  • the further treatment can take place, for example, with solvents which dissolve fat or protein and / or with the aid of hydrogen peroxide, as described, for example, in EP 0 141 004.
  • Pyrolytic mineralization processes have proven to be particularly simple and effective.
  • the organic portion of the bone is decomposed by the action of heat and the resulting carbon is then burned out in an excess of oxygen. Temperatures between 500 and 1000 ° C are common for bone pyrolysis.
  • cancellous bone material After mineralization The bone is sintered into ceramics, whereby temperatures between 800 and 1400 ° C are common. Sintering gives the material the desired final strength. In the processes mentioned, special care must be taken to ensure that the porous structure of the original bone is preserved as far as possible.
  • the conversion of cancellous bone material to cancellous bone ceramic can preferably be carried out by a method according to DE 3727606, in which special control of the temperature and the reductive or oxidative character of the atmosphere enables particularly gentle pyrolysis.
  • Ceramics come.
  • the proportion of calcium oxide in the bone ceramic is natural and can vary depending on the animal breed and individual husbandry.
  • the calcium oxide arises from the fact that during pyrolysis and sintering the calcium carbonate naturally present in the bone is converted into calcium oxide.
  • the mineralized bone material be subjected to treatment with an aqueous solution of an organic acid, in particular citric acid, before sintering.
  • This step enables calcium oxide to be extracted from the material, so that after sintering, a bone ceramic is obtained which consists of more than 99% X-ray hydroxyapatite by X-ray analysis.
  • this procedure is very effective and leads to a usable stable bone ceramic, there are disadvantages associated with it.
  • the material must first be cooled back to room temperature in order to achieve the
  • the process point has not yet sufficiently solidified and is therefore very sensitive.
  • the present invention was therefore based on the object of alleviating the disadvantages of the previous procedure.
  • the invention thus relates to a process for the production of spongiosa bone ceramics low in calcium oxide, in which cancellous bones prepared in pieces are removed by removing all organic
  • Demineralized water is known as such and is readily available. It can be produced in any amount from natural water by generally known methods, for example by single or multiple distillation and / or removal of the dissolved mineral salts by means of ion exchangers. Demineralized water usually shows a slightly acidic pH, which is around 6.0. It is believed that this slightly acidic nature of the demineralized water favors the leaching of calcium oxide from the mineralized bone matrix.
  • the natural proportion of calcium oxide in the bone is between 5 and 10%.
  • X-ray examination of the ceramic obtained at the end shows that the material consists of more than 95% and generally 97-99% of hydroxyapatite. Calcium oxide can only be detected in traces, if at all.
  • the method according to the invention makes it possible to save not inconsiderable amounts of the acid previously required for a comparable result.
  • rinsing operations to wash the material neutrally are eliminated, so that this can also save costs and time.
  • the method according to the invention is considerably gentler since the hydroxylapatite matrix is not attacked by the treatment with demineralized water.
  • the pieces are dried and then sintered to form the ceramic in the usual way.
  • Raw rod ends of freshly slaughtered cattle, which have been freed from soft tissue, are cut into rectangular pieces measuring roughly 30 x 30 x 100 mm using a saw and boiled with water three times for about 1 hour.
  • the bone pieces are then dried at 110 ° C for 6 hours. Then they are opened under a nitrogen atmosphere within 9 hours
  • the atmosphere is switched linearly to atmospheric oxygen and then heated to 900 ° C within 5 hours.
  • the pieces are placed in a bath of demineralized water (10 1 per 1 kg of bone material) and treated in the moving bath at a temperature of 20 ° C for a period of 48 hours. After this treatment, the pieces are washed 3 times with demineralized water.
  • the pieces are heated to 1250 ° C. within 21 hours, kept at this temperature for 3 hours and then cooled freely.
  • the bone ceramic pieces obtained show the unchanged porous structure of the original cancellous bone.
  • the ceramic consists of about 99% of hydroxyapatite by X-ray.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Transplantation (AREA)
  • Ceramic Engineering (AREA)
  • Botany (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Structural Engineering (AREA)
  • Materials Engineering (AREA)
  • Manufacturing & Machinery (AREA)
  • Developmental Biology & Embryology (AREA)
  • Inorganic Chemistry (AREA)
  • Vascular Medicine (AREA)
  • Rheumatology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Compositions Of Oxide Ceramics (AREA)
EP95936579A 1994-11-10 1995-11-02 Verfahren zur herstellung von calciumoxidarmer spongiosa-knochenkeramik Withdrawn EP0790840A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE4440149 1994-11-10
DE4440149A DE4440149A1 (de) 1994-11-10 1994-11-10 Verfahren zur Herstellung von calciumoxidarmer Spongiosa-Knochenkeramik
PCT/EP1995/004285 WO1996014886A1 (de) 1994-11-10 1995-11-02 Verfahren zur herstellung von calciumoxidarmer spongiosa-knochenkeramik

Publications (1)

Publication Number Publication Date
EP0790840A1 true EP0790840A1 (de) 1997-08-27

Family

ID=6532959

Family Applications (1)

Application Number Title Priority Date Filing Date
EP95936579A Withdrawn EP0790840A1 (de) 1994-11-10 1995-11-02 Verfahren zur herstellung von calciumoxidarmer spongiosa-knochenkeramik

Country Status (11)

Country Link
US (1) US5776843A (xx)
EP (1) EP0790840A1 (xx)
JP (1) JPH10508572A (xx)
AU (1) AU696250B2 (xx)
CZ (1) CZ142997A3 (xx)
DE (1) DE4440149A1 (xx)
HU (1) HUT77186A (xx)
PL (1) PL320083A1 (xx)
SK (1) SK58697A3 (xx)
WO (1) WO1996014886A1 (xx)
ZA (1) ZA959568B (xx)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102173278A (zh) * 2011-01-24 2011-09-07 邱林铿 一种在强化牙瓷上装饰骨瓷装饰配件的陶瓷制品及其制作方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3727606A1 (de) * 1987-08-19 1989-05-03 Aesculap Ag Verfahren zur herstellung eines knochenersatzmaterials
JPH0251481A (ja) * 1988-02-01 1990-02-21 Asahi Optical Co Ltd 多孔質アパタイト焼結体の製法
DE3903695A1 (de) * 1989-02-08 1990-08-09 Merck Patent Gmbh Resorbierbare knochenkeramik auf basis von tricalciumphosphat
US5236456A (en) * 1989-11-09 1993-08-17 Osteotech, Inc. Osteogenic composition and implant containing same
DE4028683A1 (de) * 1990-09-10 1992-03-12 Merck Patent Gmbh Implantatmaterial
JPH04198007A (ja) * 1990-11-28 1992-07-17 Kanebo Ltd ヒドロキシアパタイト及びその製造方法
SE9303977L (sv) * 1993-11-30 1995-01-09 Corimed Gmbh Förfarande för framställning av keramiskt implantatmaterial, företrädesvis hydroxylapatit uppvisande keramiskt implantatmaterial

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9614886A1 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102173278A (zh) * 2011-01-24 2011-09-07 邱林铿 一种在强化牙瓷上装饰骨瓷装饰配件的陶瓷制品及其制作方法
CN102173278B (zh) * 2011-01-24 2013-09-25 邱林铿 一种在强化牙瓷上装饰骨瓷装饰配件的陶瓷制品及其制作方法

Also Published As

Publication number Publication date
PL320083A1 (en) 1997-09-15
AU3846095A (en) 1996-06-06
CZ142997A3 (en) 1997-09-17
JPH10508572A (ja) 1998-08-25
SK58697A3 (en) 1997-10-08
ZA959568B (en) 1996-07-23
WO1996014886A1 (de) 1996-05-23
HUT77186A (hu) 1998-03-02
MX9703291A (es) 1998-05-31
AU696250B2 (en) 1998-09-03
US5776843A (en) 1998-07-07
DE4440149A1 (de) 1996-05-15

Similar Documents

Publication Publication Date Title
EP0475189B1 (de) Implantatmaterial
EP0657178B1 (de) Verfahren zur Herstellung von Implantatkeramikmaterial, insbesonders von Hydroxylapatit aufweisenden Implantatkeramikmaterial
EP0141004B1 (de) Knochenersatzmaterial auf der Basis natürlicher Knochen
DE69111021T2 (de) Flexible Membrane hergestellt aus organischer Knochenmatrix zum Ausbessern und Wiederherstellen von Knochen.
DE3542744C1 (de) Poroeses Hydroxylapatit-Material
DE2917135C2 (de) Verfahren zum Herstellen von Transplantaten
DE3617896A1 (de) Knochenpfropfmaterial und verfahren zu seiner herstellung
EP0012959B1 (de) Verfahren zur Herstellung von Knochenersatzmaterial mit verbesserter biologischer Stabilität auf der Basis von Kollagen und das erhaltene Knochenersatzmaterial
DE3617897A1 (de) Verfahren zur herstellung von prothesen als ersatz fuer gelenkknorpel und die so hergestellten prothesen
DE3709897A1 (de) Verfahren zur herstellung eines hydroxylapatitmaterials
DE69422387T2 (de) Zur verwendung in medizin und chirurgie geeignetes halbsynthetisches material
EP0383773B1 (de) Verfahren zur herstellung eines knochenersatzmaterials
EP0727231B1 (de) Verfahren zur Herstellung von Spongiosa-Knochenkeramikformkörpern
EP0364871A1 (de) Verfahren zur Herstellung von Rinder-Pericard-Materialien und ihre Verwendung
DE2840064C2 (de) Verfahren zur Herstellung von Knochenkontaktschichten
EP1124593B1 (de) Verfahren zur präparation von knochenmaterial
EP0790840A1 (de) Verfahren zur herstellung von calciumoxidarmer spongiosa-knochenkeramik
DE60021412T2 (de) Biokompatibles Gewebe für Sehnen oder Ligamente sowie ein Herstellungsverfahren dafür
EP3777904B1 (de) Osteotroper knochenersatz
CN1162924A (zh) 制备具有低氧化钙含量的海绵骨瓷的方法
EP0012443A1 (de) Zahnpulpahöhlenfüllmaterial, bestehend aus Kollagen und Verfahren zu dessen Herstellung
Willebrand et al. 273. Der biologische Wert des corticospongiösen Eigenspanes gegenüber dem Fremdspan beim Knochenersatz am Handskelet
MXPA97003291A (en) Process for the production of spongeous bone ceramics that has low oxid content of cal
DE8534024U1 (de) Poröses Knochenersatz-Implantat

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19970426

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU NL PT SE

AX Request for extension of the european patent

Free format text: LT PAYMENT 970426;SI PAYMENT 970426

17Q First examination report despatched

Effective date: 20000918

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20020701