JP5805791B2 - ゲル化性コラーゲン及びその供給手段 - Google Patents
ゲル化性コラーゲン及びその供給手段 Download PDFInfo
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- JP5805791B2 JP5805791B2 JP2013552871A JP2013552871A JP5805791B2 JP 5805791 B2 JP5805791 B2 JP 5805791B2 JP 2013552871 A JP2013552871 A JP 2013552871A JP 2013552871 A JP2013552871 A JP 2013552871A JP 5805791 B2 JP5805791 B2 JP 5805791B2
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- 102000008186 Collagen Human genes 0.000 title claims description 118
- 108010035532 Collagen Proteins 0.000 title claims description 118
- 229920001436 collagen Polymers 0.000 title claims description 118
- 239000000243 solution Substances 0.000 claims description 57
- 239000000203 mixture Substances 0.000 claims description 43
- 239000007853 buffer solution Substances 0.000 claims description 32
- 210000000845 cartilage Anatomy 0.000 claims description 29
- 230000007547 defect Effects 0.000 claims description 23
- 238000002156 mixing Methods 0.000 claims description 23
- 239000007788 liquid Substances 0.000 claims description 18
- 210000001519 tissue Anatomy 0.000 claims description 10
- 229940071643 prefilled syringe Drugs 0.000 claims description 8
- 238000001356 surgical procedure Methods 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 5
- 230000003472 neutralizing effect Effects 0.000 claims description 5
- 210000002435 tendon Anatomy 0.000 claims description 5
- 230000003068 static effect Effects 0.000 claims description 4
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 238000002316 cosmetic surgery Methods 0.000 claims description 2
- 210000004872 soft tissue Anatomy 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims 1
- 238000000034 method Methods 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000007943 implant Substances 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 9
- 239000000499 gel Substances 0.000 description 8
- 239000000872 buffer Substances 0.000 description 6
- 230000001143 conditioned effect Effects 0.000 description 6
- 239000000654 additive Substances 0.000 description 5
- 210000001612 chondrocyte Anatomy 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000512 collagen gel Substances 0.000 description 3
- 238000004925 denaturation Methods 0.000 description 3
- 230000036425 denaturation Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 210000001188 articular cartilage Anatomy 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000000501 collagen implant Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000001879 gelation Methods 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 229960001438 immunostimulant agent Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 206010061762 Chondropathy Diseases 0.000 description 1
- 206010050296 Intervertebral disc protrusion Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 208000035965 Postoperative Complications Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 210000003321 cartilage cell Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000002648 chondrogenic effect Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000003035 hyaline cartilage Anatomy 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000012977 invasive surgical procedure Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 238000002324 minimally invasive surgery Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000000518 rheometry Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005496 tempering Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- 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
- A61L27/52—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/24—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic
- A61M5/2448—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic comprising means for injection of two or more media, e.g. by mixing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Dispersion Chemistry (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Vascular Medicine (AREA)
- Anesthesiology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Prostheses (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
濃縮コラーゲン溶液を製造するために、ラット尾を約マイナス20℃で保管し、続いて数分間約70%のアルコール中で表面的に消毒する。皮膚を引きはがし、個々のコラーゲン繊維を分離する。コラーゲン繊維をもう一度アルコール中で表面的に消毒してからPBSで洗浄し、続いて約0.1%の(0.5mol/l)酢酸溶液に移してその中でインキュベートする。コラーゲン繊維を酢酸溶液中で少なくとも7日間、冷温で(約0〜4℃において)撹拌する。不溶性のコラーゲン部分をインキュベーション時間の終了時に分離してから、コラーゲンをろ過し、沈殿させる。沈殿物(Prazipitor)を緩衝溶液ですすぎ、凍結してから、凍結乾燥する。凍結乾燥したコラーゲンを0.1%酢酸中に所定通り吸着させ、9〜16mg/mlのコラーゲン含有量を得る。濃縮コラーゲン溶液のpH値は、約4.0である。
例1に基づき製造可能なコラーゲン組成物をレオロジー検査する。ダブルチャンバーシリンジ(例えば、Medmix Systems社、スイス)内に、コラーゲン溶液(10mg/ml)及び緩衝溶液を、例1に基づき充填し(コラーゲンチャンバー:4部のコラーゲン溶液、2ml;緩衝液チャンバー:1部の五倍濃縮緩衝液、0.5ml)、凍結する。
Claims (5)
- 人体又は動物体の関節又は器官における軟骨欠損を予防的又は治療的に処置するための充填済みシリンジであって、それにより、液体ゲル化性コラーゲン組成物が、軟骨欠損の空洞に投与され、該充填済みシリンジは、シリンジに結合した混合装置内で合流する少なくとも二つの別々のチャンバーを含み、各チャンバーの内容物を前記混合装置を通して同時に放出でき、少なくとも一つの第一のチャンバーが、8mg/ml超のコラーゲン含有量を有し、pH値が(21℃に関して)6以下である液体コラーゲン溶液で充填されており、少なくとも一つのそれとは別の第二のチャンバーが、中和性の緩衝溶液で充填されていることを特徴とする、充填済みシリンジ。
- 液体ゲル化性コラーゲン組成物の投与による、椎間板ヘルニア後に起こる髄核中の組織喪失の治療のための、皮膚軟部組織欠損の治療のための、骨欠損及び腱欠損の治療のための、歯肉欠損の再建のための、歯科学及び顎顔面外科における別の用途のための、並びに形成外科での用途のための充填済みシリンジであって、該充填済みシリンジは、シリンジに結合した混合装置内で合流する少なくとも二つの別々のチャンバーを含み、各チャンバーの内容物を前記混合装置を通して同時に放出でき、少なくとも一つの第一のチャンバーが、8mg/ml超のコラーゲン含有量を有し、pH値が(21℃に関して)6以下である液体コラーゲン溶液で充填されており、少なくとも一つのそれとは別の第二のチャンバーが、中和性の緩衝溶液で充填されていることを特徴とする、充填済みシリンジ。
- 混合装置が静的ミキサーである、請求項1又は2に記載のシリンジ。
- 製造されるコラーゲン組成物が、6mg/ml以上のコラーゲン含有量を有する、請求項1〜3のいずれか一項に記載のシリンジ。
- 前記コラーゲン溶液が、10 1 〜10 5 mPa・sの動的粘度を有する、請求項1〜4のいずれか一項に記載のシリンジ。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102011011092A DE102011011092A1 (de) | 2011-02-09 | 2011-02-09 | Gelierendes Kollagen und Mittel zu dessen Bereitstellung |
DE102011011092.5 | 2011-02-09 | ||
PCT/EP2012/000336 WO2012107174A1 (de) | 2011-02-09 | 2012-01-26 | Gelierendes kollagen und mittel zu dessen bereitstellung |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2014509229A JP2014509229A (ja) | 2014-04-17 |
JP5805791B2 true JP5805791B2 (ja) | 2015-11-10 |
Family
ID=45592308
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013552871A Active JP5805791B2 (ja) | 2011-02-09 | 2012-01-26 | ゲル化性コラーゲン及びその供給手段 |
Country Status (13)
Country | Link |
---|---|
US (1) | US20130324473A1 (ja) |
EP (1) | EP2673013B1 (ja) |
JP (1) | JP5805791B2 (ja) |
AU (1) | AU2012216199B2 (ja) |
BR (1) | BR112013020359B8 (ja) |
CA (1) | CA2826628C (ja) |
CL (1) | CL2013002332A1 (ja) |
CY (1) | CY1118912T1 (ja) |
DE (1) | DE102011011092A1 (ja) |
ES (1) | ES2626206T3 (ja) |
PT (1) | PT2673013T (ja) |
RU (1) | RU2613716C2 (ja) |
WO (1) | WO2012107174A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102012213496A1 (de) * | 2012-07-31 | 2014-05-15 | Amedrix Gmbh | Kit, dessen Verwendung und Verfahren zum Auffüllen von Bindegewebe der Haut |
EP3076902A4 (en) * | 2013-12-03 | 2017-08-16 | Cornell University | Method of repairing an annulus and collagen gel composition |
DE102015000363A1 (de) | 2015-01-20 | 2016-07-21 | Emc Microcollections Gmbh | Neue modular funktionalisierbare Peptid-Hydrogele |
EP3666298A1 (en) * | 2018-12-13 | 2020-06-17 | Global Stem Cell Technology | A collagen formulation suitable for injection |
RU2764514C1 (ru) * | 2020-12-23 | 2022-01-18 | федеральное государственное бюджетное образовательное учреждение высшего образования "Северный государственный медицинский университет" Министерства здравоохранения Российской Федерации | Способ выделения коллагеновых волокон дермы |
CN116999619B (zh) * | 2023-08-03 | 2024-03-19 | 浙江崇山生物制品有限公司 | 一种软骨用胶原凝胶及其制备方法 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3968567A (en) * | 1975-04-21 | 1976-07-13 | Nevins Alan J | Endodontic composition and method |
DE60016775D1 (de) * | 1999-10-05 | 2005-01-20 | Transkaryotic Therapies Inc | Hybride matrizen und gemische davon |
WO2001066472A1 (en) * | 2000-03-06 | 2001-09-13 | Tei Biosciences, Inc. | Injectable bio-compatible material and methods of use |
DE20019809U1 (de) | 2000-05-31 | 2001-07-12 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V., 80636 München | Knorpelersatz und Biomatrix zur Kultivierung von Zellen |
US20030211793A1 (en) * | 2001-03-05 | 2003-11-13 | Eugene Bell | Injectable bio-compatible material and methods of use |
DE102005034420A1 (de) * | 2004-12-23 | 2006-07-06 | Ossacur Ag | Gelartiges Material zur Füllung von Knochen- und/oder Knorpeldefekten |
DE102006026591B4 (de) * | 2006-05-31 | 2008-09-04 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Verfahren zur Isolierung von Kollagen aus kollagenhaltigem Gewebe |
JP2010509943A (ja) * | 2006-09-28 | 2010-04-02 | チルドレンズ メディカル センター コーポレーション | 組織を修復する方法およびそのためのコラーゲン生成物 |
WO2011126294A2 (ko) * | 2010-04-06 | 2011-10-13 | 동국대학교 산학협력단 | 콜라겐 하이드로겔 제조용 멀티 시린지 |
-
2011
- 2011-02-09 DE DE102011011092A patent/DE102011011092A1/de not_active Ceased
-
2012
- 2012-01-26 BR BR112013020359A patent/BR112013020359B8/pt active IP Right Grant
- 2012-01-26 EP EP12703688.7A patent/EP2673013B1/de active Active
- 2012-01-26 WO PCT/EP2012/000336 patent/WO2012107174A1/de active Application Filing
- 2012-01-26 JP JP2013552871A patent/JP5805791B2/ja active Active
- 2012-01-26 ES ES12703688.7T patent/ES2626206T3/es active Active
- 2012-01-26 AU AU2012216199A patent/AU2012216199B2/en active Active
- 2012-01-26 US US13/984,462 patent/US20130324473A1/en not_active Abandoned
- 2012-01-26 PT PT127036887T patent/PT2673013T/pt unknown
- 2012-01-26 CA CA2826628A patent/CA2826628C/en active Active
- 2012-01-26 RU RU2013141169A patent/RU2613716C2/ru active
-
2013
- 2013-08-09 CL CL2013002332A patent/CL2013002332A1/es unknown
-
2017
- 2017-05-30 CY CY20171100557T patent/CY1118912T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
US20130324473A1 (en) | 2013-12-05 |
BR112013020359B1 (pt) | 2019-09-10 |
CA2826628C (en) | 2016-01-19 |
JP2014509229A (ja) | 2014-04-17 |
BR112013020359A2 (pt) | 2016-10-18 |
CL2013002332A1 (es) | 2014-03-07 |
PT2673013T (pt) | 2017-06-14 |
AU2012216199B2 (en) | 2015-12-03 |
RU2613716C2 (ru) | 2017-03-21 |
DE102011011092A1 (de) | 2012-08-23 |
CA2826628A1 (en) | 2012-08-16 |
RU2013141169A (ru) | 2015-03-20 |
WO2012107174A1 (de) | 2012-08-16 |
EP2673013B1 (de) | 2017-03-15 |
EP2673013A1 (de) | 2013-12-18 |
BR112013020359B8 (pt) | 2022-01-25 |
ES2626206T3 (es) | 2017-07-24 |
AU2012216199A1 (en) | 2013-08-29 |
CY1118912T1 (el) | 2018-01-10 |
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