JP5385532B2 - 脊柱癒着の防止において使用される、硫酸化ヒアルロン酸とゲランとからなるバイオマテリアル - Google Patents
脊柱癒着の防止において使用される、硫酸化ヒアルロン酸とゲランとからなるバイオマテリアル Download PDFInfo
- Publication number
- JP5385532B2 JP5385532B2 JP2007535074A JP2007535074A JP5385532B2 JP 5385532 B2 JP5385532 B2 JP 5385532B2 JP 2007535074 A JP2007535074 A JP 2007535074A JP 2007535074 A JP2007535074 A JP 2007535074A JP 5385532 B2 JP5385532 B2 JP 5385532B2
- Authority
- JP
- Japan
- Prior art keywords
- hyaluronic acid
- sulfated hyaluronic
- sulfated
- gellan
- biomaterial
- 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.)
- Expired - Lifetime
Links
Images
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
- A61L31/04—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/795—Polymers containing sulfur
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61L31/041—Mixtures of macromolecular compounds
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITPD2004A000245 | 2004-10-08 | ||
| IT000245A ITPD20040245A1 (it) | 2004-10-08 | 2004-10-08 | Biomateriali costituiti da acido ialuronico solfatato e gellano utilizzabili nella prevenzione delle adesioni spinali |
| PCT/EP2005/010645 WO2006037592A1 (en) | 2004-10-08 | 2005-10-03 | Biomaterials consisting of sulphated hyaluronic acid and gellan to be used in the prevention of spinal adhesions |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008515832A JP2008515832A (ja) | 2008-05-15 |
| JP2008515832A5 JP2008515832A5 (enExample) | 2008-11-20 |
| JP5385532B2 true JP5385532B2 (ja) | 2014-01-08 |
Family
ID=35610035
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007535074A Expired - Lifetime JP5385532B2 (ja) | 2004-10-08 | 2005-10-03 | 脊柱癒着の防止において使用される、硫酸化ヒアルロン酸とゲランとからなるバイオマテリアル |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US8563039B2 (enExample) |
| EP (1) | EP1796752B1 (enExample) |
| JP (1) | JP5385532B2 (enExample) |
| KR (1) | KR20070107658A (enExample) |
| CN (1) | CN101035575B (enExample) |
| AU (1) | AU2005291474B2 (enExample) |
| BR (1) | BRPI0516568A (enExample) |
| CA (1) | CA2583149C (enExample) |
| IT (1) | ITPD20040245A1 (enExample) |
| MX (1) | MX2007004158A (enExample) |
| RU (1) | RU2383336C2 (enExample) |
| WO (1) | WO2006037592A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITPD20050206A1 (it) * | 2005-07-07 | 2007-01-08 | Fidia Advanced Biopolymers Srl | Biomateriali in forma di fibra da impiegarsi come dispositivi medici nel trattamento delle ferite e loro processi di produzione |
| JP5088864B2 (ja) * | 2007-03-16 | 2012-12-05 | オリンパス株式会社 | 生体組織補填材とその製造方法 |
| CA2719666C (en) | 2008-04-04 | 2016-08-16 | Glenn Prestwich | Alkylated semi-synthetic glycosaminoglycosan ethers, and methods for making and using thereof |
| US8343942B2 (en) | 2008-04-04 | 2013-01-01 | University Of Utah Research Foundation | Methods for treating interstitial cystitis |
| EP2280739B1 (en) * | 2008-06-03 | 2012-07-04 | Actamax Surgical Materials LLC | A tissue coating for preventing undesired tissue-to-tissue adhesions |
| EP2387390B1 (en) | 2009-01-13 | 2012-11-28 | PharmaSurgics in Sweden AB | Hylauronic acid containing compositions for treatment of wounds, scars, post-surgical adhesion formation |
| IT1397247B1 (it) * | 2009-05-14 | 2013-01-04 | Fidia Farmaceutici | Nuovi agenti regolatori dell'attivita' citochinica |
| EP2688402B1 (en) | 2011-03-23 | 2018-10-24 | University of Utah Research Foundation | Means for treating or preventing urological inflammation |
| ITMI20120664A1 (it) | 2012-04-20 | 2013-10-21 | Anika Therapeutics Srl | Biomateriali a base di gellano per l'uso come filler in chirurgia |
| ITMI20130221A1 (it) * | 2013-02-18 | 2014-08-19 | Novagenit S R L | Formulazione a base di polisaccaridi biocompatibili e biodegradabili da impiegare in chirurgia |
| US11337994B2 (en) | 2016-09-15 | 2022-05-24 | University Of Utah Research Foundation | In situ gelling compositions for the treatment or prevention of inflammation and tissue damage |
| US10590257B2 (en) | 2016-09-26 | 2020-03-17 | The Board Of Trustees Of The Leland Stanford Junior University | Biomimetic, moldable, self-assembled cellulose silica-based trimeric hydrogels and their use as viscosity modifying carriers in industrial applications |
| US11969526B2 (en) | 2017-04-03 | 2024-04-30 | The Board Of Trustees Of The Leland Stanford Junior University | Adhesion prevention with shear-thinning polymeric hydrogels |
| US11975123B2 (en) | 2018-04-02 | 2024-05-07 | The Board Of Trustees Of The Leland Stanford Junior University | Adhesion prevention with shear-thinning polymeric hydrogels |
| WO2020072495A1 (en) | 2018-10-01 | 2020-04-09 | The Board Of Trustees Of The Leland Stanford Junior University | Injectable hydrogels for controlled release of immunomodulatory compounds |
| CN111228653A (zh) | 2018-11-13 | 2020-06-05 | 格莱科米拉治疗公司 | 用电离辐射加强癌症治疗的方法 |
| RU2744752C1 (ru) * | 2020-08-28 | 2021-03-15 | Федеральное государственное бюджетное учреждение науки Институт проблем химико-энергетических технологий Сибирского отделения Российской академии наук (ИПХЭТ СО РАН) | Способ получения противоспаечного материала |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4326053A (en) * | 1978-12-04 | 1982-04-20 | Merck & Co., Inc. | Polysaccharide S-60 and bacterial fermentation process for its preparation |
| US5080893A (en) * | 1988-05-31 | 1992-01-14 | University Of Florida | Method for preventing surgical adhesions using a dilute solution of polymer |
| IT1254704B (it) * | 1991-12-18 | 1995-10-09 | Mini Ricerca Scient Tecnolog | Tessuto non tessuto essenzialmente costituito da derivati dell'acido ialuronico |
| ITPD940054A1 (it) * | 1994-03-23 | 1995-09-23 | Fidia Advanced Biopolymers Srl | Polisaccaridi solfatati |
| CN1301139C (zh) * | 1995-08-29 | 2007-02-21 | 菲迪亚高级生物聚合物公司 | 包括透明质酸衍生物的用于预防手术后粘连的生物材料 |
| SE9603480L (sv) * | 1996-09-23 | 1998-03-24 | Johan Carlfors | Beredningsform för svårlösliga läkemedel |
| AU738788B2 (en) * | 1997-04-04 | 2001-09-27 | Fidia Farmaceutici S.P.A. | N-sulphated hyaluronic acid compounds, derivatives thereof and a process for their preparation |
| IT1294797B1 (it) * | 1997-07-28 | 1999-04-15 | Fidia Advanced Biopolymers Srl | Uso dei derivati dell'acido ialuronico nella preparazione di biomateriali aventi attivita' emostatica fisica e tamponante |
| GB0015682D0 (en) * | 2000-06-28 | 2000-08-16 | Bristol Myers Squibb Co | Sprayable wound care composition |
| IT1317359B1 (it) * | 2000-08-31 | 2003-06-16 | Fidia Advanced Biopolymers Srl | Polisaccaridi percarbossilati, quali l'acido ialuronico, processo perla loro preparazione e loro impiego in campo farmaceutico e |
| US20030219431A1 (en) * | 2002-05-24 | 2003-11-27 | Empire Pharmaceuticals, Inc. | Treatment of neuronal and neurological damage associated with spinal cord injury |
-
2004
- 2004-10-08 IT IT000245A patent/ITPD20040245A1/it unknown
-
2005
- 2005-10-03 CN CN2005800340303A patent/CN101035575B/zh not_active Expired - Lifetime
- 2005-10-03 EP EP05800102A patent/EP1796752B1/en not_active Expired - Lifetime
- 2005-10-03 WO PCT/EP2005/010645 patent/WO2006037592A1/en not_active Ceased
- 2005-10-03 BR BRPI0516568-7A patent/BRPI0516568A/pt not_active IP Right Cessation
- 2005-10-03 RU RU2007112777/15A patent/RU2383336C2/ru not_active IP Right Cessation
- 2005-10-03 CA CA2583149A patent/CA2583149C/en not_active Expired - Lifetime
- 2005-10-03 AU AU2005291474A patent/AU2005291474B2/en not_active Expired
- 2005-10-03 MX MX2007004158A patent/MX2007004158A/es unknown
- 2005-10-03 JP JP2007535074A patent/JP5385532B2/ja not_active Expired - Lifetime
- 2005-10-03 KR KR1020077007821A patent/KR20070107658A/ko not_active Withdrawn
- 2005-10-03 US US11/664,754 patent/US8563039B2/en active Active
-
2012
- 2012-05-10 US US13/468,405 patent/US8728524B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0516568A (pt) | 2008-09-09 |
| AU2005291474B2 (en) | 2011-06-02 |
| RU2007112777A (ru) | 2008-10-10 |
| RU2383336C2 (ru) | 2010-03-10 |
| ITPD20040245A1 (it) | 2005-01-08 |
| CN101035575A (zh) | 2007-09-12 |
| CA2583149C (en) | 2013-09-10 |
| EP1796752B1 (en) | 2012-12-12 |
| US20090202639A1 (en) | 2009-08-13 |
| US20130184234A1 (en) | 2013-07-18 |
| EP1796752A1 (en) | 2007-06-20 |
| CA2583149A1 (en) | 2006-04-13 |
| KR20070107658A (ko) | 2007-11-07 |
| AU2005291474A1 (en) | 2006-04-13 |
| JP2008515832A (ja) | 2008-05-15 |
| MX2007004158A (es) | 2007-10-08 |
| WO2006037592A1 (en) | 2006-04-13 |
| CN101035575B (zh) | 2011-12-14 |
| US8563039B2 (en) | 2013-10-22 |
| US8728524B2 (en) | 2014-05-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8728524B2 (en) | Biomaterials consisting of sulphated hyaluronic acid and gellan to be used in the prevention of spinal adhesions | |
| Gilarska et al. | Collagen/chitosan/hyaluronic acid–based injectable hydrogels for tissue engineering applications–design, physicochemical and biological characterization | |
| JP5746617B2 (ja) | キトサン混合物を形成する注入可能なヒドロゲル | |
| Rodríguez-Vázquez et al. | Chitosan and its potential use as a scaffold for tissue engineering in regenerative medicine | |
| Mao et al. | A preliminary study on chitosan and gelatin polyelectrolyte complex cytocompatibility by cell cycle and apoptosis analysis | |
| KR100674177B1 (ko) | 교차 결합된 히알루론산과 그것의 의학적 용도 | |
| Chang et al. | Citric acid crosslinked sphingan WL gum hydrogel films supported ciprofloxacin for potential wound dressing application | |
| Li et al. | Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention | |
| Wei et al. | Injectable hydrogel based on dodecyl-modified N-carboxyethyl chitosan/oxidized konjac glucomannan effectively prevents bleeding and postoperative adhesions after partial hepatectomy | |
| Wei et al. | A thermosensitive chitosan-based hydrogel barrier for post-operative adhesions' prevention | |
| Kaczmarek-Pawelska | Alginate-based hydrogels in regenerative medicine | |
| Cai et al. | Physically cross-linked hyaluronan-based ultrasoft cryogel prepared by freeze–thaw technique as a barrier for prevention of postoperative adhesions | |
| Huang et al. | Thermosensitive hydrogels based on methylcellulose derivatives for prevention of postoperative adhesion | |
| AU708758B2 (en) | Anti-adhesion agent | |
| Rezakhani et al. | Recent advances in hydrogels applications for tissue engineering and clinical trials | |
| US6486140B2 (en) | Agents, and methods employing them, for the prevention or reduction of tissue adhesion at a wound site | |
| CN110038161A (zh) | 一种新型透明质酸流动凝胶及其制备方法和应用 | |
| JP2004181121A (ja) | 軟骨組織再生用注入剤組成物 | |
| Sudha et al. | Advances in guar gum-based materials in biomedical applications with special reference to tissue engineering applications | |
| Prasannavenkadesan et al. | 4 Chitosan in orthopedics: current advancements and future prospects | |
| HK1107031A (en) | Biomaterials consisting of sulphated hyaluronic acid and gellan to be used in the prevention of spinal adhesions | |
| Dik et al. | Polymer-based anti-adhesive barriers: A comprehensive overview of current approaches for medical and biological applications | |
| Shalaby et al. | Hyaluronic Acid-Based Systems |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080930 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080930 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111025 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120118 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120125 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120223 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120605 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120823 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120830 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120925 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120926 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121002 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121003 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121204 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130402 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130801 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20130813 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130924 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131004 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5385532 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |