JP2009506011A - 慢性炎症性腸疾患の患者における鉄欠乏状態の経口処置用の薬剤を調製するための鉄(iii)複合化合物 - Google Patents
慢性炎症性腸疾患の患者における鉄欠乏状態の経口処置用の薬剤を調製するための鉄(iii)複合化合物 Download PDFInfo
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- JP2009506011A JP2009506011A JP2008527459A JP2008527459A JP2009506011A JP 2009506011 A JP2009506011 A JP 2009506011A JP 2008527459 A JP2008527459 A JP 2008527459A JP 2008527459 A JP2008527459 A JP 2008527459A JP 2009506011 A JP2009506011 A JP 2009506011A
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Abstract
【解決手段】 慢性炎症性腸疾患、特にクローン病および潰瘍性大腸炎の患者における鉄欠乏状態の経口処置用薬剤を調製するための、炭水化物およびそれらの誘導体との鉄(III)複合化合物の使用が開示される
【選択図】図1
Description
患者
慢性炎症性腸疾患(活動性状態または休止状態にある潰瘍性大腸炎またはクローン病)および鉄欠乏症(平均赤血球容量(MCV)<80fL、s−フェリチン<15μg/l、またはs−可溶性トランスフェリンレセプター>1.54mg/lで規定)に罹患している41人の患者を、ランダム化理論に従って、2つのグループに分けた。研究が実施される前の6週間に鉄療法または輸血を受けた患者、研究開始前の2月未満に開始されたアザチオプリン処置、またはインフリキシマブ処置を受けた患者、コバラミン欠乏症または葉酸欠乏症、ガンまたは腎臓疾患に罹患している患者、または妊娠している患者は除外した。血液、尿および便の分析、ならびに疾患の臨床評価を1〜15日で行った。
グループ1において、硫酸鉄(II)(Nycoplus Ferro−Retard、Nycomed Pharma AS、ノルウェー)を、朝に1錠(100mg、100mgFe2+に相当)、食間の夕方に1錠(100mg)投与する処置を14日間実行した。グループ2においては、鉄(III)−ポリマルトース複合体(Maltofer Filmtabletten(Vifor International AG、スイス))を、日に1回、朝食の間に2錠(全部で200mg、200mgFe(III)に相当)投与する処置を14日間実行した。製薬会社の推奨するものに従って錠剤を摂取させた。配った錠剤の消費量によって、患者のコンプライアンスを規定した。80%の患者が満足しているとみなした。
夜から何も食べていない状態で朝に、血液サンプルを採取した。
血中赤血球沈降率(B−ESR)の測定;ならびに血清タンパク質および血清アルブミンの量の決定。
鉄療法の前(1日目)および後(15日目)に臨床疾患の状態を記録した。クローン病患者における臨床疾患活動性を、Harvey−Bradshaw簡易指数(Simple Index)(非特許文献17)により評価した。Harvey−Bradshaw簡易指数(Simple Index)は、次の5つのパラメータに基づいている:一般的な健康状態、腹痛、排便頻度、腹部腫瘤および腸管外合併症。この指数の最大値は25点であり、≧5点であれば、活動状態にあるクローン病であることを示している。
研究の第一の目的は、酸化組織ダメージのためのマーカーに対する経口用硫酸鉄(II)および経口用鉄(III)−ポリマルトース複合体の作用の比較であった。第一の結果は、プラズマMDAおよび尿イソ−PGF2αであった。第二の目的は、臨床疾患活動性および特定の症状に対する2つの鉄製剤の作用の比較であった。処置時間は、鉄欠乏の解消に対する臨床的効果の研究のためには短すぎた。
2つのグループ間の差を、対応のあるスチューデントt検定および対応のないスチューデントt検定を使って評価した。その差の平均および95%信頼区間を記録した。ウィルコクソン検定を使って、その値を一対の差に対して分析した。そして、メディアン値および範囲を記録した。比の比較をフィッシャーの正確確率検定で評価した。0.05未満のp値は、統計的に有意であると考えられる。ウィンドウズ(登録商標)統計ソフトウェアパッケージ用のGraphPad Prism4(GraphPadソフトウェア社、サンディエゴ、米国)を使って、データを分析した。
41人の患者(表1)を、硫酸鉄(II)(n=21)または鉄(III)−ポリマルトース複合体(n=20)のいずれかの処置のために、ランダム化理論に従って分けた。プロトコルに従って、37人の患者の研究を完了させた。これらの患者においては、錠剤を数えることで、硫酸鉄(II)(100%(82〜100))および鉄(III)−ポリマルトース複合体(100%(86〜100))による処置を受けている患者における比較可能なコンプライアンスが得られた。3人の患者(クローン病1人、潰瘍性大腸炎2人)は、それぞれ1日後、4日後および5日後に硫酸鉄(II)の摂取を中止した。1人の患者(クローン病)は、1日後に鉄(III)−ポリマルトース複合体による処置を中止した。彼ら全てが、激しい排便、腹痛および嘔吐に見舞われた。これらの患者は、実験室数値の分析から除外したが、臨床疾患活動度および症状点数の分析には含めた。
硫酸鉄(II)による処置は、血漿MDA値を95nmol/l(CI 18〜171;p=0.018)にまで明らかに引き上げ(図1)、尿イソ−PGF2α値を194pg/mgクレアチニン(CI 58〜447;p=0.12)にまで増加させた。鉄(III)−ポリマルトース複合体による処置では、血漿MDA値(p=0.16)(図1)または尿イソ−PGF2α値(p=0.56)(表2)は、あまり変化しなかった。血漿中のビタミンA、CおよびE、β−カロチン、グルタチオン、システイン、システイニルグリシンおよびホモシステインは、両方の処置の後においても変化がなかった(表2)。硫酸鉄(II)と鉄(III)−ポリマルトース複合体との比較に関しては、血漿MDA値(p=0.08)または尿イソ−PGF2α値(p=0.28)の変化(処置前−処置後)は、あまり異ならなかった。しかしながら、2つのグループの平均血漿MDA値は、特定の処置の後で顕著に異なっており(p=0.007)、より高いMDA値が硫酸鉄(II)グループに見られた(表2)。尿および血漿のパラメータのいずれもが、疾患活動性指数とは相関しなかった。
臨床疾患活動性の点数は、表3に示される。硫酸鉄(II)(p=0.45)による処置または鉄(III)−ポリマルトース複合体(p=0.80)による処置のいずれにおいても、臨床疾患活動性指数は、実質的に変化しなかった。その変化は、処置間で異ならなかった(p=0.81)。硫酸鉄(II)による処置の間、排便の回数が増加した(19(7−106)〜24(7−55);p=0.0087)。一方、鉄(III)−ポリマルトース複合体では、1週間あたりの排便の回数合計は変化しなかった(17(7−46)〜17(6−66);p=0.25)。硫酸鉄(II)または鉄(III)−ポリマルトース複合体のいずれもが、健康状態点数または腹痛点数に影響を与えなかった(データ示さず)。嘔吐の増加は、硫酸鉄(II)において9/21の患者により、鉄(III)−ポリマルトース複合体において7/20の患者により報告された(p=0.75)。
Claims (9)
- 慢性炎症性腸疾患の患者における鉄欠乏状態の経口処置用薬剤を調製するための、炭水化物との鉄(III)複合化合物の使用。
- 前記炭水化物が、デキストランおよび水素化デキストラン、デキストリンおよび水素化デキストリンもしくは酸化デキストリン、ならびにプルラン、そのオリゴマーおよび水素化プルランからなる群から選択される、請求項1に記載の使用。
- 前記炭水化物が、酸化デキストリンまたは水素化デキストリンから選択される、請求項1または2に記載の使用。
- 前記鉄(III)複合化合物が、鉄(III)−ポリマルトース複合化合物である、請求項1または2に記載の使用。
- 前記鉄(III)−ポリマルトース複合化合物が、20000〜500000ダルトンの範囲の分子量を有する、請求項4に記載の使用。
- 前記鉄(III)複合化合物が、1つ以上のマルトデキストリンの酸化生成物との鉄(III)複合化合物である、請求項1から5の内の1つに記載の使用。
- 前記鉄(III)複合化合物が、鉄(III)塩水溶液と、アルカリ領域のpHにおいて次亜塩素塩水溶液での1つ以上のマルトデキストリンの酸化による生成物の水溶液とから得られ、そして、1つのマルトデキストリンが使われる場合、そのデキストロース当量は5〜37であり、いくつかのマルトデキストリンの混合物が使用される場合、その混合物のデキストロース当量は5〜37であり、そしてその混合物に含まれる個々のマルトデキストリンのデキストロース当量は2〜40である、請求項6に記載の使用。
- 前記薬剤が、顆粒、カプセル、ゲルまたはサシェ(sachet)のような錠剤、水溶液または乳液の剤形で存在する、請求項1〜7の内の1つに記載の使用。
- 前記慢性炎症性腸疾患が、クローン病および/または潰瘍性大腸炎である、請求項1〜8の内の1つに記載の使用。
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US7754702B2 (en) | 2006-01-06 | 2010-07-13 | Luitpold Pharmaceuticals, Inc. | Methods and compositions for administration of iron |
EP1997833A1 (de) | 2007-05-29 | 2008-12-03 | Vifor (International) Ag | Wasserlösliche Eisen-Kohlenhydratderivat-Komplexe, deren Herstellung und diese enthaltende Arzneimittel |
TWI468167B (zh) | 2007-11-16 | 2015-01-11 | 威佛(國際)股份有限公司 | 藥學組成物 |
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DE102010023850B4 (de) * | 2010-05-15 | 2013-12-19 | Johannes-Gutenberg-Universität Mainz | Funktionalisierte Nanopartikel mit verbesserter Bioverfügbarkeit |
WO2012104204A1 (en) | 2011-01-31 | 2012-08-09 | Vifor (International) Ag | Iron-carbohydrate complex compounds for the intravenous therapy of malaria |
CA2849926C (en) | 2011-10-13 | 2020-07-21 | Vidasym, Inc. | Iron-fiber composition, preparation and uses thereof |
US9796792B2 (en) | 2013-03-08 | 2017-10-24 | Vidasym, Inc. | Metal ion-functional fiber component complex compositions, preparation and uses thereof |
EP3091974B1 (en) | 2014-01-06 | 2020-04-01 | Shield TX (UK) Limited | Dosage regimen of ferric trimaltol |
GB201418710D0 (en) | 2014-10-21 | 2014-12-03 | Iron Therapeutics Holdings Ag | Dosage regimen |
CN114028423B (zh) * | 2021-12-13 | 2023-05-23 | 广东粤港澳大湾区国家纳米科技创新研究院 | 修饰的纳米氧化铁在制备预防和/或治疗炎性肠病的药物中的应用 |
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WO2003087164A1 (en) * | 2002-04-09 | 2003-10-23 | Pharmacosmos Holding A/S | Iron dextrin compounds for the treatment of iron deficiency anaemia |
WO2004037865A1 (de) * | 2002-10-23 | 2004-05-06 | Vifor (International) Ag | Wasserlösliche eisen-kohlenhydrat-komplexe, deren herstellung und diese enthaltende arzneimittel |
JP2004250383A (ja) * | 2003-02-20 | 2004-09-09 | Fujisawa Pharmaceut Co Ltd | 鉄分補給用組成物 |
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US5756715A (en) * | 1996-11-08 | 1998-05-26 | Abbott Laboratories | Process for making crystalline iron dextran |
DK172860B1 (da) | 1998-03-25 | 1999-08-16 | Pharmacosmos Holding As | Jerndextranforbindelse til anvendelse som komponent i et terapeutisk middel til forebyggelse af eller behandling af jernman |
IT1301728B1 (it) * | 1998-06-16 | 2000-07-07 | Therapicon Srl | Preparazione di un complesso antianemico. |
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WO2002083739A2 (en) | 2001-04-10 | 2002-10-24 | Danisco Usa, Inc. | Polymerization of mono and disaccharides with monocarboxylic acids and lactones |
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2005
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2006
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- 2006-08-22 AU AU2006283895A patent/AU2006283895B2/en not_active Ceased
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- 2006-08-22 WO PCT/EP2006/065532 patent/WO2007023154A2/de active Application Filing
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- 2006-08-22 CN CNA2006800305747A patent/CN101247813A/zh active Pending
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- 2006-08-22 US US12/064,053 patent/US20080234226A1/en not_active Abandoned
- 2006-08-22 EP EP06778319A patent/EP1924270B1/de not_active Not-in-force
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WO2003087164A1 (en) * | 2002-04-09 | 2003-10-23 | Pharmacosmos Holding A/S | Iron dextrin compounds for the treatment of iron deficiency anaemia |
WO2004037865A1 (de) * | 2002-10-23 | 2004-05-06 | Vifor (International) Ag | Wasserlösliche eisen-kohlenhydrat-komplexe, deren herstellung und diese enthaltende arzneimittel |
JP2004250383A (ja) * | 2003-02-20 | 2004-09-09 | Fujisawa Pharmaceut Co Ltd | 鉄分補給用組成物 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2022525824A (ja) * | 2020-02-24 | 2022-05-20 | 中国科学院昆明▲動▼物研究所 | トランスフェリンの発現量を検出するための試薬の、腸管免疫寛容不均衡疾患の診断試薬またはキットの調製における応用 |
JP7321252B2 (ja) | 2020-02-24 | 2023-08-04 | 中国科学院昆明▲動▼物研究所 | トランスフェリンの発現量を検出するための試薬の、腸管免疫寛容不均衡疾患の診断試薬またはキットの調製における応用 |
Also Published As
Publication number | Publication date |
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DE502006006466D1 (de) | 2010-04-29 |
CN101247813A (zh) | 2008-08-20 |
PT1924270E (pt) | 2010-05-17 |
RU2411037C2 (ru) | 2011-02-10 |
MX2008002558A (es) | 2008-03-14 |
ES2343585T3 (es) | 2010-08-04 |
EP1924270B1 (de) | 2010-03-17 |
US20080234226A1 (en) | 2008-09-25 |
KR101051171B1 (ko) | 2011-07-22 |
BRPI0614875A2 (pt) | 2011-04-19 |
WO2007023154A3 (de) | 2007-05-18 |
AU2006283895A1 (en) | 2007-03-01 |
PL1924270T3 (pl) | 2010-08-31 |
KR20080038432A (ko) | 2008-05-06 |
EP1924270A2 (de) | 2008-05-28 |
ATE460940T1 (de) | 2010-04-15 |
WO2007023154A2 (de) | 2007-03-01 |
CA2617510C (en) | 2013-01-08 |
DK1924270T3 (da) | 2010-07-19 |
AU2006283895B2 (en) | 2011-06-16 |
RU2008111148A (ru) | 2009-09-27 |
CA2617510A1 (en) | 2007-03-01 |
EP1757299A1 (de) | 2007-02-28 |
JP4997241B2 (ja) | 2012-08-08 |
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