JP5469706B2 - 新規な葉酸代謝拮抗薬の組み合わせ療法 - Google Patents
新規な葉酸代謝拮抗薬の組み合わせ療法 Download PDFInfo
- Publication number
- JP5469706B2 JP5469706B2 JP2012144570A JP2012144570A JP5469706B2 JP 5469706 B2 JP5469706 B2 JP 5469706B2 JP 2012144570 A JP2012144570 A JP 2012144570A JP 2012144570 A JP2012144570 A JP 2012144570A JP 5469706 B2 JP5469706 B2 JP 5469706B2
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- Prior art keywords
- medicament
- vitamin
- administered
- administration
- folic acid
- 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
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Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
-
- 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
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
Description
(方法)
メチルマロン酸低下薬の単独、または葉酸との組み合わせがヒト腫瘍異種移植片モデルに及ぼす効果を評価するために、ヒトMX−1乳癌腫を有する雌性ヌードマウスを、ALIMTAを単独でまたは生理学的を越えた用量の葉酸またはビタミンB12(コバラミン)と一緒に用いて処置した。
1.葉酸
葉酸は、以下の選択肢の1つとして与える。選択肢1〜選択肢3の順序で好ましい。
1.葉酸の350〜600μg。
2.選択肢1を使用できない場合には、350μg〜600μgの範囲の葉酸を含有するマルチビタミンが許容され得る。
3.選択肢1または選択肢2のいずれも使用できない場合には、350μg〜1000μg用量の葉酸が許容され得る。
ビタミンB12を得て、1000μgを筋肉内注射として投与する。ビタミンB12の注射は、ALIMTAを用いた処置の約1〜3週間前に投与しなければならず、そのことは患者が研究療法を中断するまで約9週間毎に繰り返すべきである。
比較するデータは以下の通りである:
1)患者数と、ベースラインから補充された患者のベースライン個体群の統計学的データ;
2)第1の服用前、第2の服用前および研究している癌の種類に応じた各治療サイクル前のホモシステインレベルおよびメチルマロン酸レベルと、ベースラインレベル;
3)これらの十分に補充された患者におけるグレード3と4の血液学的な毒性;
4)これらの十分に補充された患者におけるグレード3と4の非血液学的な毒性。
疲労のグレード
神経運動
0) なしまたは変化なし
1) 主観的な脱力感;客観的な知見なし
2) 機能の有意な障害がない、中位の客観的な脱力感
3) 機能の障害を有する、客観的な脱力感
4) 運動麻痺
皮膚
0) なしまたは変化なし
1) 無症候性である散らばった黄斑、丘疹の皮疹または紅斑
2) かゆみ症を伴う無症候性の散らばった黄斑、丘疹の皮疹もしくは紅斑、または他の関連する皮疹の症状
3) 全身症候性の黄斑、丘疹または小胞の皮疹
4) 剥脱性の皮膚炎または潰瘍性の皮膚炎
表1
Claims (17)
- 葉酸及びビタミンB12と用いられる、ペメトレキセート二ナトリウム塩を含有するヒトにおける腫瘍増殖を抑制するための医薬であって、下記レジメで投与される医薬:
a.有効量の該医薬を投与し;
b.葉酸の0.3mg〜5mgを、該医薬の投与前に投与し;そして、
c.ビタミンB12の500μg〜1500μgを、該医薬の第1の投与の1〜3週間前に投与し、
該レジメは、該医薬の毒性の低下および抗腫瘍活性の維持を特徴とする、
上記医薬。 - 1000μgのビタミンB12が投与される、請求項1記載の医薬。
- ビタミンB12が筋肉内注射によって投与される、請求項1又は2記載の医薬。
- 350μg〜1000μgの葉酸が投与される、請求項1〜3のいずれかに記載の医薬。
- 葉酸及びビタミンB12と用いられる、ペメトレキセート二ナトリウム塩を含有するヒトにおける腫瘍増殖を抑制するための医薬であって、下記レジメで投与される医薬:
a.有効量の該医薬を投与し;
b.葉酸の0.3mg〜5mgを、該医薬の投与前に投与し;そして、
c.ビタミンB12の500μg〜1500μgを、該医薬の第1の投与の1〜3週間前に筋肉内注射によって投与し、
該レジメは、該医薬の毒性の低下および抗腫瘍活性の維持を特徴とする、
上記医薬。 - 1000μgのビタミンB12が投与される、請求項5記載の医薬。
- 350μg〜1000μgの葉酸が投与される、請求項5又は6記載の医薬。
- 葉酸及びビタミンB12と用いられる、ペメトレキセート二ナトリウム塩を含有するヒトにおける腫瘍増殖を抑制するための医薬であって、下記レジメで投与される医薬:
a.有効量の該医薬を投与し;
b.葉酸の0.3mg〜5mgを、該医薬の投与前に投与し;そして、
c.ビタミンB12の500μg〜1500μgを、該医薬の第1の投与の1〜3週間前に筋肉内注射によって投与し、そして該医薬の投与の間に24時間毎〜1680時間毎に繰り返し、
該レジメは、該医薬の毒性の低下および抗腫瘍活性の維持を特徴とする、
上記医薬。 - 1000μgのビタミンB12が投与される、請求項8記載の医薬。
- 350μg〜1000μgの葉酸が投与される、請求項8又は9記載の医薬。
- ヒトにおける腫瘍増殖を抑制するための、葉酸とビタミンB12と用いられる医薬の製造における、ペメトレキセート二ナトリウム塩の使用であって、ここで、
a.有効量の医薬を投与し;
b.葉酸の0.3mg〜5mgを、該医薬の投与前に投与し;そして、
c.ビタミンB12の500μg〜1500μgを、該医薬の第1の投与の1〜3週間前に投与し、
該レジメは、該医薬の毒性の低下および抗腫瘍活性の維持を特徴とする、
上記使用。 - 1000μgのビタミンB12が投与される、請求項11記載の使用。
- ビタミンB12が筋肉内注射によって投与される、請求項11または12記載の使用。
- 350μg〜1000μgの葉酸が投与される、請求項11〜13のいずれかに記載の使用。
- ビタミンB 12 の投与が、該医薬の投与の間に6週間毎〜12週間毎に繰り返される、請求項1〜4のいずれかに記載の医薬。
- ビタミンB 12 の投与が、該医薬の投与の間に6週間毎〜12週間毎に繰り返される、請求項5〜7のいずれかに記載の医薬。
- ビタミンB 12 の投与が、該医薬の投与の間に6週間毎〜12週間毎に繰り返される、請求項11〜14のいずれかに記載の使用。
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US21531000P | 2000-06-30 | 2000-06-30 | |
US60/215,310 | 2000-06-30 | ||
US23585900P | 2000-09-27 | 2000-09-27 | |
US60/235,859 | 2000-09-27 | ||
US28444801P | 2001-04-18 | 2001-04-18 | |
US60/284,448 | 2001-04-18 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002506715A Division JP5102928B2 (ja) | 2000-06-30 | 2001-06-15 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013213276A Division JP2014005304A (ja) | 2000-06-30 | 2013-10-11 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2012180381A JP2012180381A (ja) | 2012-09-20 |
JP2012180381A5 JP2012180381A5 (ja) | 2013-11-14 |
JP5469706B2 true JP5469706B2 (ja) | 2014-04-16 |
Family
ID=27396105
Family Applications (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002506715A Expired - Lifetime JP5102928B2 (ja) | 2000-06-30 | 2001-06-15 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2012144570A Expired - Lifetime JP5469706B2 (ja) | 2000-06-30 | 2012-06-27 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2013213276A Withdrawn JP2014005304A (ja) | 2000-06-30 | 2013-10-11 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2015087012A Withdrawn JP2015178501A (ja) | 2000-06-30 | 2015-04-21 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2016192173A Withdrawn JP2017019852A (ja) | 2000-06-30 | 2016-09-29 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2018156677A Withdrawn JP2018197265A (ja) | 2000-06-30 | 2018-08-23 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2020072098A Pending JP2020117536A (ja) | 2000-06-30 | 2020-04-14 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
Family Applications Before (1)
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---|---|---|---|
JP2002506715A Expired - Lifetime JP5102928B2 (ja) | 2000-06-30 | 2001-06-15 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
Family Applications After (5)
Application Number | Title | Priority Date | Filing Date |
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JP2013213276A Withdrawn JP2014005304A (ja) | 2000-06-30 | 2013-10-11 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2015087012A Withdrawn JP2015178501A (ja) | 2000-06-30 | 2015-04-21 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2016192173A Withdrawn JP2017019852A (ja) | 2000-06-30 | 2016-09-29 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2018156677A Withdrawn JP2018197265A (ja) | 2000-06-30 | 2018-08-23 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
JP2020072098A Pending JP2020117536A (ja) | 2000-06-30 | 2020-04-14 | 新規な葉酸代謝拮抗薬の組み合わせ療法 |
Country Status (11)
Country | Link |
---|---|
US (4) | US7053065B2 (ja) |
EP (1) | EP1313508B1 (ja) |
JP (7) | JP5102928B2 (ja) |
AT (1) | ATE359823T1 (ja) |
AU (1) | AU2001269688A1 (ja) |
CY (1) | CY1107649T1 (ja) |
DE (1) | DE60127970T2 (ja) |
DK (1) | DK1313508T5 (ja) |
ES (1) | ES2284660T3 (ja) |
PT (1) | PT1313508E (ja) |
WO (1) | WO2002002093A2 (ja) |
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WO2002002093A2 (en) * | 2000-06-30 | 2002-01-10 | Eli Lilly And Company | Combination containing an antifolate and methylmalonic acid lowering agent |
ES2417065T3 (es) | 2005-04-26 | 2013-08-05 | Trion Pharma Gmbh | Combinación de anticuerpos con glucocorticoides para el tratamiento del cáncer |
AU2007204410A1 (en) * | 2006-01-12 | 2007-07-19 | Novartis Ag | Combination of mTOR inhibitor and antipolate compound |
WO2010021843A1 (en) * | 2008-08-20 | 2010-02-25 | Eli Lilly And Company | Use of antifolates in patients with detectable levels of tff-1 for the cancer treatment |
US8501242B2 (en) | 2009-05-29 | 2013-08-06 | University Of Florida Research Foundation | Methods and compositions for treating neoplasia |
US10736969B2 (en) | 2010-12-21 | 2020-08-11 | Nektar Therapeutics | Multi-arm polymeric prodrug conjugates of pemetrexed-based compounds |
SI2854768T1 (sl) | 2012-05-30 | 2017-08-31 | Fresenius Kabi Oncology Limited | Farmacevtski sestavki pemetrekseda |
SG11201609981RA (en) | 2014-06-04 | 2016-12-29 | Thomas Helledays Stiftelse För Medicinsk Forskning | Mth1 inhibitors for treatment of inflammatory and autoimmune conditions |
WO2016187413A1 (en) | 2015-05-21 | 2016-11-24 | Musculoskeletal Transplant Foundation | Modified demineralized cortical bone fibers |
KR20180059430A (ko) * | 2015-07-30 | 2018-06-04 | 익스프레션 패톨로지, 인크. | 최적의 암 치료를 위한 FR-α 및 GART 단백질의 정량화 |
IL259512B2 (en) * | 2015-12-07 | 2024-03-01 | General Oncology Inc | Combination for effective treatment of metastatic cancer in patients |
CA3033083A1 (en) | 2016-08-12 | 2018-02-15 | L.E.A.F. Holdings Group Llc | Polyglutamated antifolates and uses thereof |
ES2914123T3 (es) | 2017-01-09 | 2022-06-07 | Shuttle Pharmaceuticals Inc | Inhibidores selectivos de la histona desacetilasa para el tratamiento de una enfermedad humana |
US11584733B2 (en) | 2017-01-09 | 2023-02-21 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
WO2019139921A1 (en) | 2018-01-09 | 2019-07-18 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
CA3090387A1 (en) | 2018-02-07 | 2019-08-15 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated pralatrexate and uses thereof |
EP3749317A4 (en) | 2018-02-07 | 2022-06-22 | L.E.A.F Holdings Group LLC | PEMETREXED ALPHA-POLYGLUTAMATE AND ASSOCIATED USES |
EP3755335A4 (en) * | 2018-02-14 | 2022-06-22 | L.E.A.F Holdings Group LLC | GAMMA POLYGLUTAMIC TETRAHYDROFOLATES AND THEIR USES |
US11771700B2 (en) | 2018-02-14 | 2023-10-03 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated lometrexol and uses thereof |
WO2023177894A1 (en) | 2022-03-18 | 2023-09-21 | Ideaya Biosciences, Inc. | Combination therapy comprising a mat2a inhibitor and an antimetabolite agent |
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2001
- 2001-06-15 WO PCT/US2001/014860 patent/WO2002002093A2/en active IP Right Grant
- 2001-06-15 DK DK01948214.0T patent/DK1313508T5/da active
- 2001-06-15 EP EP01948214A patent/EP1313508B1/en not_active Expired - Lifetime
- 2001-06-15 PT PT01948214T patent/PT1313508E/pt unknown
- 2001-06-15 AT AT01948214T patent/ATE359823T1/de active
- 2001-06-15 DE DE60127970T patent/DE60127970T2/de not_active Expired - Lifetime
- 2001-06-15 US US10/297,821 patent/US7053065B2/en not_active Expired - Lifetime
- 2001-06-15 ES ES01948214T patent/ES2284660T3/es not_active Expired - Lifetime
- 2001-06-15 JP JP2002506715A patent/JP5102928B2/ja not_active Expired - Lifetime
- 2001-06-15 AU AU2001269688A patent/AU2001269688A1/en not_active Abandoned
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2005
- 2005-11-29 US US11/288,807 patent/US20060079480A1/en not_active Abandoned
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2007
- 2007-06-07 CY CY20071100756T patent/CY1107649T1/el unknown
- 2007-07-11 US US11/776,329 patent/US7772209B2/en not_active Expired - Fee Related
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2010
- 2010-04-28 US US12/768,920 patent/US20100210583A1/en not_active Abandoned
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2012
- 2012-06-27 JP JP2012144570A patent/JP5469706B2/ja not_active Expired - Lifetime
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2013
- 2013-10-11 JP JP2013213276A patent/JP2014005304A/ja not_active Withdrawn
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2015
- 2015-04-21 JP JP2015087012A patent/JP2015178501A/ja not_active Withdrawn
-
2016
- 2016-09-29 JP JP2016192173A patent/JP2017019852A/ja not_active Withdrawn
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2018
- 2018-08-23 JP JP2018156677A patent/JP2018197265A/ja not_active Withdrawn
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2020
- 2020-04-14 JP JP2020072098A patent/JP2020117536A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
WO2002002093A3 (en) | 2003-02-06 |
DE60127970T2 (de) | 2007-12-20 |
US20060079480A1 (en) | 2006-04-13 |
JP2020117536A (ja) | 2020-08-06 |
ES2284660T3 (es) | 2007-11-16 |
PT1313508E (pt) | 2007-06-21 |
US7053065B2 (en) | 2006-05-30 |
JP2017019852A (ja) | 2017-01-26 |
DE60127970D1 (de) | 2007-05-31 |
DK1313508T5 (da) | 2017-03-20 |
US20030212038A1 (en) | 2003-11-13 |
ATE359823T1 (de) | 2007-05-15 |
US7772209B2 (en) | 2010-08-10 |
WO2002002093A2 (en) | 2002-01-10 |
JP2014005304A (ja) | 2014-01-16 |
US20080032948A1 (en) | 2008-02-07 |
JP2004501964A (ja) | 2004-01-22 |
JP5102928B2 (ja) | 2012-12-19 |
DK1313508T3 (da) | 2007-08-06 |
EP1313508B1 (en) | 2007-04-18 |
US20100210583A1 (en) | 2010-08-19 |
EP1313508A2 (en) | 2003-05-28 |
JP2018197265A (ja) | 2018-12-13 |
JP2015178501A (ja) | 2015-10-08 |
CY1107649T1 (el) | 2013-04-18 |
JP2012180381A (ja) | 2012-09-20 |
AU2001269688A1 (en) | 2002-01-14 |
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