JP5693970B2 - ベンゾフェナントリジン構造を有する抗腫瘍薬およびそれらを含有する製剤 - Google Patents
ベンゾフェナントリジン構造を有する抗腫瘍薬およびそれらを含有する製剤 Download PDFInfo
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- JP5693970B2 JP5693970B2 JP2010547092A JP2010547092A JP5693970B2 JP 5693970 B2 JP5693970 B2 JP 5693970B2 JP 2010547092 A JP2010547092 A JP 2010547092A JP 2010547092 A JP2010547092 A JP 2010547092A JP 5693970 B2 JP5693970 B2 JP 5693970B2
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- sanguinarine
- benzophenanthridine
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- 238000002360 preparation method Methods 0.000 title description 6
- 239000002246 antineoplastic agent Substances 0.000 title description 4
- 229940041181 antineoplastic drug Drugs 0.000 title description 2
- OWUNMSGLMUPGEZ-UHFFFAOYSA-N benzo[k]phenanthridine Chemical group C1=CC=CC2=C3C4=CC=CC=C4C=CC3=CN=C21 OWUNMSGLMUPGEZ-UHFFFAOYSA-N 0.000 title description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 38
- INVGWHRKADIJHF-UHFFFAOYSA-N Sanguinarin Chemical compound C1=C2OCOC2=CC2=C3[N+](C)=CC4=C(OCO5)C5=CC=C4C3=CC=C21 INVGWHRKADIJHF-UHFFFAOYSA-N 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 15
- FCEXWTOTHXCQCQ-UHFFFAOYSA-N Ethoxydihydrosanguinarine Natural products C12=CC=C3OCOC3=C2C(OCC)N(C)C(C2=C3)=C1C=CC2=CC1=C3OCO1 FCEXWTOTHXCQCQ-UHFFFAOYSA-N 0.000 claims description 14
- 229940084560 sanguinarine Drugs 0.000 claims description 14
- YZRQUTZNTDAYPJ-UHFFFAOYSA-N sanguinarine pseudobase Natural products C1=C2OCOC2=CC2=C3N(C)C(O)C4=C(OCO5)C5=CC=C4C3=CC=C21 YZRQUTZNTDAYPJ-UHFFFAOYSA-N 0.000 claims description 14
- 229930015421 benzophenanthridine alkaloid Natural products 0.000 claims description 11
- FLZGFQFYDGHWLR-UHFFFAOYSA-N luteic acid Chemical group O1C(=O)C2=CC(O)=C(O)C(O)=C2C2=C1C(O)=C(O)C=C2C(=O)O FLZGFQFYDGHWLR-UHFFFAOYSA-N 0.000 claims description 10
- 210000000130 stem cell Anatomy 0.000 claims description 10
- 201000001441 melanoma Diseases 0.000 claims description 6
- -1 sanguinarine luteic acid salt Chemical class 0.000 claims description 6
- 229930013930 alkaloid Natural products 0.000 claims description 5
- 208000024719 uterine cervix neoplasm Diseases 0.000 claims description 5
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical class CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 4
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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- 150000008622 benzophenanthridines Chemical class 0.000 description 2
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
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- GIZKAXHWLRYMLE-UHFFFAOYSA-M sanguinarium chloride Chemical compound [Cl-].C1=C2OCOC2=CC2=C3[N+](C)=CC4=C(OCO5)C5=CC=C4C3=CC=C21 GIZKAXHWLRYMLE-UHFFFAOYSA-M 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
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- 239000008158 vegetable oil Substances 0.000 description 2
- BIABMEZBCHDPBV-BEBVUIBBSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCC BIABMEZBCHDPBV-BEBVUIBBSA-N 0.000 description 1
- WEEFNMFMNMASJY-UHFFFAOYSA-M 1,2-dimethoxy-12-methyl-[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium;chloride Chemical compound [Cl-].C1=C2OCOC2=CC2=CC=C3C4=CC=C(OC)C(OC)=C4C=[N+](C)C3=C21 WEEFNMFMNMASJY-UHFFFAOYSA-M 0.000 description 1
- YFWHNAWEOZTIPI-DIPNUNPCSA-N 1,2-dioctadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCCCC YFWHNAWEOZTIPI-DIPNUNPCSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- LLEJIEBFSOEYIV-UHFFFAOYSA-N Chelerythrine Natural products C1=C2OCOC2=CC2=CC=C3C4=CC=C(OC)C(OC)=C4C=[N+](C)C3=C21 LLEJIEBFSOEYIV-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RATMHCJTVBHJSU-UHFFFAOYSA-N Dihydrochelerythrine Natural products C1=C2OCOC2=CC2=C(N(C)C(O)C=3C4=CC=C(C=3OC)OC)C4=CC=C21 RATMHCJTVBHJSU-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000078511 Microtome Species 0.000 description 1
- 206010029098 Neoplasm skin Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
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- 230000009422 growth inhibiting effect Effects 0.000 description 1
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- 229930013397 isoquinoline alkaloid Natural products 0.000 description 1
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- 210000004072 lung Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
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- 239000001923 methylcellulose Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
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- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
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- LDWIWSHBGAIIMV-ODZMYOIVSA-M sodium;[(2r)-2,3-di(hexadecanoyloxy)propyl] 2,3-dihydroxypropyl phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCC LDWIWSHBGAIIMV-ODZMYOIVSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
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- JFJZZMVDLULRGK-URLMMPGGSA-O tubocurarine Chemical compound C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CCN3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 JFJZZMVDLULRGK-URLMMPGGSA-O 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
腫瘍学の第1の目的は、それが重篤な副作用を伴う場合でも、なんとしても腫瘍を完全に根絶することである;腫瘍治療の指針として、「primum non nocere」(「何よりもまず害を成すなかれ」)というモットーは使用されず、「primum succerere」(「何よりもまず救済を急務とする」)に置き換えることが好ましい。
現在、ベンゾフェナントリジンアルカロイド、特にサンギナリン(sanguinarine)、チェレリスリン(chelerythrine)、ケリドニン(chelidonine)およびそれらのルテイック酸(luteic acid)、ホスファチジン酸またはヒアルロン酸との塩が、多剤耐性腫瘍幹細胞に対する増殖抑制効果を有することが見出されている。
3.68gの塩化サンギナリンを、100mlのエタノールに溶解し、撹拌しながら3.6gのカリウムルテアート(potassium luteate)を加え、混合物を3時間反応させる。形成された塩化カリウムをろ別し、溶液を少量に濃縮する。5.6gの塩を得る。
3.7gの塩化サンギナリンを50mlのメタノールに溶解する;この溶液を撹拌しながら7.5gの1,2−ジパルミトイル−sn−グリセロ−3−ホスホ−rac−(1−グリセロール)1,2−ジパルミトイル−sn−グリセロ−3−ホスホ−rac−(1−グリセロール)ナトリウム塩を加え、混合物を撹拌しながら2時間放置する。得られた溶液を等量の塩化メチレンで希釈し、混合物を撹拌しながら0.5時間放置する。沈殿した塩化ナトリウムをろ別し、ろ液を真空下、35℃以下の温度下で、乾燥するまで濃縮した。70℃の融点を有する10gの赤みがかった固体を得る。
1gのサンギナリンを、15mlのジオキサンに室温で溶解し、300mlの生理食塩水中の5gのヒトアルブミン溶液に加える。混合物を撹拌しながら、無菌環境において4時間放置する。得られた混濁溶液を、超音波に1分間供する。懸濁液の外観および色が変化する。溶液を賦形剤を加えずに凍結乾燥する。
例3の手順に従って、サンギナリン溶液を調製し、この過程の完了後、10mgのサンギナリンを含有するであろう容器において、溶質を無菌条件下で凍結乾燥する。
サンギナリンルテアート(Sanguinarine luteate) 10.00mg
大豆レシチン 30.00mg
無水クエン酸 10.00mg
ラクトース 240.00mg
マンニトール 550.00mg
メチルセルロース 40.00mg
ステアリン酸パルミトイル 50.00mg
ベリー香料 40.00mg
グリチルリチン酸アンモニウム 0.5mg
タルク 10.00mg。
サンギナリンルテアート 10.00mg
大豆レシチン 50.00mg
蜜蝋 50.00mg
グリチルリチン酸アンモニウム 10.00mg
植物油 800.00mgまで適量。
サンギナリンルテアート 10.00mg
大豆レシチン 50.00mg
蜜蝋 50.00mg
スクシニルグリチルリチシン酸ナトリウム(Sodium succinyl−glycyrrhetate) 10.00mg
植物油 800.00mgまで適量。
ジパルミトイルホスファチジン酸サンギナリン塩 0.40g
プロピレングリコール 10.00g
ミリスチン酸イソプロピル 5.00g
セチルアルコール 5.00g
ポリソルベート80 3.00g
カルボマー 0.40g
パラヒドロキシ安息香酸メチル 0.10g
パラヒドロキシ安息香酸プロピル 0.05g
精製水 100gまで適量。
Claims (8)
- ベンゾフェナントリジンアルカロイドの塩を含み、該ベンゾフェナントリジンアルカロイドが、サンギナリン、チェレリスリンおよびケリドニンから選択され、該塩が、ルテイック酸塩、ヒアルロン酸塩およびホスファチジン酸塩から選択される、腫瘍治療用組成物。
- 前記アルカロイドがサンギナリンである、請求項1に記載の腫瘍治療用組成物。
- 前記塩がルテイック酸塩またはホスファチジン酸塩である、請求項1に記載の腫瘍治療用組成物。
- 前記ベンゾフェナントリジンアルカロイドの塩がサンギナリンルテイック酸塩である、請求項3に記載の腫瘍治療用組成物。
- 前記ベンゾフェナントリジンアルカロイドの塩がサンギナリンホスファチジン酸塩である、請求項3に記載の腫瘍治療用組成物。
- 前記ベンゾフェナントリジンアルカロイドの塩が、前記ベンゾフェナントリジンアルカロイドとアルブミンとの複合体からなるナノ粒子の形態で存在する、請求項1に記載の腫瘍治療用組成物。
- 前記腫瘍が多剤耐性腫瘍幹細胞の過剰増殖に由来する腫瘍である、請求項1に記載の腫瘍治療用組成物。
- 前記腫瘍が、中咽頭、頭部および頸部または子宮頸部の腫瘍あるいは黒色腫である、請求項1に記載の腫瘍治療用組成物。
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ITMI2008A000284 | 2008-02-22 | ||
IT000284A ITMI20080284A1 (it) | 2008-02-22 | 2008-02-22 | Agenti antitumorali a struttura benzofenantridinica e formulazioni che li contengono |
PCT/EP2009/001079 WO2009103476A1 (en) | 2008-02-22 | 2009-02-16 | Antitumoral agents with a benzophenanthridine structure and formulations containing them |
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JP5693970B2 true JP5693970B2 (ja) | 2015-04-01 |
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US (1) | US8337903B2 (ja) |
EP (1) | EP2242492B1 (ja) |
JP (1) | JP5693970B2 (ja) |
KR (1) | KR101633717B1 (ja) |
CN (1) | CN101951907A (ja) |
AU (1) | AU2009217020B2 (ja) |
CA (1) | CA2716019C (ja) |
DK (1) | DK2242492T3 (ja) |
ES (1) | ES2496669T3 (ja) |
IL (1) | IL207683A (ja) |
IT (1) | ITMI20080284A1 (ja) |
PL (1) | PL2242492T3 (ja) |
PT (1) | PT2242492E (ja) |
RU (1) | RU2492862C2 (ja) |
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Cited By (1)
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KR20100119551A (ko) * | 2008-02-22 | 2010-11-09 | 인데나 에스.피.에이 | 벤조페난트리딘 구조를 갖는 항종양제 및 그를 함유하는 제제 |
Families Citing this family (7)
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ITMI20080038A1 (it) * | 2008-01-11 | 2009-07-12 | Indena Spa | Formulazioni per il trattamento di mucositi indotte da terapia antitumorale o immunosoppressiva |
CN102764259A (zh) * | 2011-05-03 | 2012-11-07 | 中国科学院动物研究所 | 血根碱类化合物在制备防治癌症的药物中的用途和药物组合物 |
AU2013244472B9 (en) | 2012-04-03 | 2015-02-19 | The Shizuoka Chamber Of Commerce And Industry | Composition for improving resistance to environmental stress of plant and method for improving resistance to environmental stress of plant |
CN102887904B (zh) * | 2012-10-10 | 2015-01-14 | 广西师范大学 | 2,3-二氧乙基-5-甲基-8,9-二甲氧基苯并菲啶衍生物及其制备方法和应用 |
KR102456075B1 (ko) | 2015-10-15 | 2022-10-19 | 삼성디스플레이 주식회사 | 화합물 및 이를 포함하는 유기 발광 소자 |
CN110339171A (zh) * | 2018-04-03 | 2019-10-18 | 临沂大学 | 一种白屈菜红碱固体分散体 |
CN111467347A (zh) * | 2020-04-30 | 2020-07-31 | 河北医科大学第二医院 | 苯并菲啶生物碱类化合物用于制备ano1 编码的钙激活氯离子通道阻断剂的用途 |
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US4970212A (en) * | 1982-05-18 | 1990-11-13 | Nowicky Wassili | Method of treating human illnesses which compromise the ability to mount an effective immunological response |
US4769452A (en) * | 1986-02-07 | 1988-09-06 | Vipont Laboratories, Inc. | Production of purity benzo-c-phenanthridine alkaloid salts |
CA1340994C (en) * | 1989-09-21 | 2000-05-16 | Rudolf Edgar Dr. Falk | Treatment of conditions and disease |
GB9211659D0 (en) * | 1992-06-02 | 1992-07-15 | Indena Spa | New alkaloid derivatives,their use and pharmaceutical formulations containing them |
US6025365A (en) * | 1997-03-25 | 2000-02-15 | Arch Development Corp. | Chelerythrine and radiation combined tumor therapy |
JP2000109428A (ja) * | 1998-10-05 | 2000-04-18 | Taisho Pharmaceut Co Ltd | 咽頭粘膜用組成物 |
CH695417A5 (de) * | 2001-11-15 | 2006-05-15 | Ddr Wassyl Nowicky Dipl Ing | Verfahren zur Umsetzung von Alkaloiden. |
EP1459753A1 (en) * | 2003-03-18 | 2004-09-22 | Nowicky, Wassyl, Dipl.-Ing. DDr. | Quaternary chelidonine and alkaloid derivatives, process for their preparation and their use in the manufacture of medicaments |
ES2226567B1 (es) * | 2003-06-20 | 2006-07-01 | Universidad De Santiago De Compostela | Nanoparticulas de acido hialuronico. |
US20070166388A1 (en) * | 2005-02-18 | 2007-07-19 | Desai Neil P | Combinations and modes of administration of therapeutic agents and combination therapy |
ITMI20080284A1 (it) * | 2008-02-22 | 2009-08-23 | Indena Spa | Agenti antitumorali a struttura benzofenantridinica e formulazioni che li contengono |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20100119551A (ko) * | 2008-02-22 | 2010-11-09 | 인데나 에스.피.에이 | 벤조페난트리딘 구조를 갖는 항종양제 및 그를 함유하는 제제 |
KR101633717B1 (ko) | 2008-02-22 | 2016-06-27 | 인데나 에스.피.에이 | 벤조페난트리딘 구조를 갖는 항종양제 및 그를 함유하는 제제 |
Also Published As
Publication number | Publication date |
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ITMI20080284A1 (it) | 2009-08-23 |
WO2009103476A8 (en) | 2009-12-03 |
CA2716019C (en) | 2016-07-05 |
EP2242492B1 (en) | 2014-07-23 |
EP2242492A1 (en) | 2010-10-27 |
KR101633717B1 (ko) | 2016-06-27 |
PT2242492E (pt) | 2014-09-04 |
SI2242492T1 (sl) | 2014-10-30 |
US8337903B2 (en) | 2012-12-25 |
ES2496669T3 (es) | 2014-09-19 |
WO2009103476A1 (en) | 2009-08-27 |
CA2716019A1 (en) | 2009-08-27 |
US20100331525A1 (en) | 2010-12-30 |
RU2492862C2 (ru) | 2013-09-20 |
AU2009217020B2 (en) | 2013-11-28 |
IL207683A0 (en) | 2010-12-30 |
CN101951907A (zh) | 2011-01-19 |
PL2242492T3 (pl) | 2015-02-27 |
DK2242492T3 (da) | 2014-09-15 |
RU2010134570A (ru) | 2012-02-27 |
JP2011512370A (ja) | 2011-04-21 |
AU2009217020A1 (en) | 2009-08-27 |
IL207683A (en) | 2014-04-30 |
KR20100119551A (ko) | 2010-11-09 |
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