JPS6156128A - ドキソルビシンおよびその類縁体と陰イオン性ポリマ−との新規配合体、その製造法、および該配合体を含有する制癌作用を有する医薬組成物 - Google Patents

ドキソルビシンおよびその類縁体と陰イオン性ポリマ−との新規配合体、その製造法、および該配合体を含有する制癌作用を有する医薬組成物

Info

Publication number: JPS6156128A
Authority: JP; Japan
Prior art keywords: doxorubicin; anionic polymer; polycarboxylate; analogs; drug
Prior art date: 1984-05-25
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.): Pending

Application number

JP60110620A

Other languages

English (en)

Japanese (ja)

Inventor

フランコ・ツミノ

ロモロ・アキレ・ガンベツタ

セルジオ・ペンコ

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Pfizer Italia SRL

Original Assignee

Farmitalia Carlo Erba SRL

Priority date (The priority date 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 date listed.)

1984-05-25

Filing date

1985-05-24

Publication date

1986-03-20

1985-05-24 Application filed by Farmitalia Carlo Erba SRL filed Critical Farmitalia Carlo Erba SRL

1986-03-20 Publication of JPS6156128A publication Critical patent/JPS6156128A/ja

Status Pending legal-status Critical Current

Links

AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 title claims description 33
239000000203 mixture Substances 0.000 title claims description 18
229960004679 doxorubicin Drugs 0.000 title claims description 16
229920006318 anionic polymer Polymers 0.000 title claims description 11
230000001093 anti-cancer Effects 0.000 title claims description 8
238000004519 manufacturing process Methods 0.000 title claims description 3
229920001577 copolymer Polymers 0.000 claims description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
238000009472 formulation Methods 0.000 claims description 8
229920005646 polycarboxylate Polymers 0.000 claims description 8
230000007062 hydrolysis Effects 0.000 claims description 7
238000006460 hydrolysis reaction Methods 0.000 claims description 7
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
150000001875 compounds Chemical class 0.000 claims description 6
KQRWYZDETCDVGB-TZSSRYMLSA-N (7s,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-9-(2-bromoacetyl)-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CBr)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 KQRWYZDETCDVGB-TZSSRYMLSA-N 0.000 claims description 2
239000003242 anti bacterial agent Substances 0.000 claims description 2
229940088710 antibiotic agent Drugs 0.000 claims description 2
238000004587 chromatography analysis Methods 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
239000003456 ion exchange resin Substances 0.000 claims 1
229920003303 ion-exchange polymer Polymers 0.000 claims 1
230000007935 neutral effect Effects 0.000 claims 1
239000011734 sodium Substances 0.000 claims 1
229940079593 drug Drugs 0.000 description 24
239000003814 drug Substances 0.000 description 24
229920000642 polymer Polymers 0.000 description 16
210000004027 cell Anatomy 0.000 description 13
229960000975 daunorubicin Drugs 0.000 description 13
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 12
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 12
206010028980 Neoplasm Diseases 0.000 description 11
241000699670 Mus sp. Species 0.000 description 10
208000032839 leukemia Diseases 0.000 description 10
230000000694 effects Effects 0.000 description 7
230000007774 longterm Effects 0.000 description 7
229940045799 anthracyclines and related substance Drugs 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
201000011510 cancer Diseases 0.000 description 5
230000004083 survival effect Effects 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 4
XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
239000002246 antineoplastic agent Substances 0.000 description 4
229940041181 antineoplastic drug Drugs 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
229960000908 idarubicin Drugs 0.000 description 4
238000000034 method Methods 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
206010025323 Lymphomas Diseases 0.000 description 3
241000699666 Mus <mouse, genus> Species 0.000 description 3
QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 3
230000001332 colony forming effect Effects 0.000 description 3
FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 3
230000009467 reduction Effects 0.000 description 3
238000002054 transplantation Methods 0.000 description 3
229960000834 vinyl ether Drugs 0.000 description 3
KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical group C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
206010070863 Toxicity to various agents Diseases 0.000 description 2
230000000052 comparative effect Effects 0.000 description 2
230000001472 cytotoxic effect Effects 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
238000011081 inoculation Methods 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
RONWGALEIBILOG-VMJVVOMYSA-N quinine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 RONWGALEIBILOG-VMJVVOMYSA-N 0.000 description 2
239000000243 solution Substances 0.000 description 2
238000000954 titration curve Methods 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
XVXGYZFARCOVHS-BINOZUKVSA-N (7s,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(=O)CO)C1 XVXGYZFARCOVHS-BINOZUKVSA-N 0.000 description 1
238000011725 BALB/c mouse Methods 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
239000006145 Eagle's minimal essential medium Substances 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
239000002253 acid Substances 0.000 description 1
229920005603 alternating copolymer Polymers 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229940126575 aminoglycoside Drugs 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
239000003817 anthracycline antibiotic agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
230000007890 cytotoxin activity Effects 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
230000005284 excitation Effects 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
239000003292 glue Substances 0.000 description 1
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
239000010931 gold Substances 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
230000035876 healing Effects 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
239000002609 medium Substances 0.000 description 1
239000002547 new drug Substances 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
229920000447 polyanionic polymer Polymers 0.000 description 1
229920002959 polymer blend Polymers 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000008569 process Effects 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
238000004448 titration Methods 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000035899 viability Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

JP60110620A 1984-05-25 1985-05-24 ドキソルビシンおよびその類縁体と陰イオン性ポリマ−との新規配合体、その製造法、および該配合体を含有する制癌作用を有する医薬組成物 Pending JPS6156128A (ja)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB848413464A GB8413464D0 (en)	1984-05-25	1984-05-25	Anthracycline-anionic polymer conjugates
GB8413464		1984-05-25

Publications (1)

Publication Number	Publication Date
JPS6156128A true JPS6156128A (ja)	1986-03-20

Family

ID=10561522

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP60110620A Pending JPS6156128A (ja)	1984-05-25	1985-05-24	ドキソルビシンおよびその類縁体と陰イオン性ポリマ−との新規配合体、その製造法、および該配合体を含有する制癌作用を有する医薬組成物

Country Status (4)

Country	Link
JP (1)	JPS6156128A (fr)
BE (1)	BE902344A (fr)
DE (1)	DE3515178A1 (fr)
GB (2)	GB8413464D0 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2736255B2 (ja) *	1987-03-11	1998-04-02	フアルマシア・エ・アツプジヨン・エツセ・ピー・アー	イムノグロブリン結合体
EP0292964B1 (fr) *	1987-05-28	1995-04-05	Hiroshi Maeda	Dérivés de superoxyde dismutase, leur préparation et leur utilisation comme médicaments
IT1230505B (it) *	1988-10-11	1991-10-25	Sicor Spa	Procedimento per la conversione della daunorubicina in doxorubicina.
JPH03101616A (ja) *	1989-07-12	1991-04-26	Union Carbide Chem & Plast Co Inc	製薬学的活性誘導体の放出系
US5378456A (en) *	1993-03-25	1995-01-03	American Cyanamid Company	Antitumor mitoxantrone polymeric compositions
US5609867A (en)	1994-11-01	1997-03-11	American Cyanamid Company	Polymeric antitumor agents

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1602967A (en) *	1977-07-16	1981-11-18	Hercules Inc	Reaction prodcut of methotrexate with divinyl ether and maleic anhydride copolymer

1984
- 1984-05-25 GB GB848413464A patent/GB8413464D0/en active Pending
1985
- 1985-04-22 GB GB08510222A patent/GB2158078B/en not_active Expired
- 1985-04-26 DE DE19853515178 patent/DE3515178A1/de not_active Withdrawn
- 1985-05-03 BE BE0/214956A patent/BE902344A/fr not_active IP Right Cessation
- 1985-05-24 JP JP60110620A patent/JPS6156128A/ja active Pending

Also Published As

Publication number	Publication date
DE3515178A1 (de)	1985-11-28
GB2158078B (en)	1987-09-16
GB2158078A (en)	1985-11-06
GB8510222D0 (en)	1985-05-30
GB8413464D0 (en)	1984-07-04
BE902344A (fr)	1985-09-02

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