EP0187547A2
Expired / Lapsed
EP
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Synthetic polymeric drugs
Assignee: Czech Academy of Sciences
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Filing: 1985-12-31
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Granted: —
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Expires: 2005-12-31
Abstract
Abstract A polymeric drug comprising an inert synthetic polymeric carrier combined through aminoacid or peptide spacers with a bioactive molecule, a targeting moiety, and an optional cross-linkage, comprises: (a) 5.0 to 99.7 mol % of units derived from N-(2-hydroxypropyl) methacrylamide, (b) 0.2 to 20.0 mol % of units derived from an N-methacryloylated peptide, the peptide groups being bound to a bioactive moiety, (c) 0.1 to 94.8 mol % of units derived from N-methacrylamide, N-methacrylic acid or an N-meth- ecryloylated aminoacid or peptide, to which are bound a determinant capable of interacting with specific receptors on cell surfaces, (d) optionally, 0 to 5 mol % of units derived from an N-methacryloylated peptide, the peptide groups being bound to a linking group which is similarly attached to a similar peptide group attached to another polymer chain, and (e) optionally, as a bioassay label, Q to 2 mol % of units derived from N-methacryloylated tyrosinamide.
Inventors
- 👤 Jindrich The Institute Of Kopecek
- 👤 Pavla The Institute Of Rejmanova
- 👤 Jiri The Institute Of Strohalm
- 👤 Karel The Institute Of Ulbrich
- 👤 Blanka The Institute Of Rihova
- 👤 Vladimir The Institute Of Chytry
- 👤 John B. Department Of Biological Sciences Lloyd
- 👤 Ruth Department Of Biological Sciences Duncan
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-27 17:24
CPC Classifications
A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6835; A61K47/6883; A61K47/56; A61K47/58; A61P; A61P35/00; Y; Y10; Y10S; Y10S530/00; Y10S530/81; Y10S530/811; Y10S530/812; Y10S530/815; Y10S530/816
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
218 words
A polymeric drug comprising an inert synthetic polymeric carrier combined through peptide spacers with a bioactive molecule, and with a targeting moiety, and an optional cross-linkage, which comprises (a) 5.0 to 99.7 mol of units derived from N-(2-hydr-oxypropyl)methacrylamide, (b) 0.2 to 20.0 mol % of units derived from an N-methacryloylated peptide, the peptide groups being bound to a bioactive molecule and being Gly-Gly, Gly-Phe-Gly, Gly-Phe-Phe, Gly-Leu-Gly, Gly-Val-Ala, Gly-Phe-Ala, Gly-Leu-Phe, Gly-Leu-Ala, Ala-Val-Ala, Gly-Phe-Leu-Gly, Gly-Phe-Phe-Leu, Gly-Leu-Leu-Gly, Gly-Phe-Tyr-Ala, Gly-Phe-Gly-Phe, Ala-Gly-Val-Phe, Gly-Phe-Phe-Gly, Gly-Phe-Leu-Gly-Phe, or Gly-Gly-Phe-Leu-Gly-Phe, and being subject to intracellular lysosomal hydrolysis, (c) 0.1 to 94.8 mol % of units derived from N-methacrylamide,N-methacrylic acid or an N-methacryloylated aminoacid or peptide, to which are bound a determinant capable of interacting with specific receptors on cell surfaces, the aminoacid or peptide being Leu, Phe, Gly-Gly, Gly-Leu-Gly, Gly-Val-Ala, Gly-Phe-Ala, Gly-Leu-Phe, Gly-Leu-Ala, Ala-Val-Ala, Gly-Phe-Leu-Gly, Gly-Phe-Phe-Leu, Gly-Leu-Leu-Gly, Gly-Phe-Tyr-Ala, Gly-Phe-Gly-Phe, Ala-Gly-Val-Phe, Gly-Phe-Phe-Gly, Gly-Phe-Leu-Gly-Phe, or Gly-Gly-Phe-Leu-Gly-Phe, (d) optionally, O to 5 mol % of units derived from an N-methacryloylated peptide, the peptide groups being bound to a linking group which is similarly attached to a similar peptide group attached to another polymer chain, the peptide being, Gly-Leu-Gly, Gly-Val-Ala, Gly-Phe-Ala, Gly-Leu-Phe, Gly-Leu-Ala, Ala-Val-Ala, Gly-Phe-Leu-Gly, Gly-Phe-Phe-Leu, Gly-Leu-Leu-Gly, Gly-Phe-Tyr-Ala, Gly-Phe-Gly-Phe, Ala-Gly-fal-Phe. Gly-Phe-Phe-Gly, Gly-Phe-Leu-Gly-Phe, or Gly-Gly-Phe-Leu-Gly-Phe. and (e) optionally, as a bioassay label, 0 to 2 mol of units derived from K-methacryloylated tyrosinamide.
Claim 2
Dependent Claim
218 words
A polymeric drug comprising an inert synthetic polymeric carrier combined through peptide spacers with a bioactive molecule, and with a targeting moiety, and an optional cross-linkage, which comprises (a) 5.0 to 99.7 mol of units derived from N-(2-hydr-oxypropyl)methacrylamide, (b) 0.2 to 20.0 mol % of units derived from an N-methacryloylated peptide, the peptide groups being bound to a bioactive molecule and being Gly-Gly, Gly-Phe-Gly, Gly-Phe-Phe, Gly-Leu-Gly, Gly-Val-Ala, Gly-Phe-Ala, Gly-Leu-Phe, Gly-Leu-Ala, Ala-Val-Ala, Gly-Phe-Leu-Gly, Gly-Phe-Phe-Leu, Gly-Leu-Leu-Gly, Gly-Phe-Tyr-Ala, Gly-Phe-Gly-Phe, Ala-Gly-Val-Phe, Gly-Phe-Phe-Gly, Gly-Phe-Leu-Gly-Phe, or Gly-Gly-Phe-Leu-Gly-Phe, and being subject to intracellular lysosomal hydrolysis, (c) 0.1 to 94.8 mol % of units derived from N-methacrylamide,N-methacrylic acid or an N-methacryloylated aminoacid or peptide, to which are bound a determinant capable of interacting with specific receptors on cell surfaces, the aminoacid or peptide being Leu, Phe, Gly-Gly, Gly-Leu-Gly, Gly-Val-Ala, Gly-Phe-Ala, Gly-Leu-Phe, Gly-Leu-Ala, Ala-Val-Ala, Gly-Phe-Leu-Gly, Gly-Phe-Phe-Leu, Gly-Leu-Leu-Gly, Gly-Phe-Tyr-Ala, Gly-Phe-Gly-Phe, Ala-Gly-Val-Phe, Gly-Phe-Phe-Gly, Gly-Phe-Leu-Gly-Phe, or Gly-Gly-Phe-Leu-Gly-Phe, (d) optionally, O to 5 mol % of units derived from an N-methacryloylated peptide, the peptide groups being bound to a linking group which is similarly attached to a similar peptide group attached to another polymer chain, the peptide being, Gly-Leu-Gly, Gly-Val-Ala, Gly-Phe-Ala, Gly-Leu-Phe, Gly-Leu-Ala, Ala-Val-Ala, Gly-Phe-Leu-Gly, Gly-Phe-Phe-Leu, Gly-Leu-Leu-Gly, Gly-Phe-Tyr-Ala, Gly-Phe-Gly-Phe, Ala-Gly-fal-Phe. Gly-Phe-Phe-Gly, Gly-Phe-Leu-Gly-Phe, or Gly-Gly-Phe-Leu-Gly-Phe. and (e) optionally, as a bioassay label, 0 to 2 mol of units derived from K-methacryloylated tyrosinamide.
Claim 3
Dependent Claim
27 words
A polymeric drug according to claim 1, in which the determinant is a monosaccharide, disaccharide or oligosaccharide bound by an amide linkage, an antibody or a protein.
Claim 4
Dependent Claim
19 words
A polymeric drug according to claim 2, in which the saccharide determinant is galactose, galactosamine, glucosamine, mannosamine or fucosylamine.
Claim 5
Dependent Claim
16 words
A polymeric drug according to claim 1, in which the determinant is IgG or anti-θ antibody.
Claim 6
Dependent Claim
40 words
A polymeric drug according to any of claims 1 to 4, in which the bioactive moiety is an anti-cancer agent, an antimicrobial agent, an antiparasitic agent, an anti-inflammatory agent, a cardio-vascular drug, or a drug acting on the nervous system.
Claim 7
Dependent Claim
28 words
A polymeric drug according to any of claims 1 to 5, in which the bioactive moiety is daunomycin,puromycin, adriamycin, melphalan isopropyl ester (sarcolysine), bleomycin, desferioxamine, bestatin or tritylcysteine.
Claim 8
Dependent Claim
48 words
A polymeric drug according to any of claims 1 to 6, in which the linking group of (d) is of the type -(aminoacid)-NH(CH 2 ) x NH-(aminoacid)-, where x is an integer of from 1 to 12, and which is attached to adjacent peptide groups by amide linkages.
Claim 9
Dependent Claim
31 words
A polymeric drug according to claim 7, in which x is 6 and the aminoacid is Phe, Tyr, Ala, Gly, or Leu, or x is 2 and the aminoacid is Ala.
Claim 10
Dependent Claim
46 words
A polymeric drug according to any of claims 1 to 8, in which the bioactive moiety is daunomycin, the determinant is galactose, galactosamine or fucosylamine, and, when the compound is cross-linked, the cross-linking spacer is Gly-Phe-Leu-Gly, and the linking group is -(Phe)NH(CH 2 ) 6 NH(Phe)-.
Claim 11
Dependent Claim
52 words
A process for the synthesis of a polymeric drug according to any of claims 1 to 9, which comprises copolymerising HPMA with either an N-methacryloylated aminoacid or peptide or the p-nitrophenyl ester thereof, and reacting the resultant copolymer with a reactive bioactive molecule, a reactive determinant, and, optionally, a diamino cross-linking agent.
Claim 12
Dependent Claim
56 words
A process for the synthesis of a polymeric drug according to any of claims 1 to 9, which comprises copolymerising HPMA, an N-methacryloylated determinant or N-methacryloylated aminoacid or peptidyl determinant, and either an N-methacryloylated peptide or the p-nitrophenyl ester thereof, and reacting the resultant copolymer with a reactive bioactive molecule and, optionally, a diamino cross-linking agent.
Claim 13
Dependent Claim
23 words
A process according to claim 10 or 11, in which N-methacryloylated tyrosinamide is also included in the copolymersiation step as a bioassay label.
Claim 14
Dependent Claim
24 words
A pharmaceutical composition, which comprises at least one polymeric drug according to any of claims 1 to 9 and an inert, physiologically acceptable carrier.
Claim 15
Dependent Claim
23 words
A pharmaceutical composition according to claim 13, in which the carrier is a sterile aqueous medium and the composition is formulated for injection.
References Cited (Backward Citations)
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