Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – From carboxylic acid or derivative thereof
Patent
1996-09-11
1998-10-06
Truong, Duc
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
From carboxylic acid or derivative thereof
5283291, 528330, 528331, 528332, 528335, 528363, C08G 6910
Patent
active
058177426
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to polyvalent polymer-based malonic acid derivatives having antiadhesive properties which cause intolerance reactions in vivo neither in their entirety nor in the form of degradation products, and to their preparation process and their use as medicaments and diagnostics.
The glycoconjugates present on the surface of eukaryotic cells represent specific bonding isotopes for transmembrane proteins which are called selectins. These selecting, which occur both in the endothelium and on the various circulating cells of the hematolymphatic system, undergo specific interactions with carbohydrate epitopes (ligands) of the other respective cell type (K. A. Karisson, TIPS 12, (1991), 265-272).
Synthetic analogs of selectin ligands are therefore promising candidates for anti-inflammatories and anticoagulants. Carbohydrate ligands also play a decisive role as recognition domains for viruses, bacteria and toxins, and therefore also in the initiation of the corresponding diseases (prophylaxis, diagnosis or treatment of bacterial and viral infections, inflammatory diseases, rheumatic arthritis, allergies, post-infarction syndrome, shock, apoplexy, acute and chronic organ rejection, vasculitis, sepsis, shock lung and the like).
Since cancer cells have a different pattern of these carbohydrate structures from healthy cells, this enables these mimetics to be used on the one hand as labels, and on the other hand for combating tumor cells, especially in metastasing tumors (S. I. Hakomori, Cancer Cells, December 1991, Volume 3, No. 12).
Sialylated and/or fucosylated carbohydrates, such as, for example, sialyl-Lewis X and sialyl-Lewis A, are of particular importance as mediators for cell adhesion (Lowe et al., Cell, 63, 475-85, 1990).
Simpler structures have already been proposed and in some cases synthesized with the aim of simplifying the very involved syntheses of these compounds while retaining or improving their bonding affinity to the corresponding selecting. Thus, for example, neuraminic acid has been replaced by lactic or glycolic acid and/or fucose has been replaced by glycerol or trifluoromethylfucose and/or N-acetylglucosamine has been replaced by glucosamine or glucose (PCT/US 92/09870). Substitution of neuraminic acid by sulfate or phosphate has also been described (PCT/CA 92/00245). Substitution of glucosamine by a chain of at least 2 carbon atoms is also described (WO 92/18610).
Treatment of inflammatory diseases with free oligosaccharides, which are said to bond to receptors instead of the naturally occurring ligands, is unsuccessful because of the very high amounts of oligosaccharide to be administered, since the affinity between the receptor and oligosaccharide is low (K.sub.D .about.10.sup.-4 M for the interaction between a monovalent galactoside and the corresponding lectin, D. T. Connolly et al. J. Biol. Chem. 257, 939, (1982)).
Divalent structures having a better bonding, in some cases, to the particular receptor are described by Wong et al. (J. Am. Chem. Soc. 115, 7549 (1993)) and in U.S. Pat. No. 5,254,676.
It is also known that an increased interaction between the receptor and ligand is achieved by coupling several ligands to a surface. Using the example of the virus protein hemagglutinin, which bonds to neuraminic acid on the cell surface, it has been possible to demonstrate how the use of a polymer having this polyvalent effect has a significant effect on the ligand-receptor interaction (monovalent K.sub.D =2.times.20.sup.-4 M, polyvalent K.sub.D= 3.times.10.sup.-7 M, A. Spaltenstein et al. J. Am. Chem. Soc. 113, 686 (1991)). Surfaces which have been used to date are liposomes (N. Yamazaki, Int. J. Biochem. 24, 99 (1991); WO 91/19501; WO 91/19502), polyacrylamides (R. C. Rathi et al. J. Polym. Sci.: Part A: Polym. Chem. 29, 1895 (1991), S. I. Nishimura et al. Macromolecules 24, 4236 (1991)), polylysine or sulfated polysaccharides. These polyvalent structures have the disadvantage of either having only a low stability in vivo or not being tolerated in vivo owing to their br
REFERENCES:
patent: 5254676 (1993-10-01), Sabesan
JP,A,01 127039 (Chuichi Hirayama).
Yamazaki et al., "Studies Carbohydrate-Bind. Prot. Use Liposome-Based Sys.-1. Prep. of Neoglycoprotein-Conjug. Liposomes & Feasibil. Use as Drug-Targeting Devices", J. Biochem. vol. 24 No. 1, (1992) pp. 99-104.
Nishimura et al., "Synthetic Glycoconjugates 2..sup.1 n-Pentenyl Glyocosides as Convenient Mediators Syntheses of New Types of Glycoprotein Models", Macromolecules, vol.24, (1991) pp. 4236-4241.
Spaltenstein et al., "Polyacrylamides Bearing Pendant a:Sialoside Groups Strongly Inhibit Agglutination of Erythrocytes by Influenza Virus", J. Am. Chem. Soc. vol. 113, (1991) pp. 686-687.
Connolly et al., "Binding and Endocytosis of Cluster Glycosides by Rabbit Hepatocytes", Journal of Biological Chemistry, vol. 25, No. 2, (1982) pp. 939-945.
Rathi et al., "N-(2-Hydroxypropyl)methacrylamide Copolymers Containing Pendant Saccharide Moieties . . . ", Journal of Polymer Science Part A: Polymer Chemistry, vol. 29, (1991), 1895-1902.
DeFrees et al., "Ligand Recognition by E-Selectin: Analysis of Conformation and Activity of Synthetic Monomeric and Bivalent Sialyl Lewis X Analogs", J. Am. Chem. Soc. vol. 115, (1993) p. 7549-7550.
Houghton et al., "Monoclonal Antibodies: Potential Applications to the Treatment of Cancer", Seminars in Oncology, vol. 13, No. 2, (1986) pp. 165-179.
Ravindranath et al., "An Epitope Common to Gangliosides O-Acetyl-G.sup.D3 and G.sup.D3 Recognized by Antibodies in Melanoma Patients After Active Specific Immunotherapy.sup.1 ", Cancer Res. vol. 49, (1989) pp. 3891-3897.
Eckelman et al., "In Vivo Diagnosis and Therapy of Human Tumors with Monoclonal Antibodies", Proceedings of a Symposium held in Naples, Italy, (1988) pp. 100-185.
Chem Abstract, vol. 1 ed: 56557, Sep. 4, 1997.
Bartnik Eckart
Horsch Brigitte
Kretzschmar Gerhard
Schmidt Wolfgang
Toepfer Alexander
Hoechst Aktiengesellschaft
Truong Duc
LandOfFree
Polymer-conjugated malonic acid derivatives and their use as med does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Polymer-conjugated malonic acid derivatives and their use as med, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polymer-conjugated malonic acid derivatives and their use as med will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-78130