Polymeric inhibitors of platelet aggregation. II. Copolymers of dipyridamole and related drugs with N-vinylpyrrolidone

Bamford, C. H.; Middleton, I. P.; Al-Lameé, Kadem

doi:10.1016/0304-4165(87)90068-7

Cited by 13 publications

(9 citation statements)

References 16 publications

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“…This behaviour is commonly ascribed to the inhibition by dipyridamole of intra-cellular phosphodiesterase, an enzyme which decomposes c-AMP. When dipyridamole is coupled to poly-NVP its potentiating ability is very greatly reduced, or eliminated (Bamford et aI 1987a). However, the adduct is just as potent as dipyridamole as a phosphodiesterase inhibitor when assessed in vitro, hence we have concluded that the polymer chains of the adduct prevent penetration of the platelet membrane and so preclude access to intracellular phosphodiesterase (Bamford et al 1987a).…”

Section: Adducts Of Bw 245c With Polymersmentioning

confidence: 81%

“…Very different results (Bamford et al 1987a) are obtained with the vasodilator dipyridamole (17), which is also an inhibitor of platelet ,aggregation. This drug is much less demanding in its steric requirements for interaction with its receptor, indeed one piperidine ring may be removed without major changes in activity.…”

Section: Adducts Of Bw 245c With Polymersmentioning

confidence: 95%

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Modification of polymers for cardiovascular applications—some routes to bioactive hydrophilic polymers

et al. 1989

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This paper is concerned with the activation of platelets by polymers, a keyprocess in the behaviour of prosthetic devices in contact with blood. Platelets are activated by contact with many different types of polymer surfaces, which must therefore be regarded as thrombogenic. Two procedures for reducing thrombogenicity are discussed: (i) the chemical attachment of inhibitors of platelet aggregation and (ii) gross modification of the nature of the surface, e.g. by making it more hydrophilic. For purposes of (i) the potent prostaglandin analogue BW 245C has been used, while for (ii) grafting of poly(ethylene glycol) (PEG) has been explored. Both methods give greatly reduced platelet adhesion in in vitro tests. The second part of the paper deals with the properties of adducts of inhibitors of platelet aggregation (BW 245C, dipyridamole) with water-soluble macromolecules [poly(N-vinyl pyrrolidone), PEG, dextran]. Adducts have been synthesized with terminal and side-chain coupling. On adduction the two inhibitors mentioned show opposite types of behaviour: the molar activity of BW 245C is dramatically reduced, but that of dipyridamole is significantly increased. Remarkable synergistic effects have been recorded for BW 245C adducts. These observations are .interpreted in terms of differences in stereochemistry in the drug-receptor interactions. Appropriate chemical techniques for coupling are outlined, attention being drawn to the special uses of haloalkyl-and haloacyloisocyanates and 2-isocyanatoethyl methacrylate as reagents.

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Section: Adducts Of Bw 245c With Polymersmentioning

confidence: 81%

Section: Adducts Of Bw 245c With Polymersmentioning

confidence: 95%

Modification of polymers for cardiovascular applications—some routes to bioactive hydrophilic polymers

et al. 1989

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“…The dipyridamole-theophyllin e ester was found to be twice as potent as theophyllin e and four times more powerful than dipyridamole in potentiating the inhibitory action of BW245c against ADP (10 ¹ M) induced platelet aggregation. This work also revealed that a monomethacrylate ester (DIMA), prepared by coupling dipyridamole with methacrylic acid using carbonyl di-imidazole as a coupling agent [25], also potentiated the inhibitory action of BW245c to a greater degree than dipyridamole itself. When platelet activating factor (PAF), rather than ADP, was used to induce platelet aggregation however, dipyridamole became far more active (» twenty times) in potentiating BW245c inhibitory activity.…”

Section: Dipyridamolementioning

confidence: 93%

Professor Bamford's research in the field of biomaterials

Middleton

Al-Lameé²,

Paprotny

2000

Journal of Biomaterials Science, Polymer Edition

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Professor Bamford was regarded by many as the greatest British polymer chemist of the twentieth century and when Bam passed away in November 1999 tribute was quite rightly made to his considerable achievements in the field of polymer science. The aim of this paper is to highlight Bam's contribution to biomaterials research that occupied his attention for over 15 years after his official retirement. In particular a review of the synthetic methods employed by Bam for the modification of polymers to improve haemocompatibility and to function as affinity separation membranes for protein purification is presented.

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“…A relevant example is the vasodilator dipyridamole (Persantin, Boehringer, Mannheim, Germany) [10) which may be esterified with methacrylic acid to yield the monomer [11) (DIMA). This ester provides a useful method for coupling dipyridamole to polymers.…”

Section: Antiplatelet Agentsmentioning

confidence: 99%

“…[11] Scheme 1 [10] Functionalization of polymers: passivation [17] [16] Many types of polymer require additional functionalization to allow drugs to be coupled to them. Two reagents which have proved very effective for such purposes are haloisocyanates (more properly called halo-alkyl isocyanates or halo acylisocyanates), two examples of which are shown in [12] and 2-isocyanatoethyl methacrylate [13].…”

Section: Antiplatelet Agentsmentioning

confidence: 99%

Modification of Biomaterials to Improve Blood Compatibility

et al. 1992

Int J Artif Organs

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Polymeric inhibitors of platelet aggregation. II. Copolymers of dipyridamole and related drugs with N-vinylpyrrolidone

Cited by 13 publications

References 16 publications

Modification of polymers for cardiovascular applications—some routes to bioactive hydrophilic polymers

Modification of polymers for cardiovascular applications—some routes to bioactive hydrophilic polymers

Professor Bamford's research in the field of biomaterials

Modification of Biomaterials to Improve Blood Compatibility

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