Manufacture of pharmaceutical dosage forms |
| OF THE INVENTION The present invention is directed to solid, unit dosage forms primarily for oral ... |
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Device comprising liner for protecting fluid sensitive medicament |
| OF THE DRAWING FIGURES Turning now to the drawings in detail, which are examples of various ... |
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In situ active compound assembly |
| I claim: 1. A method to modify a target condition contained within an environment with a conjugate ... |
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Inhibition of nitric oxide-mediated hypotension and septic shock with iron-containing hemoprotein |
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Anti-bronchoconstriction 2-(4'-pyridinyl)-thiazole derivatives, composition, and method of use therefor |
| We claim: 1. A compound having the structural formula I ##STR4## wherein R is cyano, ##STR5## --C(.... |
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Antioxidant-induced apoptosis in vascular smooth muscle cells |
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Treatment of climacteric disorders with nitric oxide synthase substrates and/or donors |
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Specifically .beta.-.beta. cross-linked hemoglobins and method of preparation
| Details |
Inventors: Kluger, Ronald; Wodzinska, Jolanta;
Assignee: The University of Toronto Innovations Foundation (Toronto, CA)
Primary Examiner: Wityshyn; Michael G.
Assistant Examiner: Touzeau; P. Lynn
Attorney, Agent or Firm: Bereskin & Parr
A modified hemoglobin comprising hemoglobin which is cross-linked with a cross-linking reagent. The cross-linking reagent is selected such that the .beta.-chains are cross-linked within the 2,3-diphosphoglycerate binding site and the linkage distance between the .beta.-chains is between about 5 to 9 angstroms. A method of preparing the modified hemoglobin and its use as a blood substitute or a plasma expander are also described. |
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DETAILED DESCRIPTION The present invention provides a modified hemoglobin comprising hemoglobin which is cross-linked with a cross-linking reagent, said cross-linking reagent being selected such that the . beta. -chains are cross-linked within the 2,3-diphosphoglycerate binding site and the distance between the . beta. -chains is between about 5 to 9 angstroms. Preferably, the cross-linking reagent is selected such that the . beta. -chains are cross-linked between the epsilon amino group of lysine-82 of one chain and the alpha amino group of valine-1 of the other chain and the distance between the . beta. -chains is about 7 angstroms. In accordance with one embodiment of the invention a modified hemoglobin is provided which is obtained by cross-linking hemoglobin with a cross-linking reagent comprising an aromatic- or aliphatic-derived acyl material having at least two anionic leaving groups each anionic leaving group being adjacent to an electrophile group, said cross-linking reagent being selected such that a first electrophile group reacts covalently with the epsilon group lysine 82 of a first . beta. chain of said hemoglobin and a second electrophile group reacts covalently with the alpha amino group valine-1 of a second . beta. chain of said modified hemoglobin whereby said hemoglobin is intramolecularly cross-linked between said beta chains such that the distance between the . beta. chains at said cross-link is between about 5 to 9 angstroms. Preferably, the cross-linking reagent comprises an aromatic- or aliphatic-derived acyl material having at least three anionic leaving groups and wherein a third electrophile group reacts covalently with the epsilon group lysine 82 of said second . beta. chain of said hemoglobin or the alpha amino group valine-1 of said first . beta. chain of said hemoglobin. The cross-linking reagent may comprise an aromatic- or aliphatic-derived acyl material having at least four anionic leaving groups and a fourth electrophile group may react covalently with the alpha amino group valine-1 of said first
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