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US 6,083,485 AGranted
Near infrared radiation in-vivo diagnostic methods and dyes
AssigneesInstitut fur Diagnostikforschung GmbH, der Freien Universitat Berlin
InventorsKai Licha, Bjorn Riefke, Wolfhard Semmler, Ulrich Speck, Christoph-Stephan Hilger
Life of this patent
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Abstract
This invention relates to an in-vivo diagnostic method based on near infrared radiation (NIR radiation) that uses water-soluble dyes and their biomolecule adducts, each having specific photophysical and pharmaco-chemical properties, as a contrast medium for fluorescence and transillumination diagnostics in the NIR range, to new dyes and pharmaceuticals containing such dyes.
Claims7
An in-vivo diagnostic near infrared radiation method comprising:
- (a) administering a compound of the general formula I
- B.sub.1 --(F--W.sub.n).sub.m (I)
- wherein
- l represents a number from 0 to 6, n represents a number from 0 to 10 and m represents a number from 1 to 100;
- B is a biological detecting unit having a molecular weight of up to 30,000 that bonds to specific cell populations or selectively to receptors, or accumulates in tissues or tumours, or generally stays in the blood, or is a macromolecule that bonds non-selectively;
- F represents a dye showing maximum absorption in the range of 650 to 1200 nm having the general formula IIb ##STR10## wherein R.sup.3 to R.sup.12 are same or different, each independently representing a hydrogen atom, a residue B or W, or an alkyl or alkenyl residue containing up to 6 carbon atoms or an aryl or aralkyl residue containing up to 9 carbon atoms, said alkyl, alkenyl, aryl or aralkyl residue optionally carrying an additional residue W or W to each pair of adjacent residues R.sup.3 to R.sup.10 are annealed, with due regard for the interspersed atoms, 5- to 6-member rings that may be saturated, unsaturated or aromatic, and that may optionally carry residue R,
- R is a halogen atom, a hydroxy, carboxy, acetoxy, amino, nitro, cyano or sulfonic acid group or an alkyl, alkenyl, hydroxyalkyl, carboxyalkyl, alkoxy, alkoxycarbonyl, sulfoalkyl, alkylamino, dialkylamino or halogenalkyl residue containing up to 6 carbon atoms, an aryl, alkylaryl hydroxyaryl, carboxyaryl, sulfoaryl, arylamino, diarylamino, nitroaryl or halogenaryl residue containing up to 9 carbon atoms,
- s and t independently represent the numbers 0 to 1 on the condition that s and t do not represent the number 1 at the same time,
- X and Y are same or different, each independently representing an O, S, Se or Te or a --C(CH.sub.3).sub.2 --, --CH.dbd.CH-- or --CR.sup.13 R.sup.14 -- fragment,
- wherein R.sup.13 and R.sup.14 independently represent a hydrogen atom, a residue B or W, or an alkyl or alkenyl residue containing up to 6 carbon atoms or an aryl or aralkyl residue containing up to 9 carbon atoms, the alkyl, alkenyl, aryl or aralkyl residue optionally having an additional residue W;
- W represents a hydrophilic group that improves water-solubility, with the n-octanol-water distribution coefficient of the compound according to formula I being less than or equal to 2.0 for l=0;
- as well as their physiologically tolerable salts;
- (b) irradiating the compound with light in the near infrared range;
- and
- (c) recording the radiation produced by the compound.
12 more elements
A cyanine dye of the general formula V ##STR13## where Q is a fragment selected from the group consisting of ##STR14## and ##STR15## where R.sup.30 represents a hydrogen atom, a hydroxy group, a carboxy group, an alkoxy residue containing 1 to 4 carbon atoms or a chlorine atom, b is an integer 2 or 3, R.sup.31 represents a hydrogen atom or an alkyl residue containing 1 to 4 carbon atoms,
- X and Y independently represent an --O--, --S--, --CH.dbd.CH-- or --C(CH.sub.2 R.sup.32)(CH.sub.2 R.sup.33)-- fragment each,
- R.sup.20 to R.sup.29, R.sup.32 and R.sup.33 independently represent a hydrogen atom, a hydroxy group, a carboxy-, a sulfonic acid residue or a carboxyalkyl-, alkoxycarbonyl or alkoxyoxoalkyl residue containing up to 10 C atoms
- or a sulfoalkyl residue containing up to 4 C atoms, or a non-selectively bonding macromolecule or a residue of the general formula VI
- --(O).sub.v --(CH.sub.2).sub.o --CO--NR.sup.34 --(CH.sub.2).sub.s --(NH--CO).sub.q --R.sup.35 (VI)
- on the condition that, where X and Y are O, S, --CH.dbd.CH-- or --C(CH.sub.3).sub.2 -- at least one of the residues R.sup.20 to R.sup.29 corresponds to a non-selectively bonding macromolecule or a compound of the general formula VI, where
- o and s equal 0 or independently represent an integer between 1 and 6,
- q and v independently represent 0 or 1,
- R.sup.34 represents a hydrogen atom or a methyl residue,
- R.sup.35 represents an alkyl residue containing 3 to 6 C atoms and comprising 2 to n-1 hydroxy groups, with n being the number of C atoms, or an alkyl residue containing 1 to 6 C atoms that carries 1 to 3 additional carboxy groups, an aryl residue containing 6 to 9 C atoms or arylalkyl residue containing 7 to 15 C atoms, or a residue of the general formula IIId or IIIe ##STR16## on the condition that q is 1, or a non-selectively bonding macromolecule,
- R.sup.20 and R.sup.21, R.sup.21 and R.sup.22, R.sup.22 and R.sup.23, R.sup.24 and R.sup.25, R.sup.25 and R.sup.26, R.sup.26 and R.sup.27, together with the interspersed carbon atoms, form a 5- or 6-member aromatic or saturated annelled ring,
- and its physiologically tolerable salts.
8 more elements
Dependencies are inferred from the claim text.