Light stabilized in vivo stain composition and method of manufacture
View Patent ↗Photochemical demethylation reactions in solutions of thiazine dyes, in which the dye molecules act as both sensitizer and substrate, are reduced by quenching triple-state dye molecules, returning them to the unreactive ground state.
1. A method for reducing N-demethylation reactions in a thiazine dye solution, wherein the thiazine dye comprises:
(1) the compounds having the structures:
(2) the compounds having the structures:
the ratio of the combined areas of the 254 nm HPLC peaks representing the compounds in (1) to the combined areas of the peaks representing the N-demethylation derivatives in (2) being at least 6:1;
wherein molecules of the dye act as both the sensitizers and substrates in photochemical oxidative N-demethylation reactions in a thiazine dye solution, in which reactions at least a portion of the dye molecules absorb light and are converted to the singlet state,
at least a portion of the singlet-state dye molecules form triplet state molecules by intersystem crossing,
at least a portion of the triplet-state molecules react with ambient ground-state oxygen to produce singlet-state oxygen molecules, and
at least a portion of the singlet-state oxygen molecules N-methylate ground-state dye molecules,
the method comprising adding, after the thiazine dye solution is formed, a metal ion to the solution, wherein the metal ion quenches some of the triplet state dye molecules and returns them to the unreactive ground state.
2. The method of claim 1 wherein the metal ion is a heavy atom.
3. The method of claim 1 , wherein said metal ion is a zinc ion.
4. The method of claim 1 , wherein said metal ion is a sodium ion.
5. The method of claim 1 , wherein the metal ions are both zinc and sodium ions.
6. A method for at least partially reducing the oxidative demethylation of a thiazine dye, the method comprising the steps of:
providing a thiazine dye in solution; and
adding, after the thiazine dye solution is formed, a metal ion to the thiazine dye solution;
wherein the thiazine dye comprises:
(1) the compounds having the structures:
(2) the compounds having the structures:
the ratio of the combined areas of the 254 nm HPLC peaks representing the compounds in (1) to the combined areas of the peaks representing the compounds in (2) being at least 6:1;
and
wherein the metal ion quenches the thiazine dye to at least partially reduce the oxidative demethylation of the thiazine dye.
7. The method of claim 6 , wherein the metal ion is a heavy atom.
8. The method of claim 6 , wherein the total metal content of the thiazine dye solution is less than 0.2% by weight.
9. The method of claim 6 , wherein the step of adding the metal ion to the thiazine dye solution produces a thiazine dye solution comprising about 2% by weight or more of the metal ion.
10. The method of claim 6 , wherein the metal ion is any one or a combination of the compounds selected from the group consisting zinc, sodium, magnesium, chromium and silicon.
11. The method of claim 10 , wherein the metal ion is selected as a combination of zinc and sodium.
12. The method of claim 6 , wherein the metal ion is provided as a salt.
13. The method of claim 10 , wherein the thiazine dye solution comprises about 4% by weight zinc chloride and 9% by weight sodium chloride.
14. A method for reducing N-demethylation reactions in a thiazine dye solution, wherein the thiazine dye comprises:
the compounds having the structures
in which (a) comprises at least 58% of the total organic dye content of the composition;
wherein molecules of the dye act as both the sensitizers and substrates in photochemical oxidative N-demethylation reactions, in which reactions
at least a portion of the dye molecules absorb light and are converted to the singlet state,
at least a portion of the singlet-state dye molecules form triplet state molecules by intersystem crossing,
at least a portion of the triplet-state molecules react with ambient ground-state oxygen to produce singlet-state oxygen molecules, and
at least a portion of the singlet-state oxygen molecules N-methylate ground-state dye molecules,
the method comprising adding, after the thiazine dye solution is formed, a metal ion to the solution, wherein the metal ion quenches some of the triplet state dye molecules and returns them to the unreactive ground state.
15. The method of claim 14 wherein the metal ion is a heavy atom.
16. The method of claim 14 , wherein the metal ion is a zinc ion.
17. The method of claim 14 , wherein the metal ion is a sodium ion.
18. The method of claim 14 , wherein the metal ions are both zinc and sodium ions.
19. A method for at least partially reducing the oxidative demethylation of a thiazine dye, the method comprising the steps of:
providing a thiazine dye in solution; and
adding, after the thiazine dye solution is formed, a metal ion to the thiazine dye solution;
wherein the thiazine dye comprises:
the compounds having the structures
in which (a) comprises at least 58% of the total organic dye content of the composition;
wherein the metal ion quenches the thiazine dye to at least partially reduce the oxidative demethylation of the thiazine dye.