Biologically active methylene blue derivatives
The present invention relates to a method of photodynamic therapy and to a method of inducing a photocytoxic effect which comprises applying to an area to be treated an effective amount of a compound of formula in which R 1 , R 2 , R 3 and R 4 each independently is an optionally -substituted linear, branched or cyclic hydrocarbon group, or R 1 and R 2 together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7- membered ring or R 3 and R 4 together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7- membered ring; and where X P− is a counteranion and P is 1, 2 or 3; except for the compounds in which —NR 1 R 2 and —NR 3 R 4 are the same and are selected from —N(CH 3 ) 2 or —N(CH 2 CH 3 ) 2 ; and exposing the area to light to activate the compound.
1. A method of antimicrobial photodynamic therapy in a patient in need of antimicrobial photodynamic therapy, which method comprises applying to ar area of a patient in need of antimicrobial photodynamic therapy to be treated an effective amount of a compound of formula
wherein
R 1 , R 2 , R 3 and R 4 each represent n-propyl;
R 1 , R 2 , R 3 and R 4 each represent n-butyl;
R 1 , R 2 , R 3 and R 4 each represent n-pentyl;
R 1 , R 2 , R 3 and R 4 each represent iso-pentyl;
R 1 represents n-butyl, R 2 represents n-butyl, R 3 represents n-propyl and R 4 represents n-propyl;
R 1 represents n-hexyl, R 2 represents n-hexyl, R 3 represents n-propyl and R 4 represents n-propyl;
R 1 , R 2 , R 3 and R 4 each represent iso-butyl;
R 1 represents n-butyl, R 2 represents n-butyl, R 3 represents iso-pentyl and R 4 represents iso-pentyl;
R 1 represents ethyl, R 2 represents ethyl, R 3 represents n-propyl and R 4 represents n-propyl;
R 1 represents n-pentyl, R 2 represents n-pentyl, R 3 n-propyl, R 4 represents n-propyl;
R 1 represents n-butyl, R 2 represents n-butyl, R 3 represents n-pentyl and R 4 represents n-pentyl;
R 1 represents ethyl, R 2 represents cyclohexyl, R 3 represents ethyl and R 4 represents cyclohexyl;
R 1 methyl, R 2 represents methyl, R 3 represents n-propyl, R 4 represents n-propyl; and
R 1 represents ethyl, R 2 represents ethyl, R 3 represents n-heptyl and R 4 represents n-heptyl;
and wherein X p− is a counteranion and P is 1, 2, or 3 ; and
exposing said area of said patient to light to activate the compound and to thereby effect said antimicrobial photodynamic therapy.
2. A method as claimed in claim 1 , wherein in said compound R 1 , R 2 , R 3 , and R 4 are the same and are selected from n-propyl, n-butyl, and n-pentyl.
3. A method as claimed in claim 1 , wherein R 1 , R 2 , R 3 and R 4 each represent n-pentyl.
4. A method as claimed in claim 1 , wherein R 1 , R 2 , R 3 and R 4 each represent n-pentyl and X P− represents Cl − , Br − , I − , F − , NO 3 − , HSO 4 − , CH 3 CO 2 − or a dianion namely SO 4 2− or H 2 PO 4 2− .
5. A method as claimed in claim 1 , wherein R 1 , R 2 , R 3 and R 4 each represent n-butyl.
6. A method according to claim 1 , wherein X P− is selected from F − , Br − , Cl − , I − , NO 3 − , SCN − , ClO 3 − , ClO 4 − , IO 3 − , BF 4 − , HSO 4 − , H 2 PO 4 − , CH 3 SO 4 − , N 3 − , SO 4 2− , HPO 4 2− , PO 4 3− , acetate, lactate, citrate, tartrate, glycolate, glycerate, glutamate, β-hydroxyglutamate, glucouronate, gluconate, malate and aspartate.
7. A method according to claim 1 , wherein the sum of the carbon atoms in alkyl side chains represented by R 1 , R 2 , R 3 and R 4 is from 14 to 40.
8. A method according to claim 1 , wherein said compound is provided in a composition which contains pharmaceutically acceptable carriers, excipients or adjuvants.
9. A method according to claim 1 , wherein said compound is provided in a composition which includes liposomes, nano-particles, colloidal suspensions, micelles, micro-emulsions, vesicles or nano-spheres.
10. A method according to claim 1 wherein said compound is provided in a composition, which includes a delivery vehicle or excipient selected from alcohols, dimethyl sulphoxide, water, saline, solubilisers, isotonising agents, pH regulators, dyes, gelling agents, thickeners, buffers and combinations thereof.
11. A method according to claim 1 , wherein said compound is part of a composite or conjugate.