Biologically active methylene blue derivatives

• US 7,915,254 B2
• Filed: 04/04/2008
• Issued: 03/29/2011
• Est. Priority Date: 05/30/2001
• Status: Expired due to Fees

• Current Assignee: Stanley Beames Brown, Stephen John Lyon
• Original Assignee: Photopharmica Limited
• Inventors: Vernon, David Ian, Brown, Stanley Beames, Mellish, Kirste Joanne, O'Grady, Cassandra Claire, Griffiths, John
• Primary Examiner(s): DRAPER, LESLIE A ROYDS
• Application Number:
  US12/078,805
• Publication Number:
  US 20080261960A1
• Time in Patent Office: 1,089 Days
• Field of Search: None
• US Class Current: 514/224.8
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 49/003 Thiazine dyes
• CPC Class Codes: A61K 8/4986 with sulfur as the only hetero atom
• CPC Class Codes: A61L 2/0029 Radiation
• CPC Class Codes: A61L 2/0082 using chemical substances
• CPC Class Codes: A61L 2/08 Radiation
• CPC Class Codes: A61L 2/232 layered or coated
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61Q 11/00 : Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• CPC Class Codes: C07D 279/18 : [b, e]-condensed with two six-membered rings

Abstract

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 R¹, R², R³ and R⁴ each independently is an optionally -substituted linear, branched or cyclic hydrocarbon group, or R¹ and R² together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7- membered ring or R³ and R⁴ 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 —NR¹R² and —NR³R⁴ are the same and are selected from —N(CH₃)₂ or —N(CH₂CH₃)₂; and
  • exposing the area to light to activate the compound.

Claims

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

2. A method as claimed in claim 1, wherein in said compound R¹, R², R³, and R⁴ are the same and are selected from n-propyl, n-butyl, and n-pentyl.

3. A method as claimed in claim 1, wherein R¹ , R², R³ and R⁴ each represent n-pentyl.

4. A method as claimed in claim 1, wherein R¹, R², R³ and R⁴ each represent n-pentyl and X^P−

represents Cl⁻

, Br⁻

, I⁻

, F⁻

, NO₃⁻

, HSO₄⁻

, CH₃CO₂⁻

or a dianion namely SO₄²⁻

or H₂PO₄²⁻

.

5. A method as claimed in claim 1, wherein R¹, R², R³ and R⁴ each represent n-butyl.

6. A method according to claim 1, wherein X^P−

is selected from F⁻

, Br⁻

, Cl⁻

, I⁻

, NO₃⁻

, SCN⁻

, ClO₃⁻

, ClO₄⁻

, IO₃⁻

, BF₄⁻

, HSO₄⁻

, H₂PO₄⁻

, CH₃SO₄⁻

, N₃⁻

, SO₄²⁻

, HPO₄²⁻

, PO₄³⁻

, 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 R¹, R², R³ and R⁴ 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.