METHOD AND DEVICE FOR PHOTODYNAMIC THERAPY

• US 20090204057A1
• Filed: 07/17/2007
• Published: 08/13/2009
• Est. Priority Date: 07/24/2006
• Status: Active Grant

• Current Assignee: Quest PharmaTech, Inc.
• Original Assignee: Quest PharmaTech, Inc.
• Inventors: Miller, Gerald George, Woo, Thomas, Madiyalakan, Ragupathy
• Granted Patent: US 8,454,991 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61K 2800/434 Luminescent, Fluorescent; Optical brighteners; Photosensitizers
• 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 8/355 Quinones
• CPC Class Codes: A61K 8/415 Aminophenols
• CPC Class Codes: A61N 2005/0645 Applicators worn by the patient
• CPC Class Codes: A61N 2005/0651 Diodes
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: A61Q 9/04 Depilatories
• CPC Class Codes: C09K 11/07 having chemically interreactive components, e.g. reactive chemiluminescent compositions

Abstract

The present invention relates to a photodynamic therapy method and uses thereof for treating an individual in need thereof, comprising administering a photosensitizer to an individual and activating the photosensitizer with a chemiluminescent light source, and/or a light-emitting diode light source, wherein the light source is in dermal contact with the individual. The present invention also relates to a device for photodynamic therapy comprising a permeable reservoir, for containing a photosensitizer formulation for skin application, the device is adapted to deliver the photosensitizer to the individual. The present invention also relates to a device for photodynamic therapy, comprising a permeable reservoir for containing a photosensitizer formulation for skin application and a light source. The light source is a chemiluminescent light source or a light-emitting diode light source and the device is adapted to deliver the photosensitizer to the individual and to irradiate a part of an individual to activate the photosensitizer.

Claims

1. A photodynamic therapy method for treating a subject in need thereof comprising:

a) administering a photosensitizer to the subject and

b) activating said photosensitizer with a chemiluminescent light source.

2. The method as claimed in claim 1 wherein said chemiluminescent light source is comprised in a device comprising a permeable reservoir for containing a photosensitizer formulation for skin application, adjacent to the chemiluminescent light source;

wherein said device is adapted to deliver said photosensitizer to said subject and to irradiate a part of said subject to activate said photosensitizer.

3. The method as claimed in claim 2 wherein said device is a dermal patch.

4. The method of claim 1, wherein said chemiluminescent light source is from. chemiluminescent reaction between a chemiluminescent reaction catalyst and a fluorophore, wherein said fluorophore absorbs and reemits energy as light.

5. The method of claim 4, wherein said fluorophore is 9,10-diphenylanthracene, 9,10-bis(phenylethynyl)anthracene, 1-chloro-9,10-bis(phenylethynyl)anthracene, rubrene, 5,12-bis(phenylethynyl)-naphthacene, rhodamine 6, or rhodamine B.

6. The method of claim 4, wherein said chemiluminescent reaction catalyst is hydrogen peroxide.

7. The method of claim 1, wherein the photosensitizer is at least one selected from the group consisting of hypocrellin B and its functional derivatives, fluoresceins, indocyanine green, rhodamine, triphenylamines, polymethines, cyanines, phthalocyanines, naphthocyanines, merocyanines, fullerenes, oxatellurazoles, verdins, rhodins, perphycenes, sapphyrins, rubyrins, metalloporphyrins, cholesteryl 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoate, cholesteryl 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-dodecanate, cholesteryl cis-parinarate, cholesteryl 3-((6-phenyl)-1,3,5-hexatrienyl)phenylproprionate, cholesteryl 1-pyrenebutyrate, cholesteryl 1-pyrenedecanoate, cholesteryl 1-pyrenehexanoate, 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β

-ol, 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β

-yl cis-9-octadecenoate, 1-pyrenemethyl 3-(hydroxy-22,23-bisnor-5-cholenate, 1-pyrenemethyl 3β

-(cis-9-octadecenoyloxy)-22,23-bisnor-5-cholenate, acridine orange 10-dodecyl bromide, acridine orange 10-nonyl bromide, 4-(N,N-dimethyl-N-tetradecylammonium)methyl-7-hydroxycoumarin) chloride, 2-dodecylresorufin, 4-heptadecyl-7-hydroxycoumarin, 5-hexadecanoyl-aminoeosin, N-octadecyl-N′

-(5-(fluoresceinyl))-thiourea, octadecyl rhodamine B chloride, 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine, 6-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoic acid, 1-hexadecanoyl-2-(1-pyrenedecanoyl)-sn-glycero-3-phosphocholine, 1,1′

-dioctadecyl-3,3,3′

,3′

-tetramethylindocarbocyanine perchlorate, 12-(9-anthroyloxy)oleic acid, 5-butyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-3-nonanoic acid, N-(lissamine rhodamine B sulfonyl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt, phenylglyoxal monohydrate, naphthalene-2,3-dicarbox-aldehyde, 8-bromomethyl-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene, o-phthaldialdehyde, lissamine rhodamine B sulfonyl chloride, 9-anthronitrile, 1-pyrenesulfonyl chloride, 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide, texaphyrins, texaphyrin-metal chelates, chlorins, chlorin e6, bonellin, mono-L-aspartylchlorine6, mesochlorin, mesotetraphenylisobacteriochlorin, mesotetraphenyl-bacteriochlorin, hypocrellin B, purpurins, octaethylpurpurin, zinc(II) etiopurpurin, tin(IV) etiopurpurin, tin ethyl etiopurpurin, lutetium texaphyrin, photofrin, protoporphyrin IX, tin protoporphyrin, porphyrins, benzoporphyrins, haematoporphyrin, methylpheophorbide-α

-(hexyl-ether), porphycenes, ketochlorins, sulfonated tetraphenylporphines, chlorophyll, carotenoids, flavonoids, bilins, phytochromes, phycobilins, phycoerythrin, phycocyanines, retinoic acid, retinoins and retinates.

8. The method of claim 1, wherein the photosensitizer is at least one selected from the group consisting of a compound of formula (Ia) or (Ib) or stereoisomer

wherein

X and Y are independently hydrogen, C₁-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aryl, C₆-C₁₂ aralkyl, C₁-C₁₂ heterocyclyl, C₁-C₁₂ heteroaryl, —

COR₁, —

(CH₂)_mOR₁, —

CO₂H, —

CO₂R₁, —

C(O)N(R₁)₂, —

C(O)NH(R₁), or —

C(O)NH₂,

said C₁-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aryl, C₆-C₁₂ aralkyl, C₁-C₁₂ heterocyclyl, and C₁-C₁₂ heteroaryl being unsubstituted or substituted with at least one substituent selected from the group consisting of a halogen atom, hydroxy, carboxy, thiol, azide, nitro, C₁-C₈ deuterated alkyl group comprising at least one deuterated atom, —

COH, —

COR₁, —

(CH₂)_mOR₁, —

CO₂H, —

CO₂R₁, —

C(O)N(R₁)₂—

C(O)NH(R₁), —

C(O)NH₂, C₁-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aryl, C₆-C₁₂ aralkyl, C₁-C₁₂ heterocyclyl, and C₁-C₁₂ heteroaryl;

Z is —

CH₂—

, —

CHR₃—

, —

CH₂—

CH═

CH—

, —

CHR₃—

CH═

CH—

, or —

CH₂—

CH═

CR₃—

;

R₁ is a hydrogen atom, C₁-C₈ alkyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aralkyl, or C₁-C₁₂ heterocyclyl;

each R₂ is independently a hydrogen atom, C₁-C₈ alkyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aralkyl, or C₁-C₁₂ heterocyclyl;

R₃ is halogen atom, hydroxy, sulphydral (—

SH), an amino acid residue, carboxy, thiol, azide, nitro, SO₃H, —

COH, —

COR₁, —

(CH₂)_mOR₁, —

CO₂H, —

CO₂R₁, —

C(O)N(R₁)₂—

C(O)NH(R₁), —

C(O)NH₂, —

HNC(O)R₁, C₁-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aryl, C₆-C₁₂ aralkyl, C₁-C₁₂ heterocyclyl, or C₁-C₁₂ heteroaryl;

n is an integer having a value of 1 to 13; and

m is an integer having a value of 1 to 13;

of and any pharmaceutically acceptable salt thereof.

9. A device for photodynamic therapy comprising:

a first permeable reservoir, for containing a photosensitizer formulation for topical application on a subject for activation by light.

10. The device as claimed in claim 9, which is a dermal patch.

11. The device as claimed in claim 9, further comprising a skin-contacting layer, located between the first permeable reservoir and the skin, which comprises a soothing element and/or a topical desensitizing agent.

12. The device as claimed in claim 9, wherein said first permeable reservoir is for further containing a topical desensitizing agent.

13. The device as claimed claim 9, further comprising a chemiluminescent light source to activate said photosensitizer in situ.

14. The device as claimed in claim 13, wherein said chemiluminescent light source is to be located substantially over said first reservoir, to activate said photosensitizer in situ.

15. The device as claimed in claim 13 further comprising a second reservoir having an outer membrane with an inner reflective surface and containing reactants in separate compartments;

wherein separation of said compartments is disrupted to cause a chemical reaction to generate chemiluminescence.

16. The device of claim 9, wherein said chemiluminescent light source is from a chemiluminescent reaction between a chemiluminescent reaction catalyst and a fluorophore, wherein said fluorophore absorbs and reemits energy as light.

17. The device of claim 16, wherein said fluorophore is 9,10-diphenylanthracene, 9,10-bis(phenylethynyl)anthracene, 1-chloro-9,10-bis(phenylethynyl)anthracene, rubrene, 5,12-bis(phenylethynyl)-naphthacene, rhodamine 6G or rhodamine B.

18. The device of claim 15, wherein said chemiluminescent reaction catalyst is hydrogen peroxide.

19. The device of claim 9, wherein the photosensitizer is at least one selected from the group consisting of hypocrellin B and its functional derivatives, fluoresceins, indocyanine green, rhodamine, triphenylamines, polymethines, cyanines, phthalocyanines, naphthocyanines, merocyanines, fullerenes, oxatellurazoles, verdins, rhodins, perphycenes, sapphyrins, rubyrins, metalloporphyrins, cholesteryl 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoate, cholesteryl 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-dodecanate, cholesteryl cis-parinarate, cholesteryl 3-((6-phenyl)-1,3,5-hexatrienyl)phenylproprionate, cholesteryl 1-pyrenebutyrate, cholesteryl 1-pyrenedecanoate, cholesteryl 1-pyrenehexanoate, 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β

-ol, 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β

-yl cis-9-octadecenoate, 1-pyrenemethyl 3-(hydroxy-22,23-bisnor-5-cholenate, 1-pyrenemethyl 3β

-(cis-9-octadecenoyloxy)-22,23-bisnor-5-cholenate, acridine orange 10-dodecyl bromide, acridine orange 10-nonyl bromide, 4-(N,N-dimethyl-N-tetradecylammonium)methyl-7-hydroxycoumarin) chloride, 2-dodecylresorufin, 4-heptadecyl-7-hydroxycoumarin, 5-hexadecanoyl-aminoeosin, N-octadecyl-N′

-(5-(fluoresceinyl))-thiourea, octadecyl rhodamine B chloride, 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine, 6-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoic acid, 1-hexadecanoyl-2-(1-pyrenedecanoyl)-sn-glycero-3-phosphocholine, 1,1′

-dioctadecyl-3,3,3′

,3′

-tetramethylindocarbocyanine perchlorate, 12-(9-anthroyloxy)oleic acid, 5-butyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-3-nonanoic acid, N-(lissamine rhodamine B sulfonyl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt, phenylglyoxal monohydrate, naphthalene-2,3-dicarbox-aldehyde, 8-bromomethyl-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene, o-phthaldialdehyde, lissamine rhodamine B sulfonyl chloride, 9-anthronitrile, 1-pyrenesulfonyl chloride, 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide, texaphyrins, texaphyrin-metal chelates, chlorins, chlorin e6, bonellin, mono-L-aspartylchlorine6, mesochlorin, mesotetraphenylisobacteriochlorin, mesotetraphenyl-bacteriochlorin, hypocrellin B, purpurins, octaethylpurpurin, zinc(II) etiopurpurin, tin(IV) etiopurpurin, tin ethyl etiopurpurin, lutetium texaphyrin, photofrin, protoporphyrin IX, tin protoporphyrin, porphyrins, benzoporphyrins, haematoporphyrin, methylpheophorbide-α

-(hexyl-ether), porphycenes, ketochlorins, sulfonated tetraphenylporphines, chlorophyll, carotenoids, flavonoids, bilins, phytochromes, phycobilins, phycoerythrin, phycocyanines, retinoic acid, retinoins and retinates.

20. The device of claim 9, wherein the photosensitizer is at least one selected from the group consisting of a compound of formula (Ia) or (Ib) or stereoisomer or atropisomer thereof:

wherein

X and Y are independently hydrogen, C₁-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aryl, C₆-C₁₂ aralkyl, C₁-C₁₂ heterocyclyl, C₁-C₁₂ heteroaryl, —

COR₁, —

(CH₂)_mOR₁, —

CO₂H, —

CO₂R₁, —

C(O)N(R₁)₂, —

C(O)NH(R₁), or —

C(O)NH₂,

said C₁-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aryl, C₆-C₁₂ aralkyl, C₁-C₁₂ heterocyclyl, and C₁-C₁₂ heteroaryl being unsubstituted or substituted with at least one substituent selected from the group consisting of a halogen atom, hydroxy, carboxy, thiol, azide, nitro, C₁-C₈ deuterated alkyl group comprising at least one deuterated atom, —

COH, —

COR₁, —

(CH₂)_mOR₁, —

CO₂H, —

CO₂R₁, —

C(O)N(R₁)₂—

C(O)NH(R₁), —

C(O)NH₂, C₁-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aryl, C₆-C₁₂ aralkyl, C₁-C₁₂ heterocyclyl, and C₁-C₁₂ heteroaryl;

Z is —

CH₂—

, —

CHR₃—

, —

CH₂—

CH═

CH—

, —

CHR₃—

CH═

CH—

, or —

CH₂—

CH═

CR₃—

;

R₁ is a hydrogen atom, C₁-C₈ alkyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aralkyl, or C₁-C₁₂ heterocyclyl;

each R₂ is independently a hydrogen atom, C₁-C₈ alkyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aralkyl, or C₁-C₁₂ heterocyclyl;

R₃ is halogen atom, hydroxy, sulphydral (—

SH), an amino acid residue, carboxy, thiol, azide, nitro, SO₃H, —

COH, —

COR₁, —

(CH₂)_mOR₁, —

CO₂H, —

CO₂R₁, —

C(O)N(R₁)₂—

C(O)NH(R₁), —

C(O)NH₂, —

HNC(O)R₁, C₁-C₈ alkyl, C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkenyl, C₆-C₁₂ aryl, C₆-C₁₂ aralkyl, C₁-C₁₂ heterocyclyl, or C₁-C₁₂ heteroaryl;

n is an integer having a value of 1 to 13; and

m is an integer having a value of 1 to 13;

and any pharmaceutically acceptable salt thereof.