Uses of porphyrin compounds
Inventors
Love, William G. • Rhys-Williams, William • Brundish, Derek
Assignees
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Publication Number
US-7977474-B2
Publication Date
2011-07-12
Expiration Date
Abstract
The invention provides the use of a compound of Formula (I), or metallated derivative thereof, in the preparation of a medicament for killing or attenuating the growth of microorganisms by a method which does not comprise exposing the compound to a photodynamic therapy light source or a sonodynamic therapy ultrasound source Formula (I) wherein X1, X2, X3, X4, Yi, Y2, Y3, Y4 and Z have meanings given in the description. Preferably, the microorganisms are selected from the group consisting off bacteria, mycoplasmas, yeasts, fungi and viruses.
Core Innovation
Porphyrin-based medicaments are disclosed for killing microorganisms or attenuating microbial growth using compounds of Formula (I) or Formula (II), including metallated derivatives. The disclosed porphyrin compounds include quaternary ammonium and other cationic structures such that antimicrobial activity is intrinsic to the compound, and the method avoids exposing the compound to a stimulus that activates antimicrobial activity.
The disclosure states that antimicrobial activity is not activated by light exposure for photodynamic therapy or ultrasound exposure for sonodynamic therapy. This framing supports antimicrobial action at locations that may be light-inaccessible and addresses limitations of conventional photodynamic therapy, including host toxicity, low potency, and the need for light-accessible sites.
Formula (I)/(II) is defined with substituent options including cationic groups of the form L-R1-N+(R2)(R3)R4 with a linking moiety L, optional metallic element or metalloid center M, and a Z group selected from —CH or N. Additional substituent variables include optional pyrrole substituents Y1–Y4 and substituent sets X1–X4 that are independently hydrogen, lipophilic moiety, phenyl, lower alkyl, alkaryl, aralkyl, or a cationic group, with at least one cationic group and at least one hydrogen atom.
Claims Coverage
The partial content provides independent claim clm-00001 and independent claims clm-00059 and clm-00060. Across these independent claims, the main inventive elements are administering a compound of Formula (I) or (II) with antimicrobial activity not activated by a stimulus, avoiding specific activating stimuli, and constraining the lipophilic moiety chain-length parameter p to numeric ranges in later independent claims.
Administering a Formula I or II compound with antimicrobial activity not activated by a stimulus
A method for killing microorganisms comprising administering to a patient an effective amount of a compound of Formula I or II, wherein the compound of formula I or II is not exposed to a stimulus which activates antimicrobial activity, and wherein at least one of X1, X2, X3 and X4 is a cationic group and at least one of X1, X2, X3 and X4 is a hydrogen atom.
Avoiding stimulus activation by photodynamic therapy light or ultrasound
The method further defines that antimicrobial activity is not activated by avoiding exposure to irradiation with a photodynamic therapy light source or an ultrasound source.
Lipophilic moiety chain-length parameter p between 2 and 16
A method wherein p is between 2 and 16.
Lipophilic moiety chain-length parameter p between 4 and 12
A method wherein p is between 4 and 12.
The independent claim set centers on administering Formula (I)/(II) porphyrin compounds engineered to have intrinsic antimicrobial activity without stimulus activation, and it constrains later variants by restricting the lipophilic moiety chain-length parameter p to defined ranges.
Stated Advantages
Innate antibacterial activity without light.
Low MIC/MBC values against multiple gram-positive strains and clinical isolates.
Lack of toxicity in human keratinocytes and fibroblasts.
Chemical stability in stressed solid/solution conditions and formulations.
No observed acute effects in acute dermal toxicity testing.
Provides killing microorganisms using porphyrin compounds with intrinsic antimicrobial activity.
Avoids activation of antimicrobial activity by a stimulus, including avoiding photodynamic therapy light and ultrasound exposure.
Addresses limitations of conventional photodynamic therapy by enabling antimicrobial action without requiring light-accessible sites.
Claims aim to avoid host toxicity and address low potency issues associated with conventional approaches (as described in the background).
Documented Applications
Use in a method for killing microorganisms by administering an effective amount of a compound of Formula I or II to a patient.
Prophylactic and curative treatment of infections by microorganisms including bacteria, mycoplasmas, yeasts, fungi, and viruses, including infections at light-inaccessible sites.
Treatment scope includes applications where avoiding photodynamic therapy light source or ultrasound source activation is relevant (as described for the method and dependently specified conditions).
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