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Photosensitizer conjugates for pathogen targeting

A technology of conjugates and photosensitizers, applied in antiviral agents, drug combinations, medical preparations containing active ingredients, etc.

Inactive Publication Date: 2000-05-31
THE GENERAL HOSPITAL CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Current treatments often rely on mechanical removal of plaque and bacteria, which may not be effective (Unsal E. et al. (1995), J. periodontol. 66:47-51), or on antibiotic therapy, This way can lead to bacterial resistance (Olsvik, B. et al (1995) J. Clin. Periodontol.) 22: 391-396)

Method used

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  • Photosensitizer conjugates for pathogen targeting
  • Photosensitizer conjugates for pathogen targeting
  • Photosensitizer conjugates for pathogen targeting

Examples

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preparation example Construction

[0211] Oligonucleotide-mediated mutagenesis is a useful method for making DNA substitution, deletion or insertion variants (see eg Adelma et al., DNA 2:183, 1983). Briefly, the desired DNA is altered by hybridizing a mutation-encoding oligonucleotide to a DNA template, where the template is a single-stranded form of a plasmid or an unaltered or wild-type DNA sequence containing the desired protein. Phage type DNA sequence. After hybridization a DNA polymerase is used to synthesize the complete second complementary strand of the template so that the template is thus incorporated into the oligonucleotide primer and encodes the selected alteration in the desired protein DNA. Typically, oligonucleotides of at least 25 nucleotides in length are used. Optimal oligonucleotides have 12-15 nucleotides and are perfectly complementary to the sequence on the template flanking the mutation-encoding nucleotides. This ensures proper hybridization of the oligonucleotide to the single-strand...

Embodiment 5

[0262] Such as image 3 and 4 As shown, the absorption of the conjugate is a function of concentration, where image 3 and 4 Represent Porphyromonas gingivalis and HCPC-1 cells respectively (the vertical axis of the figure differs by 50 times). The absorption of chlorin e6 is dose-dependent. The cellular accumulation of cationic conjugates in P. gingivalis and HCPC-1 cells was 2 and 2-4 times more than that of anionic and neutral conjugates at each concentration, respectively. It was observed that photosensitizer conjugates accumulated more selectively in bacteria than in mammals. Photodamage of embodiment 5 chlorin e6

[0263] To establish the effectiveness and selectivity of these conjugates in killing bacteria while retaining mammalian cells, three conjugates and two widely used clinical photosensitizers - Photofrin II and benzoporphyrin derivatives (BPD) (QLT Phototherapeutics Inc, Vancouver BC) for comparison. The photosensitizer bulk solid was dissolved in 1 mM DM...

Embodiment 6

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Abstract

Conjugate molecules which include photosensitizer compositions conjugated to non-antibody non-affinity pair targeting moieties and methods of making and using such conjugates are aslo described.

Description

field of invention [0001] The present invention relates to conjugates comprising a photosensitizer and a targeting moiety, and methods of using the conjugates. Background of the invention [0002] Infectious diseases remain an unresolved problem, mainly due to the emergence of multiantimicrobial-resistant bacterial strains, newly discovered viral diseases, and the spread of fungal and protozoan diseases. [0003] Advanced periodontal disease is one of many oral infections and is the leading cause of tooth loss in patients over the age of 30. Periodontal disease is caused by the interaction between bacterial cells and their products in dental plaque and host defense mechanisms (Antczak-Bouckoms, A (1994), J. Dent. Educ. 58:625-640). Current treatments often rely on mechanical removal of plaque and bacteria, which may not be effective (Unsal E. et al. (1995), J. periodontol. 66:47-51), or on antibiotic therapy, This approach can lead to bacterial resistance (Olsvik, B. et al...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/409A61K38/00A61K41/00A61P1/02A61P31/04
CPCA61K41/0019A61K41/17A61P1/02A61P31/00A61P31/04A61P31/12A61P33/00A61P33/02A61K31/555
Inventor 塔耶巴·汉森迈克尔·R·汉布林马科斯·苏科斯
Owner THE GENERAL HOSPITAL CORP