Compositions and methods for the treatment of metabolic bone disorders and bone metastases
First Claim
1. A pharmaceutical composition comprising a photosensitizer agent conjugated to a compound selected from the group consisting of:
- bisphosphonates;
pyrophosphonates;
thiobisphosphonates; and
nitrobisphosphonates.
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Accused Products
Abstract
Methods and compositions useful for targeting and treating target tissues affected by or involved in metabolic bone disorders and bone metastases with photodynamic therapy (PDT) in a mammalian subject are provided. The compositions are biphosphonates, pyrophosphates, or biphosphonate-like compounds conjugated to photosensitive agents which are optionally further conjugated to ligands which are target tissue specific antibodies, peptides, or polymers. The method of PDT treatment utilize these compositions to target the tissues or cells of a mammalian subject to be treated. The methods include irradiating at least a portion of the subject with light at a wavelength absorbed by said photosensitizing agent that under conditions of activation during photodynamic therapy using a relatively low fluence rate, but an overall high total fluence dose results in minimal collateral tissue damage.
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Citations
24 Claims
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1. A pharmaceutical composition comprising a photosensitizer agent conjugated to a compound selected from the group consisting of:
- bisphosphonates;
pyrophosphonates;
thiobisphosphonates; and
nitrobisphosphonates. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 17, 18, 19, 22, 23, 24)
- bisphosphonates;
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13. A method for destroying or impairing target cells involved in disease of bone tissue in a mammalian subject comprising:
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administering to the subject a therapeutically effective amount of a composition comprising a photosensitizer agent conjugated to a compound selected from the group consisting of;
bisphosphonates;
pyrophosphonates;
thiobisphosphonates; and
nitrobisphosphonates, wherein said composition selectively binds the target cells or target tissues involved in said disease of bone tissue; and
irradiating at least a portion of the subject with light at a wavelength absorbed by said composition, wherein said light is provided by a light source, and wherein said irradiation is at a relatively low fluence rate that results in the activation of said composition, wherein said composition is cleared from non-target tissues of the subject prior to said irradiation.
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15. A method for treating a metabolic bone disorder or bone metastases in a mammalian subject comprising:
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administering to the subject a therapeutically effective amount of a composition comprising a photosensitizer agent selected from the group consisting of chlorins, bacteriochlorins, phthalocyanines, porphyrins, purpurins, merocyanines, psoralens, benzoporphyrin derivatives (BPD), porfimer sodium, delta-aminolevulinic acid, protoporphyrin, indocyanine green (ICG), methylene blue, toluidine blue, texaphyrins and any other agent that absorbs light in a range of 500 nm-1100 nm which is conjugated to a compound selected from the group consisting of;
bisphosphonates;
pyrophosphonates;
thiobisphosphonates; and
nitrobisphosphonates which selectively binds the target tissues or cells involved in the metabolic bone disorder or bone metastases and said composition is further conjugated to an imaging agent; and
performing a nuclear medicine scan;
imaging the target tissues or cells to be treated; and
irradiating at least a portion of the subject with light at a wavelength absorbed by said composition, wherein said light is provided by a light source, and wherein said irradiation is at a relatively low fluence rate that results in the activation of said composition, wherein said composition is cleared from non-target tissues of the subject prior to said irradiation.
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20. A method for destroying or impairing target cells involved in disease of bone tissue in a mammalian subject comprising:
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administering to the subject a therapeutically effective amount of a composition comprising a photosensitizer agent, wherein said agent is selected from the group consisting of chlorins, bacteriochlorins, phthalocyanines, porphyrins, purpurins, merocyanines, psoralens, benzoporphyrin derivatives (BPD), porfimer sodium, delta-aminolevulinic acid, protoporphyrin, indocyanine green (ICG), methylene blue, toluidine blue, texaphyrins and any other agent that absorbs light in a range of 600 nm-1100 nm, and wherein said agent is conjugated to a compound selected from the group consisting of;
bisphosphonates;
pyrophosphonates;
thiobisphosphonates; and
nitrobisphosphonates; and
wherein said composition selectively binds the target cells or target tissues involved in said disease of bone tissue; and
irradiating at least a portion of the subject with light at a wavelength absorbed by said composition, wherein said light is provided by a light source, and wherein said irradiation is at a relatively low fluence rate that results in the activation of said composition; and
wherein said composition is cleared from non-target cells or non-target tissues of the subject prior to said irradiation. - View Dependent Claims (21)
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Specification