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Publication Number
US-11607455-B2
Publication Date
2023-03-21
Expiration Date
Abstract
Methods for treating cancer and/or inducing tumor regression in mammals (e.g., humans) by increasing the metabolism of the mammal, administering a BA dye to the mammal, and thereafter exposing the tumor to actinic light for activation of the BA dye.
Core Innovation
The invention provides a method of treating pancreatic cancer in a subject by administering at least one of glucose, glucagon, corticosteroids, growth hormones, thyroid hormones and insulin until the plasma glucose level of the subject is above the basal plasma glucose of the subject, then administering at least one EtNBS compound, and finally exposing the subject to actinic light.
The approach is described as a counterintuitive cancer and BA-PDT regimen in which metabolism is first increased to a level above basal, after which a BA photosensitizer is administered and actinic light is applied. The description characterizes the actinic exposure by a BA T_max window and a low post-T_max plasma fraction to support the photodynamic effect.
The disclosed regimen is further described as synergistically improving BA-PDT tumor regression or eradication rates in multiple animal models, including pancreatic, bladder, and glioma. The description also states that enhancement can be obtained by circadian neuroendocrine resetting therapy using bromocriptine and prolactin timed to waking and sleep rhythms.
Claims Coverage
The partial content includes one independent claim directed to treating pancreatic cancer in a subject with a sequence of metabolism-related administration, EtNBS administration, and exposure to actinic light. Dependent claims refine aspects of metabolism elevation, EtNBS identity, actinic light wavelength/energy, and EtNBS plasma timing criteria.
Raising plasma glucose above basal with metabolism-related agents
Administering at least one of glucose, glucagon, corticosteroids, growth hormones, thyroid hormones and insulin to the subject until the plasma glucose level of the subject is above the basal plasma glucose of the subject.
Administering an EtNBS compound
Administering at least one EtNBS compound to the subject.
Exposing the subject to actinic light
Exposing the subject to actinic light.
Quantitative plasma glucose elevation threshold
The method includes increasing a subject’s plasma glucose level by at least a specified percentage above its basal plasma glucose level.
Specific EtNBS compound identity
The method is carried out using the specific EtNBS compound 2-iodo-5-ethylamino-9-diethylamino-benzophenothiazinium chloride.
Wavelength-constrained actinic light exposure
The method uses actinic light having a wavelength range of 600-700 nm.
Total light energy constrained actinic exposure
The method is carried out such that actinic light delivers a total light energy of between about 50 and about 500 Joules per square centimeter.
EtNBS Tmax timing window
The method includes administering an EtNBS compound at a rate that produces a plasma EtNBS Tmax of BA within about 10 to 240 minutes.
Overall, the claim set centers on sequential treatment of pancreatic cancer using metabolism-related agents to raise plasma glucose above basal, followed by administration of an EtNBS compound and exposure to actinic light. Dependent refinements constrain the extent of glucose elevation, specify an EtNBS compound identity, constrain actinic light wavelength and total energy, and define an EtNBS plasma Tmax timing window.
Stated Advantages
Synergistically improves BA-PDT tumor regression/eradication rates in multiple animal models (pancreatic, bladder, glioma).
Documented Applications
Treating pancreatic cancer in a subject using a BA-PDT regimen that includes raising plasma glucose above basal, administering an EtNBS compound, and exposing the subject to actinic light.
Circadian neuroendocrine resetting therapy enhancement using bromocriptine and prolactin timed to waking and sleep rhythms in the disclosed regimen.
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