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Method for determining condition parameters for photodynamic therapy and photodynamic therapy apparatus

A technology of photodynamic therapy and conditional parameters, applied in the fields of phototherapy, radiotherapy, treatment, etc., can solve the strict relationship between the energy density of light irradiation and the cytocidal effect, the undisclosed amount of PpIX accumulation and the relationship between the energy density of light irradiation and the cytotoxic effect. Strict relationship of cytocidal effect etc.

Pending Publication Date: 2021-09-28
OTSUKA DENSHI CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] As mentioned above, these tendencies are known to be dependent on each other. On the other hand, the strict relationship between the accumulation of PpIX in cells and the energy density of light irradiation in PDT and the cytocidal effect has not yet been clarified.
In addition, regarding the dependency relationship between these and the cytocidal effect when the type, source, and primary disease of the target cell are different, the correlation and similarity beyond the type, source, etc. of the target cell are not known at all.
[0006] In addition, although Patent Documents 3 and 4 and Non-Patent Document 1 also refer to PDT, they do not disclose any strict relationship between intracellular PpIX accumulation and light irradiation energy density and cytocidal effect in PDT.

Method used

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  • Method for determining condition parameters for photodynamic therapy and photodynamic therapy apparatus
  • Method for determining condition parameters for photodynamic therapy and photodynamic therapy apparatus
  • Method for determining condition parameters for photodynamic therapy and photodynamic therapy apparatus

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Embodiment 1

[0065] Using four cell lines (ATN-1, TL-Om1, HuT102, and MT-1) from human adult T-cell leukemia (ATL) and one HTLV-1 transformed (transform) cell line (C8166), through HPLC The amount of protoporphyrin IX (PpIX) accumulated in cells due to 5-ALA loading (0, 0.0625, 0.125, 0.25, and 0.5 mmol / L) was measured by chromatographic fluorescence detection as a cytocidal assay using PDT for all The cells were irradiated with light with a central wavelength of 630nm (10, 30 and 100J / cm 2 ), calculate the cell viability (%) based on the cell number assay kit Cell Counting Kit-8. For the results of all cell lines, according to each light irradiation energy density, the cell survival rate was plotted on the vertical axis, and the intracellular PpIX accumulation was plotted on the horizontal axis, and the regression analysis was implemented by the statistical analysis software SAS software Release9.3 ( image 3 ). As a result, the four-parameter logistic model (Table 1) was converged at a...

Embodiment 2

[0071] For Jurkat cells (human acute lymphoblastic leukemia cells) from human T-cell leukemia, which has a different disease classification from human adult T-cell leukemia, 5-ALA load (0, 0.0625, 0.125 , 0.25, 0.5 and 1mmol / L) and the amount of protoporphyrin IX accumulated in the cell, and then as a cytocidal test utilizing PDT, light irradiation with a central wavelength of 630nm (30J / cm 2 ), calculate the cell viability (%) based on the cell number assay kit CellCounting Kit-8. As a result, cell viability lies at image 3 On the regression curves recorded, it was proved that this relationship was strictly established even in leukemias with different disease classifications ( Figure 4 ).

Embodiment 3

[0073] (a way of clinical use)

[0074] After a cancer patient takes 5-ALAs, the amount of PpIX accumulated in the patient's cancer cells is measured (X), and the amount of PpIX accumulated in the cell and the therapeutic target value of the cytocidal effect (corresponding to the cell survival rate (Y)) Input to photodynamic therapy device. According to the input value, the photodynamic therapy device refers to the pre-programmed regression curve or a look-up table with a stepwise range derived from the regression curve to determine the light irradiation energy density (P) corresponding to the treatment target value, and implement the treatment. In this case, the intracellular accumulation of PpIX, the therapeutic target value of cytocidal effect, and the energy density of light irradiation may be continuous values ​​or stepwise values.

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Abstract

The present invention is a method for determining condition parameters for photodynamic therapy in which protoporphyrin IX accumulated within cells is irradiated with light after administration of 5-aminolevulinic acid to a subject. The method comprises the steps of calculating a regression curve representing a correlation between three condition parameters of the cell survival (Y), the amount (X) of protoporphyrin IX accumulated within cells, and the light irradiation energy density (P) in an experimental stage; and preliminarily selecting two condition parameters from among the cell survival (Y), the amount (X) of protoporphyrin IX accumulated within cells, and the light irradiation energy density (P) before the start of treatment, and determining the remaining condition parameter by using the regression curve. The photodynamic therapy can be optimized by such a technique.

Description

technical field [0001] The present invention relates to photodynamic therapy using 5-aminolevulinic acid. Background technique [0002] Photodynamic therapy (photodynamic therapy: PDT) refers to the following treatment method, that is, administering a photosensitive substance or its precursor to make it accumulate in tumor tissue, new blood vessels, skin surface, etc. Irradiating light with an absorption wavelength as excitation light utilizes the cell-killing effect of active oxygen species including singlet oxygen generated by excitation. [0003] 5-Aminolevulinic acid (5-ALA) is an orally absorbable substance that is metabolized into protoporphyrin IX (PpIX) during the biosynthesis of heme in the mitochondria in cells. PpIX is a photosensitive substance that has an absorption band around 410nm called the Soret band and an absorption band around 500-650nm called the Q band, and generates active oxygen species by irradiating light with wavelengths in these absorption bands...

Claims

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Application Information

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IPC IPC(8): A61N5/06
CPCA61N5/062G16H20/40G16H50/20A61P35/02A61K41/0061A61K41/0071A61N2005/0626A61N2005/0663G01N33/5011
Inventor 小桥真之太田和秀原田康男
Owner OTSUKA DENSHI CO LTD
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