DYNAMIC COLORECTAL PDT APPLICATION

• US 20120259187A1
• Filed: 01/24/2012
• Published: 10/11/2012
• Est. Priority Date: 01/24/2011
• Status: Active Grant

• Current Assignee: Biolitec Unternehmensbeteiligungs II AG
• Original Assignee: CeramOptec Industries Incorporated (Biolitec AG)
• Inventors: Amelink, Arjen, Neuberger, Wolfgang, Kruijt, Bastiaan, van der Snoek, Eric M., Sterenborg, Henricus J.C.M., Robinson, Dominic J.
• Granted Patent: US 9,034,023 B2
• Time in Patent Office: Days
• US Class Current: 600/317
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/4255 Intestines, colon or appendix
• CPC Class Codes: A61K 31/409 having four such rings, e.g. porphine derivatives, bilirubin, biliverdine hemin, hematin A61K31/555
• CPC Class Codes: A61N 2005/0608 Rectum
• CPC Class Codes: A61N 2005/0628 including a radiation sensor
• CPC Class Codes: A61N 2005/063 comprising light transmitting means, e.g. optical fibres
• CPC Class Codes: A61N 2005/0662 Visible light
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Dynamic colorectal PDT methods, devices and photosensitizer compositions to treat abnormal cell growth in anal tissue such as perianal and intra-anal intraepithelial neoplasia grade III are presented. Dynamic colorectal PDT method comprises the steps of administering topically, intravenously or orally a photosensitizer composition; irradiating; monitoring treatment parameters before, during and/or after irradiation. Photosensitizer composition comprises Temoporfin and excipients/carriers, appropriate for the application method. An applicator is provided for colorectal PDT treatments enhancing irradiation delivery and monitoring treatment parameters. Preferably, applicator is made of a material, used to monitor the fluence rate simultaneously while doing optical spectroscopy. Measurement probe devices are provided for monitoring PDT treatment parameters in-vivo. A device for colorectal PDT treatment is also provided, comprising laser radiation source operating at about 400 and 800 nm; excitation laser radiation source operating at about 650 nm for fluorescence measurements; multichannel dosimetry device; long pass filter; waveguides and measurement probes.

Claims

1. A photosensitizer composition comprising;

a) tetrapyrrole and its derivatives, selected from the group consisting of porphyrins, chlorins, pheophorbides and bacteriopheophorbides; and

b) appropriate excipients and carriers.

2. The photosensitizer composition according to claim 1, wherein said excipients and carriers are selected in relation to the pharmaceutical dosage form adopted according to the route of administration selected.

3. The photosensitizer composition according to claim 1, wherein said photosensitizer is Temoporfin (m-THPC).

4. An applicator for colorectal PDT treatment comprising;

a) a hollow-shaped element with at least one center conduit;

b) at least two conduits placed opposite each other at the surface of said hollow-shaped element parallel to said center conduit; and

c) at least two conduits with a slope.

5. The applicator of claim 4, wherein adjustable spacers may be placed in the conduits to prevent damage to the anal mucosa by inserting measurement probes.

6. The applicator of claim 4, wherein said conduit'"'"'s slope is about 35 degrees.

7. The applicator of claim 4, further comprising a material which is used to monitor the fluence rate at the same time as doing optical spectroscopy.

8. The applicator of claim 4, wherein said material is a polymeric material which has a Raman peak from a C-H stretch/an amide group.

9. A measurement probe device comprising,

a) a hollow element of medical-grade metal;

b) at least two waveguides, placed at a determined core-to-core distance of said hollow element of medical-grade metal; and

c) a fluorescence differential path length spectroscopy control unit.

10. The measurement probe device according to claim 9, wherein said waveguides have a slope at distal tips.

11. The measurement probe device according to claim 10, wherein said slope at the tip is about 35 degrees.

12. The measurement probe device according to claim 9, wherein at least one of said waveguides is a radiation delivery and radiation collector optical fiber.

13. The measurement probe device according to claim 9, wherein said hollow element of medical-grade metal is a stainless steel needle.

14. The measurement probe device according to claim 9, wherein at least one of said waveguide is a radiation collector optical fiber.

15. A device for colorectal PDT treatment comprising;

a) at least one radiation source;

b) a multichannel dosimetry device;

c) a long pass filter;

d) at least one waveguide; and

e) at least one measurement probe.

16. The device for colorectal PDT treatments according to claim 15, wherein said radiation source is a coherent or incoherent radiation source selected from the group consisting of lasers, white light sources, light emitting diodes, lamps, and a combination of these whose output can be regulated within a preselected spectral window.

17. The device for colorectal PDT treatments according to claim 15, wherein said at least one waveguide is an optical fiber selected from the group consisting of radial optical fibers, linear diffusers, balloon optical fibers, bifurcated optical fibers and combination of these.

18. The device for colorectal PDT treatments according to claim 15, wherein said radiation source is a laser radiation source operating at about 400 to about 800 nm.

19. The device for colorectal PDT treatments according to claim 15, wherein said radiation source is an excitation laser radiation source operating at about 650 nm for fluorescence measurements.

20. The device for colorectal PDT treatments according to claim 19, wherein said excitation laser radiation source is used with one or more laser beam splitters.

21. The device for colorectal PDT treatments according to claim 19, wherein means for shutter is placed in laser radiation path to control the excitation laser radiation for each measurement probe.

22. The device for colorectal PDT treatments according to claim 21, wherein said measurement probe is a measurement probe device whose outputs are processed with the aid of a fluorescence differential path length spectroscopy control unit.

23. The device for colorectal PDT treatments according to claim 15, wherein a data processing unit is used to manage fluorescence spectroscopy data, fluorescence differential path-length spectroscopy data, and signals measured with measurement probes.

24. A dynamic colorectal PDT method comprising the steps of

a) administering an effective dose of a photosensitizer composition;

b) placing at least one measurement probe and at least one treatment waveguide at a treatment site;

c) irradiating said treatment site; and

d) monitoring treatment parameters before, during and/or after irradiation.

25. The dynamic colorectal PDT method according to claim 24, wherein said method is to treat abnormal cell growth in anal tissue selected form the group consisting of perianal intraepithelial neoplasia grade III and intra-anal intraepithelial neoplasia grade 3.

26. The dynamic colorectal PDT method according to claim 24, wherein said photosensitizer composition is administrated topically, intravenously, orally or a combination of these.

27. The dynamic colorectal PDT method according to claim 24, wherein said at least one measurement probe is selected from the group consisting of passive probes, active probes and a combination of these.

28. The dynamic colorectal PDT method according to claim 24, wherein said at least one treatment waveguide is an optical fiber selected from the group consisting of radial optical fibers, linear diffusers, balloon optical fibers and combination of these.

29. The dynamic colorectal PDT method according to claim 24, wherein said treatment parameters monitored include explicit and implicit parameters and are selected from the group consisting of fluence, fluence rate, fluorescence, photosensitizer concentration, tissue oxygenation, saturation, blood volume and combinations of these.