Significance of dosimetry in photodynamic therapy of injured arteries

• US 6,520,981 B1
• Filed: 10/02/2000
• Issued: 02/18/2003
• Est. Priority Date: 10/01/1999
• Status: Expired due to Fees

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: LaMuraglia, Glenn Michael
• Primary Examiner(s): Walberg, Teresa
• Assistant Examiner(s): DAHBOUR, HENRY
• Application Number:
  US09/678,174
• Time in Patent Office: 869 Days
• Field of Search: 607/89, 607/88, 607/92, 607/94, 606/15, 606/194, 606/28, 606/7, 606/14, 606/3, 606/16, 604/913, 604/20
• US Class Current: 607/89
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• CPC Class Codes: A61N 5/0601 Apparatus for use inside the body
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent

Abstract

Photodynamic therapy (PDT), the light activation of methylene blue or benzoporphyrin derivatives to produce free-radicals, was shown in vivo to inhibit intimal hyperplasia (IH) and restenosis. The present invention provides an effective clinical approach for PDT treatment which modulates the vascular intervention injury healing response.

Claims

1. A method for modulating restenosis in a subject, comprising the steps of non-systemically administering a therapeutically effective amount of a benzoporphyrin derivative or methylene blue to an injury site in vivo and irradiating the injury site with sufficient light energy between about 300 and 900 nm, such that undesired cells at the injury site are destroyed and restenosis in the subject is modulated.

2. The method of claim 1, wherein the light energy is delivered by a high energy light source.

3. The method of claim 2, wherein the high energy light source is a laser.

4. The method of claim 1, wherein the therapeutically effective amount of the benzoporphyrin derivative is between about 0.5 μ

g/ml and about 25 μ

g/ml.

5. The method of claim 4, wherein the light energy is about 100 J/cm².

6. The method of claim 1, wherein the therapeutically effective amount of the methylene blue is between about 5 μ

g/ml and about 1000 μ

g/ml.

7. The method of claim 6, wherein the light energy is about 100 J/cm².

8. A method for modulating intimal hyperplasia in a subject, comprising the steps of non-systemically administering a therapeutically effective amount of a benzoporphyrin derivative or methylene blue to undesired cells of a target tissue site in vivo and irradiating the undesired cells of the target tissue treated injury site with a sufficient amount of light energy between about 300 and 900 nm, such that the undesired cells of the target tissue are eradicated.

9. The method of claim 8, wherein the light energy is delivered by a high energy light source.

10. The method of claim 9, wherein the high energy light source is a laser.

11. The method of claim 8, wherein the therapeutically effective amount of the benzoporphyrin derivative is between about 0.5 μ

g/ml and about 25 μ

g/ml.

12. The method of claim 11, wherein the light energy is about 100 J/cm².

13. The method of claim 8, wherein the therapeutically effective amount of the methylene blue is between about 5 μ

g/ml and about 1000 μ

g/ml.

14. The method of claim 13, wherein the light energy is about 100 J/cm².

15. The method of claim 8, wherein the target tissue site is the subluminal space of a blood vessel and the cells are selected from the group consisting of smooth muscle cells, fibroblasts, myoblasts, and combinations thereof.