Emulsioin suitable for administering a poorly water-soluble photosensitizing compound and use thereof

• US 5,616,342 A
• Filed: 04/11/1995
• Issued: 04/01/1997
• Est. Priority Date: 04/11/1995
• Status: Expired due to Term

• Current Assignee: Adgero Biopharmaceuticals, Inc. (Kintara Therapeutics, Inc.), PDT Inc.
• Original Assignee: PDT Inc., Pharmacia & Upjohn AB (Pharmacia Corp.)
• Inventors: Lyons, Robert T.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/419,911
• Time in Patent Office: 721 Days
• Field of Search: 424/450, 514/410
• US Class Current: 424/450
• CPC Class Codes: A61K 31/409 having four such rings, e.g. porphine derivatives, bilirubin, biliverdine hemin, hematin A61K31/555
• 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: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence

Abstract

Emulsion comprising a lipoid as a hydrophobic phase dispersed in a hydrophilic phase, a poorly water-soluble photosensitizing compound, surfactant, and as a cosurfactant a salt of a bile acid is provided that is suitable for administering to a patient.

Claims

1. An emulsion for administering a poorly water-soluble, pharmacologically active, photosensitizing pyrrole-based macrocyclic compound to a patient comprising a pharmacologically acceptable lipid as a hydrophobic phase dispersed in a hydrophilic phase, an effective amount of said photosensitizing pyrrole-based macrocyclic compound, a phospholipids stabilizer, and as a costabilizer, a pharmaceutically acceptable salt of a bile acid selected from the group consisting of cholic acid, deoxycholic acid, glycocholic acid;

and mixtures thereof, and wherein the concentration of said pharmaceutically acceptable salt is about 0.01 to about 1.0 g/100 ml of the emulsion.

2. The emulsion of claim 1 wherein said lipoid is selected from the group consisting of soybean oil, safflower oil, marine oil, black currant seed oil, borage oil, palm kernel oil, sunflower oil, cotton seed oil, olive oil, coconut oil and physical or interesterified mixtures thereof.

3. The emulsion of claim 1 wherein said lipoid is a triglyceride having a fatty acid chain length of 8 to 10 carbons.

4. The emulsion of claim 1 wherein said lipoid is the triglycerides distilled from coconut oil.

5. The emulsion of claim 1 wherein said stabilizer is egg yolk phospholipids.

6. The emulsion of claim 1 wherein the particles have a mean diameter of less than 5 mlcrons.

7. The emulsion of claim 1 wherein said diameter is 0.5 mlcrons or less.

8. The emulsion of claim 1 wherein the amount of said photosensitizing compound is about 0.01 to about 1 g/100 ml, the amount of said lipoid is about 5 to about 40 g/100 ml, and the amount of said salt of a bile acid is about 0.05 to about 0.4 g/100 ml.

9. The emulsion of claim 1 wherein the amount of said stabilizer is about 0.3 to about 3 g/100 ml.

10. The emulsion of claim 1 which further includes an isotonic agent.

11. The emulsion of claim 10 wherein said isotonic agent is present in an amount of about 0.4 to about 4 g/100 ml.

12. The emulsion of claim 10 wherein said isotonic agent is glycerin.

13. The emulsion of claim 1 which further includes an antioxidant.

14. The emulsion of claim 13 wherein the antioxidant is present in an amount of about 0.02 to about 0.2 g/100 ml.

15. The emulsion of claim 14 wherein said antioxidant is α

-tocopherol.

16. The emulsion of claim 1 wherein said salt of a bile acid is a salt of cholic acid.

17. The emulsion of claim 16 wherein said salt is sodium cholate.

18. The emulsion of claim 1 which further includes ethyl alcohol.

19. The emulsion of claim 18 wherein the amount of said ethyl alcohol is about 0.2 to about 2 grams/100 ml.

20. The emulsion of claim 1 wherein said pyrrolic macrocyclic compound is selected from the group consisting of at least one of naturally occurring or synthetic porphyrins, naturally occurring or synthetic chlorins, naturally occurring or synthetic bacteriochlorins, synthetic isobacteriochlorins, phthalocyanines, naphthalocyanines, and expanded pyrrole-based macrocyclic systems.

21. The emulsion of claim 20 wherein said pyrrolic macrocyclic compound is tin ethyl etiopurpurin.

22. The emulsion of claim 20 wherein said pyrrolic macrocyclic compound is zinc phthalocyanine.

23. The emulsion of claim 20 wherein said pyrrolic macrocyclic compound is benzoporphyrin derivative.

24. The emulsion of claim 20 wherein said pyrrolic macrocyclic compound is meso-tetra (hydroxyphenyl) chlorin.

25. A method for treating a patient with a photosensitizing compound which comprises administering to said patient the emulsion of claim 1.

26. The method of claim 25 wherein said administering is intravenously.

27. The method of claim 25 which further comprises exposing said pyrrolic macrocyclic compound to light after administering in order to activate said compound.

28. A method for diagnosing a patient for tumors which comprises administering to said patient the emulsion of claim 1 and then exposing said patient to light of a suitable wavelength that would induce fluorescence of any photosensitizing compound preferentially maintained by hyperproliferating or abnormal cells in said patient.

29. The emulsion of claim 1 having a pH of about 7.5 to about 9.5.

30. The emulsion of claim 20 wherein said expanded pyrrole-base macrocyclic systems is selected from the group consisting of porphycenes, sapphyrins and texaphyrins.

31. The emulsion of claim 1 wherein said stabilizer consists of phospholipids in an amount of about 0.3 to about 3 g/100 ml of said emulsion and said costabilizer consists of said salt of a bile acid in an amount of about 0.05 to about 0.4 g/100 ml.