Formulation for I.V. administration of the boron delivery drug, boronophenylalanine (BPA)

• US 5,935,944 A
• Filed: 02/20/1996
• Issued: 08/10/1999
• Est. Priority Date: 09/10/1993
• Status: Expired due to Fees

• Current Assignee: Neuton Technologies Inc.
• Original Assignee: Neuton Technologies Inc.
• Inventors: LaHann, Thomas R.
• Primary Examiner(s): FONDA, KATHLEEN KAHLER
• Application Number:
  US08/603,332
• Time in Patent Office: 1,267 Days
• Field of Search: 568/6, 514/23, 514/64, 536/124
• US Class Current: 514/64
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations

Abstract

A process and product formulated by complexing boronophenylalanine (BPA) and related compounds with a saccharide in an aqueous solution are disclosed. Formation of the complex is facilitated by raising the pH of the solution to a higher pH of about 10 or by lowering the pH of the solution to a lower pH of about 2 and then readjusting the pH to a body physiological pH of about 7.4. This BPA saccharide complex can then be delivered by i.v. or other injection or administered orally as a key component of the BNCT cancer treatment process The pH manipulation causes a much higher solubility of BPA or related compounds and thus a higher boron concentration in the tumor, thereby improving the therapy.

Claims

1. A process for formulating a boronophenylalanine solution for use in a boron neutron capture therapy cancer treatment, the process comprising:

a. mixing boronophenylalanine (BPA) with a saccharide in water, thereby forming a mixed solution;

b. increasing the pH of the mixed solution to a pH of about 10; and

then,

c. readjusting the pH of the solution to about 7.4, thereby forming a high concentration BPA solution at a physiologically relevant pH.

2. A process as recited in claim 1 wherein the molar ratio of BPA to the saccharide is between about 10:

1 to 1;

10.

3. A process as recited in claim 1 wherein the saccharide is fructose.

4. A process for formulating a boronophenylalanine solution for use in a boron neutron capture therapy cancer treatment, the process comprising:

a. mixing boronophenylalanine (BPA) with a saccharide in water, thereby forming a mixed solution;

b. decreasing the pH of the mixed solution to a pH of about 2; and

then,

c. readjusting the pH of the solution to about 7.4, thereby forming a high concentration BPA solution at a physiologically relevant pH.

5. A process as recited in claim 4 wherein the molar ratio of BPA to the saccharide is between about 10:

1 to 1;

10.

6. A process as recited in claim 4 wherein the saccharide is fructose.

7. A product for use in boron neutron capture therapy cancer treatment made by the method comprising:

a. mixing boronophenylalanine (BPA) with a saccharide in water, thereby forming a mixed solution;

b. increasing the pH of the mixed solution to a pH of about 10; and

then,

c. readjusting the pH of the solution to about 7.4, thereby forming a high concentration BPA solution of greater than 50 mg/ml at a physiologically relevant pH.

8. A product as recited in claim 7, wherein the molar ratio of BPA to the saccharide is between about 10:

1 to 1;

10.

9. A product as recited in claim 7, wherein the saccharide is fructose.

10. A product as recited in claim 7, wherein the BPA concentration is greater than 75 mg/ml.

11. A product as recited in claim 7, wherein the BPA concentration is greater than 100 mg/ml.

12. A product for use in boron neutron capture therapy cancer treatment made by the method comprising:

a. mixing boronophenylalanine (BPA) with a saccharide in water, thereby forming a mixed solution;

b. decreasing the pH of the mixed solution to a pH of about 2; and

then,

c. readjusting the pH of the solution to about 7.4, thereby forming a high concentration BPA solution of greater than 50 mg/ml at a physiologically relevant pH.

13. A product as recited in claim 12, wherein the molar ratio of BPA to the saccharide is between about 10:

1 to 1;

10.

14. A product as recited in claim 12, wherein the saccharide is fructose.

15. A product as recited in claim 12, wherein the BPA concentration is greater than 75 mg/ml.

16. A product as recited in claim 12, wherein the BPA concentration is greater than 100 mg/ml.

17. An aqueous solution for use in a boron neutron capture therapy cancer treatment comprising, in a concentration of greater than 50 mg/ml, a compound selected from the group consisting of boronphenylalanine (BPA), a structural modification of BPA, or an amino acid analog of BPA.

18. A solution as recited in claim 17, wherein the BPA concentration is greater than 75 mg/ml.

19. A solution as recited in claim 17, wherein the BPA concentration is greater than 100 mg/ml.