Method for enhancing the solubility of the boron delivery drug, boronophenylalanine (BPA)

• US 5,492,900 A
• Filed: 09/10/1993
• Issued: 02/20/1996
• 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): Robinson, Douglas W.
• Assistant Examiner(s): Fonda, Kathleen Kahler
• Application Number:
  US08/119,982
• Time in Patent Office: 893 Days
• Field of Search: 514/23, 514/64
• 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 d,1- or 1-p-boronophenylalanine (BPA) with a saccharide in an aqueous solution formation of the complex being facilitated by raising the pH of this solution to a higher pH of about 10 or 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 and thus a higher boron concentration in the tumor, thereby improving the therapy.

Claims

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

a. mixing a molar ratio of between 1.0;

0.5 and 1.0;

2.0 of p-boronophenylalanine with a monosaccharide in about pH 7.4 distilled water, thereby forming a mixed solution;

b. increasing the pH of the mixed solution to a pH of about 10 for a period of 5 to 10 minutes; and

then

c. readjusting the pH of the solution to about 7.4, thereby forming a concentration of boronophenylalanine solution of greater than about 150 mg/ml at a physiologically relevant pH, said concentration delivering more than 20 ppm boron to tumor tissue when the solution is used as an intravenous infusion into an animal.

2. A process as recited in claim 1 wherein the ratio of boronophenylalanine to the monosaccharide is about 1:

1.

3. A process as recited in claim 2 wherein the monosaccharide is fructose.

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

a. mixing a molar ratio of between 1.0;

0.5 and 1.0;

2.0 of p-boronophenylalanine with fructose in about 7.4 pH distilled water, thereby forming a mixed solution;

b. increasing the pH of the mixed solution to a pH of about 10 for a period of 5 to 10 minutes; and

then

c. readjusting the pH of the solution to about 7.4 thereby forming a concentration of boron and boronophenylalanine solution of greater than about 150 mg/ml at a physiologically relevant pH, said concentration delivering more than 20 ppm boron to tumor tissue when the solution is used as an intravenous infusion into an animal.

5. The process as recited in claim 4 wherein the ratio of boronophenylalanine to fructose is about 1:

1.

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

a. mixing a molar ratio of between 1.0;

0.5 and 1.0;

2.0 of p-boronophenylalanine with a monosaccharide in about pH 7.4 distilled water, thereby forming a mixed solution;

b. decreasing the pH of the mixed solution to a pH of about 2 for a period of 5 to 10 minutes; and

then

c. readjusting the pH of the solution to about 7.4, thereby forming a concentration of boronophenylalanine solution of greater than about 150 mg/ml at a physiologically relevant pH, said concentration delivering more than 20 ppm boron to tumor tissue when the solution is used as an intravenous infusion into an animal.

7. A process as recited in claim 6 wherein the ratio of boronophenylalanine to the monosaccharide is about 1:

1.

8. A process as recited in claim 7 wherein the monosaccharide is fructose.