Method of producing a composition for boron neutron capture therapy of malignant tumors (embodiments)
Medical technologies for the creation of target agents for boron-neutron capture therapy of oncological diseases. In a first method variant for preparing a composition for boron neutron capture therapy of malignant tumors containing boron nanoparticles less than 100 nm includes: elemental boron powder being placed in water and treated for 0.5 to 800 minutes with ultrasound with vibration intensity from 1, 0 to 1000.0 W/cm 3 and the output power greater than 100.0 W. In a second method variant, elemental boron powder is placed in water and treated for 30 to 300 minutes with ultrasound with a same vibration intensity and output power, then the upper part of the composition is taken in a volume less than 50.0 vol. % of total composition volume and treated with ultrasound with vibration intensity from 1.0 to 1000.0 W/cm 3 and output power greater than 100.0 W for 250-300 minutes.
1. A method of obtaining a composition for boron neutron capture therapy of malignant tumors comprising boron nanoparticles with particle size less than 100 nm, the method comprising:
i) placement of an elemental boron powder in water; and
ii) treatment of the elemental boron powder in water with ultrasound with a vibration intensity of between 1 W/cm 3 and 1000 W/cm 3 and an output power of more than 100 W, wherein the treatment with ultrasound is performed for a period of between 0.5 minutes and 800 minutes to obtain a composition for boron neutron capture therapy of malignant tumors.
2. The method of claim 1 , further comprising adding to the elemental boron powder in water a water-soluble inorganic metal salt with an oxidation state of +1 or a mixture thereof before step ii) or during step ii).
3. The method of claim 2 , wherein the weight ratio of the elemental boron powder to the salt or to the mixture of salts is between 1:0.01 and 1:30.
4. The method of claim 2 , wherein the water-soluble inorganic metal salt is selected from chloride, nitrate, sulfate, sulfite, and a mixture thereof.
5. The method of claim 4 , wherein the chloride is selected from sodium, potassium, lithium chloride, and a mixture thereof.
6. The method of claim 1 , further comprising adding one or more stabilizers to the composition.
7. The method of claim 6 , wherein the one or more stabilizers are selected from organic metal salts or their mixtures, inorganic metal salts with an oxidation state equal to or greater than +2, and compounds selected from blood plasma proteins, antibodies, hormones, E400-E499 additives, polysaccharides, fatty acids, proteins of vegetable origin, amino acid derivatives that are 1-amino-3-cyclobutane-1-carboxylic acid and 1-amino 3-cyclopentanecarboxylic acid, phenylalanine, linear and cyclic peptides, purines, pyrimidines, thymidines, nucleosides and nucleotides that are 3-carboranyl thymidine analogs, porphyrins, pluronics, polyhydric alcohols, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, and synthetic polyamino acids.
8. The method of claim 6 , wherein the one or more stabilizers are selected from citrates and acetates.
9. The method of claim 1 , wherein the elemental boron powder is selected from amorphous boron powder, coarse-crystalline boron powder, fine-crystalline boron powder, and mixtures thereof.
10. A method of obtaining a composition for boron neutron capture therapy of malignant tumors comprising boron nanoparticles with particle size less than 100 nm, the method comprising:
i) placement of an elemental boron powder in water;
ii) treatment of the elemental boron powder in water with ultrasound with a vibration intensity of between 1 W/cm 3 and 1000 W/cm 3 and an output power of more than 100 W, wherein the treatment with ultrasound is performed for a period of between 30 and 300 minutes to obtain an intermediate composition;
iii) taking an upper part of the intermediate composition in a volume of less than 50 vol. % of the total volume of the composition; and
iv) treating the composition of step iii) with ultrasound with a vibration intensity of between 1 W/cm 3 and 1000 W/cm 3 and an output power of more than 100 W, wherein the treating with ultrasound is performed for a period of between 250 and 300 minutes to obtain a composition for boron neutron capture therapy of malignant tumors.
11. The method of claim 10 , further comprising adding to the elemental boron powder in water a water-soluble inorganic metal salt with an oxidation state of +1 or a mixture thereof before or during step ii) or step iv).
12. The method of claim 11 , wherein the weight ratio of the elemental boron powder to the salt or to the mixture of salts is between 1:0.01 and 1:30.
13. The method of claim 11 , wherein the water-soluble inorganic metal salt is selected from chloride, nitrate, sulfate, sulfite, and a mixture thereof.
14. The method of claim 13 , wherein the chloride is selected from sodium, potassium, lithium chloride, and a mixture thereof.
15. The method of claim 10 , further comprising adding one or more stabilizers to the final composition.
16. The method of claim 15 , wherein the one or more stabilizers are selected from organic metal salts or their mixtures, inorganic metal salts with an oxidation state equal to or greater than +2, and compounds selected from blood plasma proteins, antibodies, hormones, E400-E499 additives, polysaccharides, fatty acids, proteins of vegetable origin, amino acid derivatives that are 1-amino-3-cyclobutane-1-carboxylic acid and 1-amino-3-cyclopentanecarboxylic acid, phenylalanine, linear and cyclic peptides, purines, pyrimidines, thymidines, nucleosides and nucleotides that are 3-carboranyl thymidine analogs, porphyrins, pluronics, polyhydric alcohols, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, and synthetic polyamino acids.
17. The method of claim 16 , wherein the one or more stabilizers are selected from citrates and acetates.
18. The method of claim 10 , wherein the elemental boron powder is selected from amorphous boron powder, coarse-crystalline boron powder, fine-crystalline boron powder, or mixtures thereof.