BIOLOGICALLY ACTIVE ADDITIVE BASED ON MESOPOROUS SILICON DIOXIDE AND ON MICELLAR SOLUTIONS OF ACTIVE SUBSTRATES AND METHOD FOR PREPARING SAME

Abstract

The group of inventions provides a biologically active additive and a method for preparing same. The biologically active additive is a micellar solution of an active substance in at least one emulsifier selected from the group comprising: polysorbate 20, polysorbate 80, polysorbate 20 and polysorbate 80, the emulsifier being adsorbed on amorphous mesoporous silicon dioxide nanoparticles having mesopore size from 0.2 to 1.8 nm by way of stirring in a disperser. The active substance may be selected from the group comprising: curcumin extract and rutin extract, dihydroquercetin extract, dihydroquercetin extract with quercetin extract, mixed tocopherol concentrate, cannabis oil with cannabidiol level up to 85%, cannabidiol isolate, cannabidiol isolate with mixed tocopherol concentrate, ADEK vitamin mixture concentrate, Sophora japonica extract, rosemary extract, cholecalciferol, thioctic acid, ferulic acid, resveratrol, resveratrol with ferulic acid, boswellia extract, betulin extract, icariin extract, chlorophyll extract, cannabidiol isolate with melatonin, cannabis oil having cannabidiol level up to 85% with passionflower extract, vardenafil, tadalafil, curcumin extract with soy lecithin, paclitaxel extract, collagen extract with soy lecithin. A method for preparing a biologically active additive comprises loading, into the disperser, an active substance in at least one emulsifier selected from the group comprising: polysorbate 20, polysorbate 80, polysorbate 20 and polysorbate 80, heating to a temperature of 80-90° C. while stirring continuously at from about 1000 rpm to about 2000 rpm, cooling to a temperature from below 60° C. to below 45° C., adding amorphous mesoporous silicon dioxide having a mesopore size from 0.2 to 1.8 nm, stirring at from about 1000 rpm to about 2000 rpm for about 0.5 h, followed by an increase in the stirring speed to 7000-9000 rpm until producing a homogeneous product in the form of a loose powder. The group of inventions provides improved bioavailability of the active substance.

Claims

1. A biologically active additive being a micellar solution of an active substance in at least one emulsifier selected from the group comprising: polysorbate 20, polysorbate 80, polysorbate 20 and polysorbate 80, the emulsifier being adsorbed on amorphous mesoporous silicon dioxide nanoparticles having mesopore size from 0.2 to 1.8 nm by way of stirring in a disperser.

2. The biologically active additive of claim 1, wherein the active substance is selected from the group comprising: curcumin extract and rutin extract, dihydroquercetin extract, dihydroquercetin extract with quercetin extract, mixed tocopherol concentrate, cannabis oil with cannabidiol level up to 85%, cannabidiol isolate, cannabidiol isolate with mixed tocopherol concentrate, ADEK vitamin mixture concentrate, Sophora japonica extract, rosemary extract, cholecalciferol, thioctic acid, ferulic acid, resveratrol, resveratrol with ferulic acid, boswellia extract, betulin extract, icariin extract, chlorophyll extract, cannabidiol isolate with melatonin, cannabis oil having cannabidiol level up to 85% with passionflower extract, vardenafil, tadalafil, curcumin extract with soy lecithin, paclitaxel extract, collagen extract with soy lecithin.

3. A method for producing a biologically active additive of claim 1, the method comprising loading, into the disperser, an active substance in at least one emulsifier selected from the group comprising: polysorbate 20, polysorbate 80, polysorbate 20 and polysorbate 80, heating to a temperature of 80-90° C. while stirring continuously at from about 1,000 rpm to about 2,000 rpm, cooling to a temperature from below 60° C. to below 45° C., adding amorphous mesoporous silicon dioxide having a mesopore size from 0.2 to 1.8 nm, stirring at from about 1,000 rpm to about 2,000 rpm for about 0.5 h, followed by increasing the stirring speed to 7,000-9,000 rpm until a homogeneous product in loose powder form is produced.

4. A method for preparing the biologically active additive of claim 3, wherein the active substance is selected from the group comprising: curcumin extract and rutin extract, dihydroquercetin extract, dihydroquercetin extract with quercetin extract, mixed tocopherol concentrate, cannabis oil with cannabidiol level up to 85%, cannabidiol isolate, cannabidiol isolate with mixed tocopherol concentrate, ADEK vitamin mixture concentrate, Sophora japonica extract, rosemary extract, cholecalciferol, thioctic acid, ferulic acid, resveratrol, resveratrol with ferulic acid, boswellia extract, betulin extract, icariin extract, chlorophyll extract, cannabidiol isolate with melatonin, cannabis oil having cannabidiol level up to 85% with passionflower extract, vardenafil, tadalafil, curcumin extract with soy lecithin, paclitaxel extract, collagen extract with soy lecithin.

Description

EXPERIMENTAL

[0020] 1. A weighed portion of curcumin extract in the amount of 1.1 g (11%) and rutin extract in the amount was 0.3 g (3%) was dissolved while continuously stirring and heating in polysorbate 80 at 1,000 rpm to a temperature of 80° C. The resulting dark solution (10 g) was cooled to a temperature below 60° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 1,000 rpm. The speed was then increased to 8,000 rpm for increased uniformity of substances distribution. At 10 g (40%):15 g (60%) ratio, a yellow loose product was produced.

[0021] 2. A weighed portion of dihydroquercetin extract in the amount of 1 g (10%) was dissolved while continuously stirring and heating in polysorbate 20 at 2,000 rpm to a temperature of 90° C. The resulting dark solution (10 g) was cooled to a temperature below 45° C. and added to 20 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 2,000 rpm. The speed was then increased to 8,000 rpm for increased dispersibility and uniformity of loose powder distribution.

[0022] 3. A weighed portion of dihydroquercetin extract in the amount of 0.5 g (5%) and quercetin extract (0.5 g (5%) was dissolved while continuously stirring at 1,500 rpm and heating to 85° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting solution (10 g} was cooled and added to 15 g of mesoporous silicon dioxide while continuously stirring in the IKA T 50 digital disperser at 1,500 rpm for 0.5 h. The stirring speed was then increased to 8,000 rpm; at 10 g (40%):15 g (60%) ratio, a yellow loose powder was produced.

[0023] 4. A weighed portion of mixed tocopherol concentrate in the amount of 1.5 g (15%) was dissolved while continuously stirring and heating to 90° C. in a mixture of polysorbates 80 and 20, at 1,500 rpm. The resulting solution (10 g) was cooled to a temperature below 50° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 2,000 rpm. The speed was then increased to 8,000 rpm for improved dispersibility of reactants. At 10 g (40%):15 g (60%) ratio, a yellow loose powder was produced.

[0024] 5. A weighed portion of cannabis oil having cannabidiol level up to 85% in the amount of 2 g (20%) was dissolved in polysorbate 80 while continuously stirring at 1,000 rpm and heating to 80° C. The resulting solution in the amount of 10 g was cooled to a temperature below 55° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 1,500 rpm. The speed was then increased to 8,000 rpm for increased uniformity of reactant distribution. At 10 g (40%):15 g (60%) ratio, a dark-yellow loose powder was produced.

[0025] 6. A weighed portion of cannabidiol isolate in the amount of 2 g (20%) was dissolved in polysorbate 20 while continuously stirring and heating. The resulting slightly colored solution (10 g) was cooled to a temperature below 45° C. and added to 15 g of mesoporous silicon dioxide while stirring for 0.5 h in the IKA T 50 digital disperser. The speed was then increased to 8,000 rpm for increased dispersibility of substances. At 10 g (40%):15 g (60%) ratio, a light loose powder was produced.

[0026] 7. A weighed portion of cannabidiol isolate in the amount of 1.8 g (18%) and 0.2 g (2%) of mixed tocopherol concentrate was dissolved in a mixture of polysorbates 80 and 20 while stirring at 2,000 rpm and heating to 80° C. The resulting dark solution in the amount of 10 g was cooled to a temperature below 60° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring at 2,000 rpm for 0.5 h in the IKA T 50 digital disperser. The stirring speed was then increased to 9,000 rpm to reduce clustering. At 10 g (40%):15 g (60%) ratio, a yellow loose powder was produced.

[0027] 8. A weighed portion of ADEK vitamin mix concentrate in the amount of 2 g (20%) was dissolved in polysorbate 80 while continuously stirring at 1,500 rpm and heating to 85° C. The resulting solution (10 g) was cooled to a temperature below 45° C. and added to 15 g of mesoporous silicon dioxide while stirring in the IKA T 50 digital disperser for 0.5 h at 1,000 rpm. The speed was then increased to 9,000 rpm for improved dispersibility of the substances. At 10 g (40%):15 g (60%) ratio, a yellow loose powder was produced.

[0028] 9. A weighed portion of Sophora japonica extract in the amount of 1 g (10%) was dissolved while continuously stirring at 2,000 rpm and heating to 90° C. in polysorbate 20. The resulting dark solution (10 g) was cooled to a temperature below 60° C. and added to 20 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 1,000 rpm. The speed was then increased to 8,000 rpm for increased dispersibility and uniformity of distribution of substances. At 10 g (33.3%):20 g (66.6%) ratio, a light yellow loose powder was produced.

[0029] 10. A weighed portion of rosemary extract in the amount of 1 g (10%) was dissolved while continuously stirring at 1,500 rpm and heating to 80° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting solution (10 g) was cooled to a temperature below 55° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 1,000 rpm. The speed was then increased to 8,000 rpm for improved dispersibility of reactants. At 10 g (40%):15 g (60%) ratio, a yellow loose powder was produced.

[0030] 11. A weighed portion of cholecalciferol (vitamin D3) in the amount of 1.5 g (15%) was dissolved while stirring at 2,000 rpm and heating to 90° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting solution (10 g) was cooled to a temperature below 50° C. and added to 20 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring vigorously in the IKA T 50 digital disperser for 0.5 h at 1,500 rpm. The speed was then increased to 9,000 rpm to improve dispersibility of reactants. At 10 g (33.3%):20 g (66.6%) ratio, a white loose powder was produced.

[0031] 12. A weighed portion of thioctic acid in the amount of 1.5 g (15%) was dissolved while continuously stirring at 1,000 rpm and heating to 80° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting solution (10 g) was cooled to a temperature below 50° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 1,500 rpm. The speed was then increased to 8,000 rpm to improve dispersibility of reactants. At 10 g (40%):15 g (60%) ratio, a while loose powder was produced.

[0032] 13. A weighed portion of ferulic acid in the amount of 1.5 g (15%) was dissolved while continuously stirring at 1,000 rpm and heating to 85° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting solution (10 g) was cooled to a temperature below 45° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 1,500 rpm. The speed was then increased to 8,000 rpm for improved dispersibility of reactants. At 10 g (40%):15 g (60%) ratio, a while loose powder was produced.

[0033] 14. A weighed portion of resveratrol in the amount of 1.5 g (15%) was dissolved while continuously stirring at 1,000 rpm and heating to 85° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting solution (10 g) was cooled to a temperature below 45° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 1,000 rpm. The speed was then increased to 8,000 rpm for improved dispersibility of reactants. At 10 g (40%):15 g (60%) ratio, a while loose powder was produced.

[0034] 15. A weighed portion of resveratrol in the amount of 0.5 g (5%) and ferulic acid in the amount of 0.5 g (5%) was dissolved while stirring at 1,500 rpm and heating to 90° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting solution (10 g) was cooled to a temperature below 50° C. and added to 20 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring vigorously in the IKA T 50 digital disperser for 0.5 h at 2,000 rpm. The speed was then increased to 9,000 rpm to improve dispersibility of reactants. At 10 g (33.3%):20 g (66.6%) ratio, a white loose powder was produced.

[0035] 16. A weighed portion of boswellia extract in the amount of 1.2 g (12%) was dissolved while continuously stirring at 1,000 rpm and heating to 90° C. in polysorbate 80. The resulting solution (10 g) was cooled to a temperature below 50° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 1,000 rpm. The speed was then increased to 8,000 rpm for increased uniformity of substance distribution. At 10 g (40%):15 g (60%) ratio, a yellow loose product was produced.

[0036] 17. A weighed portion of betulin extract in the amount of 1.5 g (15%) was dissolved while continuously stirring at 1,500 rpm and heating to 85° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting solution (10 g) was cooled to a temperature below 45° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h at 1,500 rpm. The speed was then increased to 8,000 rpm for improved dispersibility of reactants. At 10 g (40%):15 g (60%) ratio, a while loose powder was produced.

[0037] 18. A weighed portion of icariin extract in the amount of 1.5 g (15%) was dissolved while continuously stirring at 1,000 rpm and heating to 85° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting solution (10 g) was cooled to a temperature below 45° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring in the IKA T 50 digital disperser for 0.5 h (at 1,000 rpm). The speed was then increased to 8,000 rpm for improved dispersibility of reactants. At 10 g (40%):15 g (60%) ratio, a yellow loose powder was produced.

[0038] 19. A weighed portion of chlorophyll extract in the amount of 0.5 g (5%) was dissolved while continuously stirring at 2,000 rpm and heating to 90° C. in a mixture of polysorbate 80 and polysorbate 20. The resulting dark solution (10 g) was cooled to a temperature below 50° C. and added to 15 g of amorphous silicon dioxide while continuously stirring at 2,000 rpm in the IKA T 50 digital disperser for 0.5 h. The stirring speed was then increased to 8,000 rpm. At 10 g (40%):15 g (60%) ratio, a green loose powder was produced.

[0039] 20. A weighed portion of cannabidiol isolate in the amount of 1.5 g (15%) and 0.5 g (5%) of melatonin was dissolved in a mixture of polysorbate 80 and polysorbate 20 while stirring at 1,000 rpm and heating to 90° C. The resulting dark solution in the amount of 10 g was cooled to a temperature below 50° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring at 1,000 rpm for 0.5 h in the IKA T 50 digital disperser. The stirring speed was then increased to 9,000 rpm to reduce clustering. At 10 g (40%):15 g (60%) ratio, a while loose powder was produced.

[0040] 21. A weighed portion of cannabis oil having cannabidiol level up to 85% in the amount of 1.5 g (15%) and passionflower extract in the amount of 0.5 g (5%) was dissolved in polysorbate 80 while continuously stirring at 1,000 rpm and heating to 90° C. The resulting solution (10 g) was cooled to a temperature below 60° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.2 to 1.8 nm while stirring at 1,000 rpm in the IKA T 50 digital disperser for 0.5 h. The speed was then increased to 8,000 rpm for increased uniformity of reactant distribution. At 10 g (40%):15 g (60%) ratio, a dark-yellow loose powder was produced.

[0041] 22. A weighed portion of vardenafil in the amount of 0.5 g (5%) was dissolved in polysorbate 20 while continuously stirring at 2,000 rpm and heating to 90° C. The resulting solution (10 g) was cooled to a temperature below 60° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.8 to 1.2 nm while continuously stirring at 1,000 rpm in the IKA T 50 digital disperser for 0.5 h. The stirring speed was increased to 7,000 rpm for complete homogenization of reaction mass. At 10 g (40%):15 g (60%) ratio, a loose powder was produced.

[0042] 23. A weighed portion of tadalafil in the amount of 0.5 g (5%) was dissolved in polysorbate 20 while continuously stirring at 1,500 rpm and heating to 90° C. The resulting solution (10 g) was cooled to a temperature below 60° C. and added to 15 g of amorphous silicon dioxide having mesopore size from 0.8 to 1.2 nm while continuously stirring at 1,500 rpm in the IKA T 50 digital disperser for 0.5 h. The stirring speed was increased to 7,000 rpm for complete homogenization of reaction mass. At 10 g (40%):15 g (60%) ratio, a loose powder was produced.

[0043] 24. A weighed portion of curcumin extract (1 g (10%)) and soy lecithin (0.5 g (5%)) was dissolved while heating to 80° C. and continuously stirring at 1,500 rpm in polyethylene glycol. The resulting dark solution in the amount of 10 g was cooled to a temperature below 50° C. and added to 20 g of amorphous silicon dioxide having mesopore size from 0.8 to 1.2 nm while stirring in the IKA T 50 digital disperser at 1,500 rpm for 0.5 h. The speed was then increased to 9,000 rpm to reduce clustering. At the given ratio of 10 g (33.3%) to 20 g (66.6%), a yellow loose powder was produced.

[0044] 25. A weighed portion of paclitaxel extract (1 g (10%)) and soy lecithin (0.5 g (5%)) was dissolved while heating to 85° C. and continuously stirring at 1,000 rpm in polyethylene glycol. The resulting yellow solution in the amount of 10 g was cooled to a temperature below 50° C. and added to 20 g of amorphous silicon dioxide having mesopore size from 0.8 to 1.2 nm while stirring at 2,000 rpm in the IKA T 50 digital disperser for 0.5 h. The speed was then increased to 9,000 rpm to reduce clustering. At the given ratio of 10 g (33.3%) to 20 g (66.6%), a loose powder was produced.

[0045] 26. A weighed portion of collagen extract (1 g (10%)) and soy lecithin (0.5 g (5%)) was dissolved while heating to 90° C. and continuously stirring at 1,000 rpm in polyethylene glycol. The resulting yellow solution in the amount of 10 g was cooled to a temperature below 45° C. and added to 20 g of amorphous silicon dioxide having mesopore size from 0.8 to 1.2 nm while stirring at 1,000 rpm in the IKA T 50 digital disperser for 0.5 h. The speed was then increased to 9,000 rpm to reduce clustering. At the given ratio of 10 g (33.3%) to 20 g (66.6%), a loose powder was produced.

CONCLUSIONS

[0046] 1. It has been experimentally shown that mechanochemical activation on a high-intensity disperser was of a general nature for a wide range of organic natural and synthetic compounds.

[0047] 2. The subject technology is advantageous over known methods in that it provides: complete exclusion of organic solvents from the process, two-stageness, environmental safety, scalability, flexibility of technology.

[0048] 3. The subject technology eliminates: undesirable properties of a pharmaceutical substance, undesirable side effects, unpleasant organoleptic properties.

[0049] 4. Provided are increased stability under storing the active substrate and increased resistance to environmental factors (oxidative degradation).

[0050] 5. The resulting powders acquire the optimal flowability required for modern high-speed tablet presses, as well as for use in hard gelatin capsules or in powders.

[0051] 6. The organic phase of synthesized powders is completely soluble in water to form stable micellar solutions, the bioavailability of which correlates with the stock solutions of active substances in surfactants.