Soluble, stable, anti-inflammatory, proliferative, protective and mucoadhesive pharmaceutical compositions; use thereof for treating mucositis conditions and method for producing same; base pharmaceutical composition for preparing the pharmaceutical compositions and method for producing same

An anti-inflammatory, proliferative, protective and mucoadhesive, soluble and stable pharmaceutical composition comprising:

• i) a Curcuma Longa extract, a Bidens pilosa extract or a mixture of both as an active ingredient;
• ii) a solvent comprising distilled water, propylene glycol, polyethylene glycol 400 or a mixture of these;
• iii) a co-solvent comprising distilled water, propylene glycol or polyethylene glycol 400;
• iv) a surfactant comprising poly(oxyethylene), poly(oxypropylene), poloxamer 407, or poloxamer 188;
• v) a carrier comprising distilled water, propylene glycol or polyethylene glycol 400;
• and
• vi) an antioxidant comprising butylhydroxytoluene, a mixture of sodium bisulfite and sodium metabisulfite, or citric acid.

A process for obtaining an anti-inflammatory, proliferative, protective and mucoadhesive, soluble and stable liquid composition of curcuminoids and a glycerinated Bidens pilosa extract, comprising the following stages and steps:

• STAGE I
• (1) preparing a mixture of PEG 400 with propylene glycol and heating this mixture to 65° C.;
• (2) dividing a mass of poloxamer to be introduced into the formulation into two equal parts and dispersing each part in a portion of the propylene glycol and PEG 400 heated mixture;
• STAGE II
• (3) adding an extract of curcuminoids at a concentration of about 25 mg/mL into one portion of the heated mixture under mechanical agitation and maintaining it at a temperature of 65° C.;
• (4) adding the other part of the poloxamer mass to water to form an aqueous phase, at room temperature;
• and adding the curcuminoids mixture to the aqueous phase and mixing until the curcuminoids mixture is completely dispersed to form a first curcuminoids solution;
• STAGE III
• (5) pouring the first curcuminoids solution over the remaining STAGE I mixture containing propylene glycol and PEG 400 to obtain a final curcuminoids solution;
• (6) keeping the final curcuminoids solution under agitation until its temperature reaches 25° C., obtaining the total dissolution of the curcuminoids in the preparation;
• STAGE IV
• (7) preparing a composition of a Bidens pilosa extract to obtain a liquid formulation containing:
• 30% (v/v) propylene glycol;
• 30% (v/v) polyethylene glycol 400;
• and 40% (v/v) glycerinated extract of Bidens pilosa;
• and
• (8) mixing the final curcuminoids solution with the composition of Bidens pilosa, to obtain a liquid composition of curcuminoids and a glycerinated Bidens pilosa extract.

The process according to claim 44, wherein the curcuminoid extract is dissolved in an oily phase comprising:

• liquid vaseline (5% by weight of the oily phase);
• (stearic acid (3% by weight of the oily phase);
• cetyl alcohol (0.4% by weight of the oily phase);
• cetostearyl alcohol (0.35% of the oily phase);
• glyceryl monostearate (3% of the oily phase);
• isopropyl myristate (1% of the oily phase);
• Poloxamer (15% of the oily phase) and propylene glycol (6% of the oily phase);
• methylparaben (0.1 of the oily phase), propylparaben (0.05 of the oily phase) and butylhydroxytoluene (0.05% of the oily phase);
• wherein the curcuminoids are added to a melt of the oily phase maintained at 75 ° C. to a final concentration of 25 mg/mL and the mixture is agitated by mechanical agitation until the entire mass of curcuminoids is dissolved in the oily phase;
• the composition of the glycerinated extract of Bidens pilosa, at a concentration of 65% of the oily phase, is heated to a temperature of 75° C. and poured into the oily phase under constant mixing by mechanical agitation;
• and
• after the mixing is completed, cooling the mixture under agitation until the resulting product reaches a temperature of approximately 25° C.

A process for preparing a solid formulation containing an extract of curcuminoids and a glycerinated extract of Bidens pilosa comprising:

• (1) adding, for each solid pharmaceutical form, from 250 to 350 mg of mannitol, as diluent, to 25 to 200 mg of curcuminoids;
• (2) adding to the mixture (1) from 100 to 140 mg of poloxamer, as mucoadhesive agent;
• from 200 to 400 mg of microcrystalline cellulose;
• from 5 to 15 mg of sodium metabisulphite and from 20 to 40 mg of citric acid;
• (3) tamping all powders in a stainless steel tamper with 250 micrometer aperture mesh prior to performing a blending operation;
• (4) inserting the mixture of solid components into the processing chamber of a fluidized bed apparatus for mixing and granulation operations;
• (5) injecting heated air at 45-65° C., at a flow rate of 15 to 25 m3 per hour, to mix the powders for a period of 10 to 15 minutes;
• (6) adding a granulation liquid in three stages;
• performing a drying stage between each of the granulation stages, and keeping the fluidization conditions without adding liquid;
• and
• (7) compressing the granules obtained in compression machine.