Polypharmaceutical drug compositions and related methods

Abstract

Disclosed are compositions and methods for treating or ameliorating the symptoms of cancer (e.g., oral cancer) by using a poly-pharmaceutical drug, whose composition consists of relationally optimized ratios of bioactive compounds to enhance their pharmacological characteristics.

1 . A pharmaceutical composition comprising: (a) one or more high polarity compounds isolated from  Curcuma longa  selected from the group consisting of peptides, polysaccharides, and proteins; (b) one or more medium polarity compounds isolated from  Curcuma longa  selected from the group consisting of polyphenols, curcumin, demethoxycurcumin, and bisdemethoxycurcumin; and (c) one or more non-polar compounds isolated from  Curcuma longa  selected from the group consisting of terpenoids, ar-turmerone, α-turmerone, and β-turmerone; wherein the composition comprises a ratio of the high polarity compounds, medium polarity compounds and non-polar compounds selected from the group consisting of about [1]:[1]:[1] by weight and about [3]:[6]:[1] by weight. 
     
     
         2 . The composition of  claim 1 , wherein the one or more high polarity compounds are isolated from  Curcuma longa  using a high polarity solvent system having a dielectric constant of greater than about 25 and a relative polarity value of less than about 0.6. 
     
     
         3 . The composition of  claim 1 , wherein the one or more medium polarity compounds are isolated from  Curcuma longa  using a medium polarity solvent system having a dielectric constant of about 5 to about 25 and a relative polarity value of about 0.25 to about 0.6. 
     
     
         4 . The composition of  claim 1 , wherein the one or more non-polar compounds are isolated from  Curcuma longa  using a non-polar solvent system having a dielectric constant of less than about 5 and a relative polarity value of less than about 0.2. 
     
     
         5 . A method of treating cancer or a pre-cancerous condition, the method comprising administering an effective amount of the composition of  claim 1  to a subject in need thereof, thereby treating the cancer or pre-cancerous condition. 
     
     
         6 . The method of  claim 5 , wherein the cancer is oral squamous cell carcinoma. 
     
     
         7 . The method of  claim 5 , wherein the pre-cancerous condition is leukoplakia. 
     
     
         8 . The method of  claim 5 , wherein the composition is administered in combination with a chemotherapy or immunotherapy agent. 
     
     
         9 . The method of  claim 8 , wherein the immunotherapy agent is selected from the group consisting of checkpoint inhibitors, checkpoint blockers, vaccines and CAR-T cells. 
     
     
         10 . The method of  claim 8 , wherein the composition promotes or increases T-cell infiltration in a tumor of the subject. 
     
     
         11 . The method of  claim 8 , wherein the composition increases sensitivity of a tumor to the chemotherapy or immunotherapy agent. 
     
     
         12 . A composition for use in treating oral squamous cell carcinoma, wherein the compositions comprises:
 a. one or more high polarity compounds isolated from  Curcuma longa  selected from the group consisting of peptides, polysaccharides, and proteins;   b. one or more medium polarity compounds isolated from  Curcuma longa  selected from the group consisting of polyphenols, curcumin, demethoxycurcumin, and bisdemethoxycurcumin; and   c. one or more non-polar compounds isolated from  Curcuma longa  selected from the group consisting of terpenoids, ar-turmerone, α-turmerone, and β-turmerone;   wherein the composition comprises a ratio of the high polarity compounds, medium polarity compounds and non-polar compounds selected from the group consisting of about [1]:[1]:[1] by weight and about [3]:[6]:[1] by weight.   
     
     
         13 . The composition of  claim 12 , wherein the one or more high polarity compounds are isolated from  Curcuma longa  using a high polarity solvent system having a dielectric constant of greater than about 25 and a relative polarity value of less than about 0.6. 
     
     
         14 . The composition of  claim 12 , wherein the one or more medium polarity compounds are isolated from  Curcuma longa  using a medium polarity solvent system having a dielectric constant of about 5 to about 25 and a relative polarity value of about 0.25 to about 0.6. 
     
     
         15 . The composition of  claim 12 , wherein the one or more non-polar compounds are isolated from  Curcuma longa  using a non-polar solvent system having a dielectric constant of less than about 5 and a relative polarity value of less than about 0.2. 
     
     
         16 . The composition of  claim 12 , wherein the composition is formulated for oral administration to a subject. 
     
     
         17 . The composition of  claim 12 , wherein the composition is formulated for buccal administration to a subject. 
     
     
         18 . The composition of  claim 12 , wherein the composition is formulated for transdermal administration. 
     
     
         19 . The composition of  claim 12 , wherein the composition comprises about 11-15% w/w of the high polarity polysaccharides, about 41-44% w/w of the medium polarity compound curcumin, and about 3-4% w/w of the non-polar compound ar-tumerone. 
     
     
         20 . The composition of  claim 12 , wherein upon administration to a subject the composition promotes or increases T-cell infiltration in a tumor of the subject.