Methods and compositions for controlled delivery of phytochemical agents

• US 8,858,995 B2
• Filed: 03/26/2012
• Issued: 10/14/2014
• Est. Priority Date: 03/10/2008
• Status: Active Grant

• Current Assignee: University of Louisville
• Original Assignee: University of Louisville
• Inventors: Gupta, Ramesh C., Vadhanam, Manicka V., Aqil, Farrukh
• Primary Examiner(s): Desai, Anand
• Assistant Examiner(s): MERCIER, MELISSA S
• Application Number:
  US13/429,601
• Publication Number:
  US 20120231079A1
• Time in Patent Office: 932 Days
• Field of Search: None
• US Class Current: 424/469
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/01 Hydrocarbons
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/121 acyclic
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 36/235 Foeniculum (fennel)
• CPC Class Codes: A61K 36/82 Theaceae (Tea family), e.g. camellia
• CPC Class Codes: A61K 36/9066 Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Compositions are provided that comprises a biocompatible polymeric matrix incorporating an effective amount of a phytochemical agent, a combination of phytochemical agents, or a phytochemical agent and one or more additional therapeutic agents. Methods of treating a cancer using the compositions are further provided.

Claims

1. A composition, comprising:

a biocompatible polymeric matrix incorporating an effective amount of a phytochemical agent; and

a polymeric coating surrounding the biocompatible polymeric matrix,

wherein the composition releases a controlled low dose of the phytochemical agent over a time period, and

wherein the polymeric coating is comprised of polycaprolactone.

2. The composition of claim 1, wherein the time period is at least about 18 months.

3. The composition of claim 1, wherein the biocompatible polymeric matrix is comprised of a polymer selected from the group consisting of polycaprolactone, cyclodextrin, F68, polyethylene glycol, and combinations thereof.

4. The composition of claim 1, wherein the biocompatible polymeric matrix comprises polycaprolactone in combination with a second polymer.

5. The composition of claim 4, wherein the second polymer is selected from the group consisting of cyclodextrin, F68, and polyethylene glycol.

6. The composition of claim 4, wherein the polycaprolactone and the second polymer are combined in a ratio of about 4:

1 or about 9;

1.

7. The composition of claim 1, wherein the biocompatible polymeric matrix comprises polycaprolactone and F68 in a ratio of about 4:

1.

8. The composition of claim 1, wherein the biocompatible polymeric matrix comprises polycaprolactone and polyethylene glycol in a ratio of about 65:

35.

9. The composition of claim 1, wherein the phytochemical agent is curcumin.

10. The composition of claim 1, wherein the biocompatible polymeric matrix is biodegradable.

11. The composition of claim 1, wherein the phytochemical agent comprises about 2% to about 50% of the polymer weight.

12. The composition of claim 1, wherein the phytochemical agent is selected from the group consisting of curcumin, green tea polyphenols, punicalagin, diindolylmethane, oltipraz, tocotrienol, tocopherol, plumbagin, cyanidin, delphinidin, lycopene, lupeol, curcurbitacin-B, Withaferin A, indole-3-carbinol, genestein, equol, resveratrol, co-enzyme Q-10, ellagic acid, petunidin, malvidin, peonidin, fennel extract, and combinations thereof.

13. The composition of claim 1, wherein the phytochemical agent is a combination of:

oltipraz and curcumin;

curcumin, ellagic acid, co-enzyme Q-10, and lycopene;

curcumin, green tea polyphenols, diindolylmethane, and punicalagin;

delphinidin, petunidin, malvidin, peonidin, and cyanidin;

or

punicalagin and delphinidin.

14. The composition of claim 13, further comprising a second biocompatible polymeric matrix, wherein the second biocompatible polymeric matrix incorporates at least one phytochemical agent.

15. The composition of claim 1, further comprising an effective amount of an anti-inflammatory agent incorporated into the biocompatible polymeric matrix or a second biocompatible polymeric matrix.

16. The composition of claim 1, further comprising an effective amount of a chemotherapeutic agent incorporated into the biocompatible polymeric matrix or a second biocompatible polymeric matrix.

17. The composition of claim 1, wherein the polymeric coating comprises one or more layers.

18. The composition of claim 17, wherein the one or more layers comprise about 5 to about 40 layers.

19. The composition of claim 1, wherein the biocompatible polymeric matrix is in the form of a coating.

20. The composition of claim 19, wherein the coating comprises about 20 to about 40 layers.