Inhibition of hypoxia-inducible factor activity with Carica papaya extracts

• US 9,789,144 B2
• Filed: 03/13/2014
• Issued: 10/17/2017
• Est. Priority Date: 03/14/2013
• Status: Expired due to Fees

• Current Assignee: Universiti Putra Malaysia (Government of Malaysia), Regents of the University of California (University of California)
• Original Assignee: Universiti Putra Malaysia (Government of Malaysia), Regents of the University of California (University of California)
• Inventors: Stanbridge, Eric J., Shafee, Norazizah, Yusoff, Khatijah
• Primary Examiner(s): Tate, Chris R
• Application Number:
  US14/208,524
• Publication Number:
  US 20140271823A1
• Time in Patent Office: 1,314 Days
• Field of Search: 424774
• CPC Class Codes: A61K 2236/00 Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
• CPC Class Codes: A61K 2236/33 involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 36/185 Magnoliopsida (dicotyledons)

Abstract

An extract of Carica papaya leaves obtained from a plant of age six months and younger from the date of germination of the seed is used as an inhibitor of HIF to effectively block hypoxia-inducible factor (HIF) function and methods of use thereof. More specifically it relates to the use of the Carica papaya plant extract to eliminate unwanted cells by inhibiting HIF in the prevention and treatment of hypoxia-related conditions and diseases such as inflammatory diseases, vascular diseases, cancer and infectious diseases. In a particular embodiment, a solid hypoxic tumor in a patient is treated by administering to the patient a therapeutically acceptable amount of an extract of Carica papaya leaves obtained from a plant of age six months and younger from the date of germination of the seed, preferably an alcohol extract such as a methanol extract, whereby to inhibit hypoxia-inducible factors in the tumor.

Claims

1. A method for treating a solid hypoxic tumor in a patient, the tumor having hypoxia-inducible factors, comprising

administering to the patient a therapeutically effective amount of an extract of Carica papaya leaves obtained from a plant of age six months and younger from the date of germination of the seed, to thereby inhibit the hypoxia-inducible factors.

2. The method of claim 1 wherein the Carica papaya leaves are extracted with an alcohol.

3. The method of claim 2 in which the alcohol is monohydric, polyhydric, unsaturated aliphatic, or alicyclic.

4. The method of claim 2 in which the alcohol is methanol.

5. The method of claim 1 wherein the subject is not otherwise indicated for treatment with the extract of Carica papaya leaves.

6. The method of claim 1 wherein the extract is formulated as a liposome, incorporated into a polymer release system, or suspended in a liquid in a dissolved form or as a colloidal form.

7. The method of claim 1 wherein the extract is administered in combination with a chemotherapeutic agent.

8. The method of claim 7 wherein the chemotherapeutic agent is cisplatin.

9. The method of claim 7 wherein the chemotherapeutic agent is chetomin.

10. The method of claim 7 wherein the patient is treated with a pharmacon comprising said extract and a chemotherapeutic agent.