Milk-derived microvesicle compositions and related methods

Patent metadata

Field	Value
Publication number	US-2016000710-A1
Application number	US-201414770634-A
Country	US
Kind code	A1
Filing date	Feb 26, 2014
Priority date	Feb 26, 2013
Publication date	Jan 7, 2016
Grant date	—

Abstract

A composition is provided that comprises a therapeutic agent encapsulated by a milk-derived microvesicle. The compositions can include therapeutic agents such as phytochemical agents or chemotherapeutic agents, while the milk-derived microvesicle can be derived from raw milk or colostrum. Further provided are methods for isolating a microvesicle that includes the steps of obtaining an amount of milk, and subjecting the milk to a series of sequential centrifugations configured to yield greater than about 300 mg of microvesicle protein per 100 ml of milk. Methods of modifying an immune response and treating a cancer in which a milk-derived microvesicle composition is administered are also provided.

First claim

What is claimed is:

1 . A composition, comprising an effective amount of a therapeutic agent encapsulated by a milk-derived microvesicle.

2 . The composition of claim 1 , wherein the milk-derived microvesicle is a colostrum-derived microvesicle.

3 . The composition of claim 1 , wherein the therapeutic agent is selected from the group consisting of a phytochemical agent and a chemotherapeutic agent.

4 . The composition of claim 3 , wherein the therapeutic agent is a phytochemical agent, and wherein the phytochemical agent is selected from curcumin, demethoxycurcumin, delphinidin, cyanidin, withaferin A, tanshinone, bilberry anthocyanidins, and combinations thereof.

5 . The composition of claim 4 , wherein the therapeutic agent is a bilberry anthocyanidin mixture, punicalagin, withaferin A, or tanshinone.

6 . The composition of claim 3 , wherein the therapeutic agent is a chemotherapeutic agent, and wherein the chemotherapeutic agent is doxorubicin, paclitaxel, docetaxel, or a combination thereof.

7 . The composition of claim 1 , further comprising one or more miRNA molecules in the milk-derived microvesicle.

8 . The composition of claim 7 , wherein the one or more miRNA molecules are selected from the group consisting of miR-155 and miR-223.

9 . A pharmaceutical composition, comprising a composition according to claim 1 and a pharmaceutically-acceptable vehicle, carrier, or excipient.

10 . A method for isolating a microvesicle, comprising:
obtaining an amount of milk; and subjecting the milk to a series of sequential centrifugations configured to yield greater than about 300 mg of microvesicles protein per 100 ml of milk.

11 . The method of claim 10 , wherein the milk is raw milk.

12 . The method of claim 10 , wherein the milk is colostrum.

13 . The method of claim 10 , wherein the series of sequential centrifugations comprises:
a first centrifugation at 20,000×g at 4° C. for 30 min; a second centrifugation at 100,000×g at 4° C. for 60 min; and a third centrifugation at 120,000×g at 4° C. for 90 min.

14 . The method of claim 10 , further comprising the step of storing the isolated microvesicles at a concentration of about 5 mg/ml to about 10 mg/ml.

15 . A method of modifying an immune response, comprising administering to a subject in need thereof an effective amount of a composition including a therapeutic agent encapsulated by a milk-derived microvesicle.

16 . The method of claim 15 , wherein the therapeutic agent is selected from a phytochemical agent and an miRNA.

17 . The method of claim 16 , wherein the therapeutic agent is a phytochemical agent, and wherein the phytochemical agent is selected from curcumin, demethoxycurcumin, delphinidin, cyanidin, withaferin A, tanshinone, bilberry anthocyanidins, and combinations thereof.

18 . The method of claim 16 , wherein the therapeutic agent is a miRNA, and wherein the miRNA is selected from the group consisting of miR-155 and miR-223.

19 . The method of claim 15 , wherein administering the composition reduces an amount of an inflammatory cytokine in a subject.

20 . The method of claim 19 , wherein the inflammatory cytokine is selected from the group consisting of tumor necrosis factor-α, interleukin-1β, interferon γ, and interleukin-6.

21 . The method of claim 15 , wherein administering the composition reduces an amount of NF-κB signaling in a subject.

22 . The method of claim 15 , wherein administering the composition comprises orally, intravenously, intranasally, or intraperitoneally administering the composition.

23 . A method of treating a cancer in a subject, comprising administering to a subject in need thereof an effective amount of a composition including a milk-derived microvesicle.

24 . The method of claim 23 , wherein the composition includes a therapeutic agent encapsulated by the milk-derived microvesicle

25 . The method of claim 23 , wherein the cancer is selected from the group consisting of breast cancer, uterine cancer, lung cancer, prostate cancer, ovarian cancer, cervical cancer, and pancreatic cancer.

26 . The method of claim 23 , wherein the therapeutic agent is selected from the group consisting of a phytochemical agent and a chemotherapeutic agent.

27 . The method of claim 26 , wherein the therapeutic agent is a phytochemical agent, and wherein the phytochemical agent is selected from curcumin, demethoxycurcumin, delphinidin, cyanidin, withaferin A, tanshinone, bilberry anthocyanidins, and combinations thereof.

28 . The method of claim 26 , wherein the therapeutic agent is a chemotherapeutic agent, and wherein the chemotherapeutic agent comprises doxorubicin, paclitaxel, docitaxel, or combinations thereof.

29 . The method of claim 23 , further comprising one or more miRNA molecules in the milk-derived microvesicle.

30 . The method of claim 29 , wherein the one or more miRNA molecules are selected from the group consisting of miR-155 and miR-223.

31 . The method of claim 23 , wherein administering the composition comprises orally, intravenously, intranasally, or intraperitoneally administering the composition.

Assignees

• Univ Louisville Res Found

Inventors

• Gupta Ramesh C
• Munagala Radha
• Aqil Farrukh
• Jeyabalan Jeyaprakash

Classifications

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title

• A61K9/5176

  Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/5123) · CPC title

• A61K31/7042

  Compounds having saccharide radicals and heterocyclic rings · CPC title

• A61K31/12

  Ketones · CPC title

• A61K31/585

  containing lactone rings, e.g. oxandrolone, bufalin · CPC title