Pharmaceutical composition for the treatment of diminution of bone tissue

Patent metadata

Field	Value
Publication number	US-10596115-B2
Application number	US-201414904981-A
Country	US
Kind code	B2
Filing date	Jul 16, 2014
Priority date	Jul 17, 2013
Publication date	Mar 24, 2020
Grant date	Mar 24, 2020

Abstract

A method for prevention and/or treatment of diminution of bone tissue using a composition comprising a compound selected from Withaferin A (WFA), Withanolide A, and Withanone. The composition showed enhanced WFA bioavailability in rodents against plain WFA, promotes bone marrow cell differentiation, and increases the percent of bone volume to tissue volume (BV/TV %) by 3 folds as compared to free Withaferin A (WFA).

First claim

We claim:

1. A method of treating diminution of bone tissue occurring due to osteoporosis, estrogen loss, aging, or drug induction, wherein the method comprises:
administering to a subject in need thereof liposomes comprising Withaferin A in a concentration in the range of 0.1 to 0.5% w/v, glycol chitosan in a concentration in the range of 0.1 to 0.2% w/v, and distearoylphosphatidylcholine (DSPC), soya phosphatidylcholine (Soya PC), and cholesterol in the molar ratio of 7:3:3, wherein the liposomes are coated with the glycol chitosan; and
wherein the liposomes induce osteogenic effect into mammalian bone tissue; and
wherein the diminution of bone tissue is not caused by arthritis.

2. The method of treating diminution of bone tissue of claim 1 , wherein the Withaferin A was obtained from Withania Somnifera.

3. The method of treating diminution of bone tissue of claim 1 , wherein the liposomes comprise the Withaferin A in a concentration of 0.1% w/v.

4. The method of treating diminution of bone tissue of claim 1 , wherein the liposomes are coated with the glycol chitosan in a concentration of 0.2% w/v.

5. The method of treating diminution of bone tissue of claim 1 , wherein the liposomes comprise the Withaferin A in a concentration of 0.5% w/v.

6. The method of treating diminution of bone tissue of claim 1 , wherein the liposomes additionally comprise a non-ionic surfactant.

7. The method of treating diminution of bone tissue of claim 6 , wherein the non-ionic surfactant is selected from the group consisting of Tween-20, Tween-40, Tween-60, Tween-80, Span 40, Span 60, Span 80, and Cremophor.

8. A process for the preparation of the liposomes as claimed in claim 1 , wherein the process comprises:
(i) preparing a solution of the Withaferin A and the DSPC, Soya PC, and cholesterol in a solvent followed by evaporation of the solvent under reduced pressure to form a thin film;
(ii) keeping the film obtained in (i) under vacuum up to 12 hrs and hydrating the film with PBS buffer at a pH in the range of 7.2 to 7.4 to obtain multilayered lipid vesicles;
(iii) sequentially extruding the multilayered lipid vesicles obtained in (ii) through 400 nm, 200 nm, and 100 nm filter for 15 cycles to obtain a uniform population of vesicles;
(iv) coating the uniform population of vesicles of (iii) with the 0.1 to 0.2% w/v glycol chitosan (GC) to obtain liposomes; and
(v) dispersing the liposomes of (iv) in 0.2% w/v GC solution for 10 min under stirring to obtain a pharmaceutical composition.

9. The process as claimed in claim 8 , wherein the solvent of (i) is selected from the group consisting of chloroform, ethanol, and mixture thereof.

10. The process for preparation of the liposomes as claimed in claim 8 , wherein the Withaferin A was obtained from Withania Somnifera.

11. A method of treating diminution of bone tissue occurring due to osteoporosis, estrogen loss, aging, or drug induction, wherein the method comprises:
administering to a subject in need thereof liposomes comprising Withaferin A in a concentration of 0.5% w/v, glycol chitosan in a concentration of 0.2% w/v, and distearoylphosphatidylcholine (DSPC), soya phosphatidylcholine (Soya PC), and cholesterol in the molar ratio of 7:3:3, wherein the liposomes are coated with the glycol chitosan; and
wherein the liposomes induce osteogenic effect into mammalian bone tissue; and
wherein the diminution of bone tissue is not caused by arthritis.

Assignees

• Council Scient Ind Res

Inventors

• Trivedi Ritu
• Mishra Prabhat Ranjan
• Singh Divya
• Khedgikar Vikram
• Kushwaha Priyanka
• Adhikary Sulekha
• Choudhary Dharmendra
• Gautam Jyoti
• Kumar Avinash
• Karvande Anirudha
• Verma Ashwni
• Sharma Shweta
• Trivedi Prabodh K
• Sangwan Neelam S
• Sangwan Rajender S

Classifications

• A61K31/585

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

• A61P19/10

  for osteoporosis · CPC title

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title