Bioactive fractions and compounds from Dalbergia sissoo for the prevention or treatment of osteo-health related disorders

Patent metadata

Field	Value
Publication number	US-10292994-B2
Application number	US-201214113561-A
Country	US
Kind code	B2
Filing date	Apr 25, 2012
Priority date	Apr 25, 2011
Publication date	May 21, 2019
Grant date	May 21, 2019

Abstract

The present invention relates to bioactive fractions and compounds from Dalbergia sissoo for the prevention or treatment of osteo-health related disorders. The present invention relates in the field of pharmaceutical composition that provides new plant extracts, their fractions and pure compound isolated from natural sources that are useful for the prevention and/or treatment of various medical indications associated with estrogen dependent or independent diseases or syndromes or disorders preferably in the prevention or treatment of estrogen dependent or independent diseases or syndromes or disorders caused in humans and animals, and achievement of peak bone mass during skeletal growth and health in humans and animals. Particularly the present invention further relates to the processes for the preparation of biologically active extracts, fractions, and isolation of pure compounds, from Dalbergia sissoo plant from the family Fabaceae their pharmaceutically acceptable salts and compositions of the principal aspect of the present invention.

First claim

We claim:

1. A method of prevention or treatment of a bone disorder, comprising administering to a subject in need thereof a pharmaceutical composition comprising an osteogenic effective amount of a purified compound of formula 10:

and pharmaceutically acceptable salts thereof, formulated in a tablet or capsule form with at least one pharmaceutically acceptable excipient,
wherein the bone disorder is a disease or condition caused by one or more of osteoporosis, bone loss, failure to achieve optimal bone formation, failure to achieve optimal bone fracture healing, low peak bone mass attainment during skeletal growth, and impaired new bone formation.

2. The method of claim 1 , wherein the purified compound of formula 10 induces a 15-fold increase in bone morphogenic protein (BMP-2) expression in primary calvarial osteoblast cells in rats over that of vehicle-treated rats when administered at 5.0 mg·kg −1 ·day −1 for 3 consecutive days.

3. The method of claim 1 , wherein the purified compound is non-toxic to primary calvarial osteoblast cells in rats when tested at concentration ranging between 1 pM to 1 μM for 48 h.

4. The method of claim 1 , wherein the purified compound induces proliferation of primary calvarial osteoblast cells in rats when tested at a concentration ranging between 1 pM to 1 μM without causing cell growth arrest.

5. A method for prevention or treatment of bone disorders wherein the method comprises the steps of administering to a subject in need thereof a pharmaceutical composition comprising an osteogenic effective amount of a purified compound of formula 10

and pharmaceutically acceptable salts thereof in a tablet or capsule form formulated with a pharmaceutically acceptable excipient selected from one or more of lactose, mannitol, sorbitol, microcrystalline cellulose, sucrose, sodium citrate, and dicalcium phosphate.

6. A pharmaceutical composition comprising an osteogenic effective amount of a purified compound of formula 10,

and pharmaceutically acceptable salts thereof, formulated in a tablet or capsule form.

7. The pharmaceutical composition as claimed in claim 6 , wherein the purified compound exhibits a 15 fold increase when tested for bone morphogenic protein-2 expression in calvaria in rats over that of vehicle-treated rats at a dose of 5.0 mg kg −1 day −1 for 3 consecutive days.

8. The pharmaceutical composition as claimed in claim 6 , wherein the purified compound is nontoxic to rat osteoblasts when tested at concentration ranging between 1 pM to 1 μM for 48 h.

9. The pharmaceutical composition as claimed in claim 6 , wherein the purified compound induces proliferation of neonatal rat calvarial osteoblasts when tested at a concentration ranging from 1 pM to 1 μM without causing cell growth arrest.

10. The pharmaceutical composition as claimed in claim 6 , wherein the purified compound exhibits an osteogenic effect when tested on bone marrow stromal cells at a concentration ranging from 1 mg/kg/day to 5 mg/kg/day.

11. The pharmaceutical composition as claimed in claim 6 , wherein the purified compound is isolated from an n-butanol soluble fraction of an ethanol extract of leaves of a Dalbergia sissoo plant.

12. A pharmaceutical composition comprising a bone anabolically effective amount of a purified compound having formula 10

and pharmaceutically acceptable salts thereof, formulated in a tablet or capsule form with at least one pharmaceutically acceptable excipient.

13. A pharmaceutical composition as claimed in claim 12 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of lactose, mannitol, sorbitol, microcrystalline cellulose, sucrose, sodium citrate, dicalcium phosphate, and combinations thereof.

14. The pharmaceutical composition as claimed in claim 11 , wherein the purified compound is isolated by chromatography from the n-butanol soluble fraction of the ethanol extract of the leaves of the Dalbergia sissoo plant.

Assignees

• Maurya Rakesh
• Dixit Preety
• Trivedi Ritu
• Khedgikar Vikram
• Gautam Jyoti
• Kumar Avinash
• Singh Divya
• Singh Shelendra Pratap
• Wahajuddin
• Jain Girish Kumar
• Chattopadhyay Naibedya
• Council Scient Ind Res

Inventors

• Maurya Rakesh
• Dixit Preety
• Trivedi Ritu
• Khedgikar Vikram
• Gautam Jyoti
• Kumar Avinash
• Singh Divya
• Singh Shelendra Pratap
• Wahajuddin
• Jain Girish Kumar
• Chattopadhyay Naibedya

Classifications

• A61K31/7048 Primary

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• C07D311/36

  not hydrogenated in the hetero ring, e.g. isoflavones · CPC title

• A61P19/10

  for osteoporosis · CPC title

• A61K36/48

  Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae · CPC title

• C07H17/07

  Benzo[b]pyran-4-ones · CPC title