Compositions containing thymohydroquinone and their method of preparation

Patent metadata

Field	Value
Publication number	US-10945969-B2
Application number	US-201816232197-A
Country	US
Kind code	B2
Filing date	Dec 26, 2018
Priority date	Dec 27, 2017
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

Disclosed are compositions enriched with thymohydroquinone, further comprising of thymoquinone, hederagenin and/or α-hederin formulated by blending the active molecules isolated from the seeds of Nigella sativa. Also disclosed are novel processes for the isolation of bioactive components thymohydroquinone, thymoquinone from the seeds of Nigella sativa. A process for the isolation α-hederin and hederagenin from the spent material of Nigella sativa is also disclosed herein.

First claim

We claim:

1. A composition comprising thymohydroquinone as represented by STR#1 isolated from the seeds of Nigella sativa , wherein said composition is standardised to contain 2%-5% w/w thymoquinone, 0.01%-10% w/w thymohydroquinone, 20%-95% w/w fatty acids, 0.001%-3% w/w α-hederin, 0.1%-4.0% w/w rosmarinic acid and 0.2%-2% w/w piperine.

2. The composition as in claim 1 , wherein the composition is prepared using a process comprising steps of:
o) Powdering the seeds of Nigella sativa , pulverizing using 1.5 mm mesh and passing through magnetic separator to obtain a coarse powder;
p) Subjecting the powder of step a) to super critical fluid extraction (SCFE) using liquid CO2 to obtain three fractions: low volatile compounds—S1 fraction, high volatile compounds—S2 fraction and spent residue;
q) Identifying the compounds in low volatile and high volatile fractions as thymoquinone as represented by STR#2, thymohydroquinone as represented by STR#1 and free fatty acids using Gas Chromatography with total yield of about 10-40% in S1 fraction and about 1-6% in S2 fraction respectively;
r) Extracting the spent residue of step b) with 5 volumes of ethanol at 60°−65° C. with stirring for 3 hours;
s) Filtering the concentrating the ethanol extract of step d) to obtain a brownish paste;
t) Dissolving the brownish paste of step e) in water and partitioning thrice with 3 volumes of hexane to obtain aqueous and hexane fractions;
u) Partitioning the aqueous fraction of step f) thrice with n-butanol;
v) Quenching the n-butanol fraction of step g) with water to strip off the solvent while maintaining 20-30% of total dissolved solids;
w) Spray drying to obtain pale brownish powder identified as α-hederin (CAS no. 27013-91-8) represented by STR#3 by HPLC with yield of 0.001-5% on a dry basis;
x) Blending the S2 fraction of step c) with α-hederin of step i) to obtain a mixture comprising thymohydroquinone, thymoquinone, α-hederin and free fatty acids;
y) Dissolving the mixture of step j) with ethanol in a reactor with stirring at 65°-70° C. for 30 minutes to obtain a homogenous mixture;
z) Stripping off the ethanol from mixture of step k) under vacuum and filtering to remove insolubles to obtain a brownish yellow oily liquid;
aa) Adding stabilizing agents (rosmarinic acid) and bioavailability enhancers—pieprine to the mixture of step l)
bb) Formulating the mixture of step m) into tablets, capsules, soft gels, powder, pills, syrups, lozenges, suspension, emulsions.

3. The composition as in claim 1 , wherein the free fatty acids in the compositions comprises of less than 0.5% w/w Ω 3 (omega 3) fatty acids, 40%-70% w/w Ω 6 (omega 6) fatty acids and 15%-25% w/w Ω 9 (omega 9) fatty acids.

Assignees

• Majeed Muhammed
• Nagabhushanam Kalyanam
• Bhat Beena
• Sami Labs Ltd

Inventors

• Majeed Muhammed
• Nagabhushanam Kalyanam
• Bhat Beena

Classifications

• A61K31/05 Primary

  Phenols {(cannabinoids A61K31/658)} · CPC title

• A61K31/122 Primary

  having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K2121/00

  Preparations for use in therapy · CPC title

• G01N21/314

  with comparison of measurements at specific and non-specific wavelengths (dual wavelength spectrometry G01J3/427) · CPC title