Link: Pharm/Biotech Resources
United States Patent: 6,896,901
Issued: May 24, 2005
Inventors: Pratap; Ram (Lucknow, IN); Pal; Raghwendra (Lucknow, IN); Singh; Satyawan (Lucknow, IN); Shankar; Girja (Lucknow, IN); Nath; Chandeshwar (Lucknow, IN); Singh; Hemant Kumar (Lucknow, IN); Raina; Depak (Lucknow, IN); Srivastava; Arwind Kumar (Lucknow, IN); Rastogi; Anil Kumar (Lucknow, IN); Murthy; Puvvada Sri Ramachandra (Lucknow, IN); Srivastava; Sudhir (Lucknow, IN); Asthana; Onkar Prasad (Lucknow, IN); Singh; Narenda (Lucknow, IN); Nand; Nitya (Lucknow, IN)
Assignee: Council of Scientific & Industrial Research (IN)
Appl. No.: 742424
Filed: December 22, 2000
The present invention provides new uses of Gugulipid, an ethyl acetate extract of the resin of the plant Comiphora wighitii, for controlling or preventing cognitive dysfunction, hyperglycemia and some infective conditions of the skin and a method of preparing Gugulipid by agitating the resin in shake flask assembly or sonicating assembly and preparing a solid or a creamy dosage forms.
Description of the Invention
FIELD OF INVENTION
The present invention claims some new uses of Gugulipid, an ethyl acetate extract of the resin of the plant Comiphora wighitii, commonly called gum guggulu. These include modifications of the extraction methods and methods for controlling or preventing cognitive dysfunction, hyperglycemia and some infective conditions of the skin.
BACKGROUND OF THE INVENTION
Ayurveda takes a holistic view of human disease. It views any disease as a dysfunction of the whole body rather than of a single organ or physiological process. Most of the Ayurvedic drugs therefore are likely to act on a number of dysfunctions of the body involving a number of organs and functions. Gugulipid, an ethylacetate soluble fraction of gum guggul, was developed as a hypolipidemic agent, based on the reference to the lipid lowering effect of guggul resin in Charak Samhita, a classic text of Ayurveda. Chemopharmacological investigation of this extract resulted in the characterization of guggulsterone [cis-and trans-4, 17 (20)-pregnadiene-3, 16-dione] as the major constituent. Apart from guggulsterone, other chemical constituents in the ethyl acetate soluble fraction added to and modulated the total activity. This fraction rather than pure guggulsterone was developed as a hypolipidemic drug and named gugulipid. As a follow up of the holistic view of Ayurveda of human disease, gugulipid was tested for other related and unrelated conditions/dysfunction and found to possess cognitive and anti-hyperglycemic activities and also improved in general dermal dysfunctions. These novel uses of gugulipid are now claimed.
Guggul, highly valued in Indian system of medicine Ayurveda, is the gum
resin exudate of a small tree Commiphora wighitii belonging to the
family Burseraceae. It is specially recommended for the treatment of
obesity, lipid disorders and rheumatoid arthritis (Ayurvedic treatise:
Sushruta, Vagabhatta). In Tibetan medicine, the plant (C. Wighitii)
mixed with other herbs is used for skin diseases, anemia, edema, salivation
and heaviness of stomach [Lama, S. and Santra, S. C., Sci. Cult. 45,
262 (1979)]. Modern pharmacological studies on the crude drug and some of
its fractions have supported the claims of Ayurveda. The anti-arthritis and
anti-inflammatory activities were confirmed by Gujral and co-workers [Gujral,
M. L., Sareen, K., Tangri, K. K., Amma, M. K. P. and Roy, A. K. Ind. J.
Physiol. Pharmacol. 4, 267 (1960)]. The hypolipidemic and
anti-atherosclerotic activities reported by Dwarakanath and Satyawati. [Dwarakanath,
C., and Satyawati, G. V. Ayurveda Pradeepika (Ceylon), 1, 69 (1970)];
Satyawati, G. V. in "Effect of an indigenous drug and disorders of lipid
metabolism with special reference to atherosclerosis and obesity (Medoroga)",
M.D. Thesis (Doctor of Ayurvedic Medicine), Banaras Hindu University,
Varanasi, (1966)]. Later on, its ethyl acetate extract was developed by
joint efforts of Malti-Chem Research Center, Baroda and Central Drug
Research Institute, Lucknow as hypolipidemic drug [A process for obtaining
hypolipidemic and anti-platelet aggregation fraction from guggul resin.
Indian Patent No.148265 dated 6.4.79., N. K. Kapoor., Sukh Dev and S.
Nityanand]. A mixed type of mechanism has been implicated for lipid lowering
effect of gugulipid. The stimulation of plasma LCAT, hepatic lipases,
receptor mediated catabolism of LDL and increased faecal bile acid excretion
as well as suppression of hepatic cholesterol biosynthesis are the
mechanisms responsible for lipid lowering effect of gugulipid [S. Nityanand
and N. K. Kapoor, Ind J. Exp. Biol. 11, 395 (1973); N. K. Kapoor and
S. Nityanand, Ind. J. Heart Res. Supp-1) 22 (1988)]. With the
discovery of hypolipidemic activity of the gum resin, systematic chemical
investigations were carried out to characterize compounds of the gum resin
responsible for hypolipidemic activity. Mc Cook et al. have recently claimed
alcoholic extract of gum guggul for controlling or preventing sebum
secretion from sebocytes which is associated with a shiny, undesirable
appearance and a disagreeable tactile sensation [J. P. Mc Cook et. al. U.S.
Pat. No. 5,690,948 (1997). Antisebum and antioxidant compositions containing
gugulipid and alcoholic fractions thereof].
GENESIS OF THE INVENTION
With the isolation of variety of compounds of varied structural classes such as lignans, lipids, diterpenoids and steroids, we initiated quite early a program to investigate structure based biological profiles of gugulipid. Earlier, it was revealed that the hypolipidemic and thyroid stimulating actions of guggulsterone [Tripathi, S. N., Gupta, M. Dwivedi, L. D. and Sen, S. P., J. Res. Ind. Med. 10, 11 (1975); Singh, V. and Kapoor, N. K. in "Stimulation of low density lipoprotein receptors activity in liver membrane of guggulsterone treated rats." In Proceedings of Society of Biological Chemists, India, 57th Annual Meeting, CSIR Center for Biochemicals, New Delhi, Oct. 9-12, 1988].
ROLE IN IMPROVING COGNITIVE FUNCTIONS
Recent developments in understanding of neurosteroids, role of free radicals and antioxidants in brain function as well as in hyperglycemia prompted us to explore gugulipid for these activities. Behavioral studies have suggested a potential role of pregnenolone, in particular, for memory enhancement. Intracerebroventricular (i.c.v.) administration of pregnenolone and pregnenolone sulfate leads to an amelioration in various memory task in rodents [Flood, J. F., Morley, J. F., and Robert, E., Memory enhancing effects in male mice of pregnenolone and of steroids metabolically derived from it; Proc. Natl. Acad Sci. USA; 89, 1567 (1992)]. These memory-enhancing effects might be attributed to the N-methyl-D-aspartate (NMDA)-antagonistic properties of pregnenolone sulfate since NMDA agonists have been shown to impair cognitive functions in rodents [Bowlby, M. R., Pregnenolone sulfate potentiation of N-methyl-D-aspartate receptor channels in hippocampal neurons. Mol. Pharmacol., 43, 813 (1993)]. As already stated, cholesterol is the precursor of neurosteroid pregnenolone. These findings prompted us to explore memory enhancing properties of gugulipid because of similarity among biogenic precursor of pregnenolone (1) and steroids present in Gugulipid such as guggulsterol-I (2), guggulsterol-II (3) and guggulsterol-III (4) (FIG. 1) [V. D. Patil, U. R. Nayak and Sukh Dev: Chemistry of Ayurvedic Crude Drugs-I, Tetrahedron 28, 2341 (1972)].
ROLE IN IMPROVEMENT OF DIABETIC CONDITION
Recent years have seen increasing interest in the role of free radical
oxidative damage in human disease. Free radicals are highly reactive species
that have the potential to oxidize biological molecules including proteins,
lipids and DNA. To prevent or retard oxidation, rich arrays of natural
antioxidant mechanism exist. These antioxidant defense mechanisms have been
found defective in many diseases. Increased production of free radicals has
been strongly implicated in the pathophysiology of diabetes and
atherosclerosis. Glucose combines with serum proteins and lipoproteins in a
non-enzymatic glycation reaction and may auto-oxidize in situ generating
free radicals and causing local oxidative damage [Hunt, J. V., Wolff, S. P.
in "Oxidative glycation and free radical production; a causal mechanism of
diabetic complications". Free Radical. Res. Commun. 12-13,115
(1991)]. The free radical scavenging antioxidants react preferentially with
free radicals before vital structure can be attacked.
OBJECTS OF THE PRESENT INVENTION
An object of the present invention was to develop a method of extraction
of Guggul resin by continuous shaking or sonication procedure to obtain
improved yields of the extract. Another object of the present invention was
to develop cognition enhancing effect of gugulipid orally in any
SUMMARY OF THE INVENTION
The present provides process for extraction gugulipid of resin from
aerial branches of the plant C. wighitii comprises suspending
gum/resin with a non-polar solvent, filtration or decantation, repetition of
the process for extraction of fatty acids, extraction of residual matter
with ethyl acetate by continuous shaking or sonication procedure, mixing of
polar and nonpolar fractions and filtration to remove solid suspension and
finally the solvent is removed to get gugulipid.
DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention provides process for extraction gugulipid of resin from aerial branches of the plant C. wighitii, said process comprising
Claim 1 of 5 Claims
1. A method of treating a cognitive memory dysfunction in a mammal, said
method comprising administering to said mammal a pharmaceutically
acceptable composition consisting essentially of a capsule or a tablet of
a memory enhancing effective amount of gugulipid, starch, microcrystalline
cellulose at a yield of 45-60%,