Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution...
Reexamination Certificate
2003-09-30
2004-09-28
Henley, III, Raymond J. (Department: 1614)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
Reexamination Certificate
active
06797286
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention.
The present invention is relevant to the field of anti-inflammatories and anti-oxidants and the manufacture of anti-inflammatories and anti-oxidants.
2. Discussion of the Related Art.
The indigenous inhabitants of the Amazon forests refer to plants from the Uncaria species as Uña de Gato (“Cat's claw”). These inhabitants traditionally used the Uncaria plant(s) in a raw unprocessed botanical form as a treatment for a wide array of health disorders. More specifically, ethnomedical preparations of Uncaria plant(s) were and are today consumed as decoctions or teas made from the bark of Uncaria brewed in water. Numerous researchers propose that the Uncaria chemical constituents, and particularly the alkaloids oxindole and pentacyclic, are responsible for its immune enhancing action of the plant material.
Today, Cat's Claw is marketed and sold as an herbal medicine throughout the world. The primary form of these commercial preparations entails the manual manipulation of the bark, root or leaves to produce varying particulate powders. Said powders are then encapsulated for oral administration at a suggested dosage of 1-3 grams of crude material per day. It is not obvious nor has it been taught that these commercial preparations for Uncaria duplicate its historical efficacy. As of this writing, a review of the literature reveals that there has never been a single peer-reviewed scientific article demonstrating any human efficacy or health benefits derived from the oral consumption of the crude plant parts of Uncaria. Furthermore, since the solid matter from teas or decoctions is discarded (e.g. as a tea bag), it is unclear whether this solid matter would in fact cause stomach irritation, toxicity or limit the absorption of Uncaria's active ingredients.
Researchers have identified inherent immunostimulating as well as immunosuppressant actions caused by the diverse chemical constituents of the Uncaria species. Researchers have determined that Uncaria's immunostimulating actions are attributable to alkaloids, pentacyclic and oxindole, that are more lipophilic than the transcriptionally active immunosuppressant components. There is prior and established art for the extraction and concentration of these lipophilic and immunostimulating alkaloids by various methods primarily utilizing alcohol rather than water as the extracting agent.
Related art exists for the extraction, concentration and determination of Uncaria's lipophilic alkaloids extractions with higher alkaloid concentrations (U.S. Pat. Nos. 4844901, 4940725, 5302611, 5723625). The method uses aqueous ammonia pretreatment followed by supercritical extraction. The resultant material has been indicated for unspecific stimulation of the immune system as characterized by increased macrophage phagocytosis.
Related art also exists that teaches that a hot water extraction of the crude plant parts of Uncaria and the subsequent dialysis of the solubilized products yields a composition which has a high degree of the immune stimulatory activities (U.S. Pat. Nos. 6039949, 6238675, 6361805). These activities were confirmed through increased lymphocyte phagocytosis and cytokine production and more recently, increased vaccine response. However, while increased leukocyte phagocytosis and cytokine production are characteristics of the immune response, they contribute to tissue injury during states of inflammation. Thus, current therapeutic approaches in treating inflammatory disorders usually seek to lower cytokine levels and inhibit leukocyte activity.
SUMMARY OF THE INVENTION
Aspects of the invention are summarized below to aid in the understanding of embodiment(s) of the invention and the application. Yet, the invention is fully defined by the claims of the application.
In contrast to its immunostimulating alkaloids, preparations or decoctions of Uncaria plant material also exhibit an inherent immunosuppressive and anti-inflammatory result. This dichotomy between the immunostimulatory (pro-inflammatory) alkaloids and the immunosuppressive (anti-inflammatory) agents, concurrent yet opposing actions—stimulation and suppression—limit the true potential and benefits of either component. Thus, a method of distinguishing and removing from Uncaria decoctions the immunostimulatory alkaloids would result in an Uncaria extract with enhanced efficacy and therapeutic potential of the polar, immunosuppressive, TNF-alpha inhibiting agents. The present invention describes an extract and method for extracting or depleting from plants of the Uncaria species (Cat's Claw or Uño de gato) it's lipophilic, immunostimulating alkaloids whilst retaining and then further concentrating its polar, immunosuppressive agents. The process generally comprises an organic extraction(s) and drying of decocting crude Uncaria plant parts. The resulting Uncaria extract is substantially deplete of immunostimulatory actives and retains enhanced anti-inflammatory components and antioxidant capacities.
The Uncaria extract described herein demonstrates antioxidant activity and also an ability to inhibit the formation of inflammatory and immune mediators like tumor necrosis factor alpha (TNFalpha) by suppressing the activation of genes associated with inflammation and the immune response. This transcriptional inhibition likely results from suppression of nuclear factor kappa B (NF-kB) and functions to suppress an over active immune response that contributes to tissue injury during states of inflammation. It is counterintuitive that the enhancement and concentration of known immunostimulatory (i.e. pro-inflammatory) alkaloids would act as immunosuppressants and exert any anti-inflammatory activity.
This invention demonstrates that the Uncaria extract by the process disclosed herein is characterized by enhanced immunosuppressant and anti-inflammatory action and therefore requires an effective dose twenty times less (i.e. 2 mg/kg) than extracts or decoctions produced by other methods. Anti-inflammatory and transcriptionally acting immune modulating actions of the Uncaria extract preparations described herein have application in disorders characterized by NF-kB activation, oxidant burden, enhanced cytokine production and cell death. These disorders include, but are not limited to, arthritis (both osteoarthritis and rheumatoid), inflammatory bowel disease (IBD), gastritis, chronic inflammation of the eyes, skin, liver, muscles and kidney, fibromyalgia, atherosclerosis, and Alzheimer's disease.
REFERENCES:
patent: 4844901 (1989-07-01), Keplinger et al.
patent: 4940725 (1990-07-01), Keplinger et al.
patent: 5302611 (1994-04-01), Keplinger et al.
patent: 5723625 (1998-03-01), Keplinger et al.
patent: 6039949 (2000-03-01), Pero
patent: 6238675 (2001-05-01), Pero
patent: 6264994 (2001-07-01), Castillo et al.
patent: 6361805 (2002-03-01), Pero
Medical Botany, Lewis et al., published 1977 by John Wiley & Sons (NY), pp 277-279 and 509.*
Mark JS Miller et al., Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis, BMC Comp and Alternative Med Dec. 2001, I:II, U.S.
M. Sandoval et al., Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosaandUncaria guianensis) are indept . . . , Phytomedicine 9:325-337, 2002, U.S.
J Piscoya et al., Efficacy and safety of freeze-dried cat's claw in osteorarthritis of the knee: mechanisms . . . , Inflamm.res.50(2001) 442-448, U.S.
M Sandoval et al., Cat's Claw Inhibits TNalpha Prod. and Scavenges Free Radicals: Role in Cytoprotection, Free Radical Biology & Med, vol. 29 No. 1 pp 71-78,2000, U.S.
R Aquino et al, New quinovic acid glycosides from Uncaria Tomentosa, J Natural Prod, vol. 51, No. 2, pp 257-261, Mar.-Apr. 1998, U.S.
G Konwalinka, Capillary electrophoretic analysis of oxidole alkaloids fromUncaria tomentosa, J of Chromatography, 609 (1992) pp 375-380, U.S.
H Stuppner et al, HPLC Analysis of the Main Oxidole Alkaloids fromUncaria tomentosa, Chromatography, V 34, No 11/12, Dec. 1992, U.S.
G. Laus et al.,
Ellis & Venable P.C.
Henley III Raymond J.
Rainforest Nutritionals, Inc.
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