Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from vitis
Reexamination Certificate
2001-03-30
2002-08-27
Weber, Jon P. (Department: 1651)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
Containing or obtained from vitis
C424S404000, C424S725000
Reexamination Certificate
active
06440471
ABSTRACT:
TECHNICAL FIELD
The invention relates to plant extracts having therapeutic and other uses, and more particularly to extracts of Vitaceae and Ericaceae families.
BACKGROUND
Analysis of the anti-bacterial adhesion fraction of cranberries and other species has been fruitful of late. For instance, the instant inventors, Edward B. Walker, Richard A. Mickelsen, Jr. and Jennifer N. Mickelsen have previously published their findings regarding the active anti-bacterial fraction in U.S. Pat. Nos. 5,525,341, 5,646,178, 5,650,432, and 5,474,774, the contents of all of which are incorporated by this reference in their entirety.
Similarly, later work was evidently conducted at Rutgers University in an attempt to isolate an active fraction of cranberry and other species. See, e.g., Howell et al. “Inhibition of P-fimbriated
Escherichia coli
to Uroepithelial Cell Surfaces by Proanthocyanidin Extracts from Cranberries”,
New England Journal of Medicine,
339(15):1085-6 (Oct. 8, 1998), and International Application No. PCT/US98/18267, published within a year hereof on Mar. 18, 1999.
As described in the foregoing patents and publications, proanthocyanidins are polyphenolic molecules found in fruits, berries and other plant material. These molecules belong to the flavanoid family of compounds. The flavanoid polyphenolics include the catechins, anthocyanins and proanthocyanidins. Proanthocyanidins are also known in the industry as leucoanthocyanins, leucodelphinins, leucocyanins, anthocyanogens, epicatechin-catechin polymers or procyanidins.
DISCLOSURE OF THE INVENTION
The invention includes compounds isolated from plant materials, particularly plants of the genus Vaccinium, which have biological activity measurable as inhibition of adhesion of bacteria to surfaces, and an extract of such plant materials which is significantly enriched for anti-adhesion activity. Other preferred plants include members of the Vitaceae family, particularly of the Vitus genus. The specific compounds include procyanidins (also known as “condensed tannins”), leukocyanin and leucodelphinin, and flavonol glucosides including myricetin-3-pyranoside. An exemplary, preferredprocyanidin compound is a substituted epicatechin-catechin dimer.
The present invention is further directed to proanthocyanidin extracts. Specifically, a peak of 95 ppm on a
13
C NMR spectrum is found in these proanthocyanidin compositions which is an inherent characteristic of the Howell compounds illustrating an A type linkage. These extracts may be free of tannins, lipids, carbohydrates, simple sugars, protein and amino acids and organic acids as well as being substantially free of anthocyanins. Additionally, these proanthocyanidin extracts are capable of inhibiting agglutination reactions of P-type
E. coli
. As noted, the proanthocyanidin extracts contain at least one A-type interflavanoid bond.
When the extract is analyzed by reverse-phase HPLC on a C18 lipophilic column, characteristic sets of elution peaks of compounds absorbing at 230 nm, 280 nm and 360 nm are observed. When subjected to farther purification, one of the 280 nm-absorbing peaks is found to contain the exemplary procyanidin. The flavonol glucosides are purified from 360 nm-absorbing elution peaks. The pyranoside moiety in these compounds may be glucose, mannose, or a like sugar.
The invention also includes a method of making an extract having the properties outlined in the preceding paragraphs, and a method of inhibiting the adhesion of bacteria to surfaces using the extract.
In another embodiment of the present invention, the extract having the properties previously described, for example, the peak at 95 ppm on the
13
C NMR spectrum, can be used to inhibit P-type
E. coli
, but are incapable of inhibiting agglutination of type 1
E. coli.
In another embodiment, the proanthocyanidin composition of the invention can be administered as a pharmaceutical composition. The pharmaceutical composition includes the proanthocyanidin extract and a pharmaceutically acceptable carrier such as lactose, cellulose, or equivalent, or contained within a pharmaceutical dosage such as a capsule or tablet.
Another aspect of the invention relates to methods of preventing or treating urogenital infections in a mammal by administering a proanthocyanidin composition including the proanthocyanidin extract, a proanthocyanidin compound, a proanthocyanidin polymer or a mixture thereof, to the mammal in an amount and for a time sufficient to prevent, reduce or eliminate the symptoms associated with such infections and thereby lead to an amelioration or curing of the infection. Preferably, the mammal undergoing treatment is human, but the method is also applicable to animals, such as mink.
In another embodiment, the proanthocyanidin composition of the invention can be used to reduce the pathogenesis of P-type
E. coli
found in the digestive tracts of animals such as mink and other mammals.
A further aspect of the invention relates to methods of reducing the incidence of infection after surgery, treating topical wounds and acne, and preventing or eliminating oral infections using the proanthocyanidin composition of the invention.
The invention further embraces compositions produced by first extracting non-active compounds from plant materials with, for example, a solvent, leaving a pulp or residue enriched for the anti-adhesion active fraction. This pulp or residue may be further processed by acid solubilization followed by selected steps as described in the preceding paragraphs, to further enrich for the active fraction. (See, e.g., FIG.
1
).
The extract's anti-adhesion property is useful in a number of areas, for example, in the cleaning of industrial fermentation equipment, medical and dental instruments, medical dressings, laboratory culture jars, and the like. The extract may further have usefulness to inhibit the adhesion of bacteria to surgical implants, to tooth surfaces and oral cell types found in the mouth, and to cells in the urinary tract of humans and/or animals.
A method of inhibiting the adhesion of bacteria includes the steps of providing the described extract, applying the extract in a suitable medium to a surface having bacteria such as
E. coli
adhered thereto and disengaging the bacteria from the surface. The method is useful to inhibit the adhesion of bacteria to such surfaces as teeth, other bacteria adhered to teeth, to human oral epithelial cells, human epithelial urinary tract cells; and to clean dental implants, bacterial fermentation vats, and the like.
REFERENCES:
patent: 3963700 (1976-06-01), Philip
patent: 4083779 (1978-04-01), Combe et al.
patent: 4309207 (1982-01-01), Devlin
patent: 4652448 (1987-03-01), Sadowski
patent: 4775477 (1988-10-01), Stahl, et al.
patent: 4857327 (1989-08-01), Virdalm
patent: 5128100 (1992-07-01), Hollis et al.
patent: 5200186 (1993-04-01), Gabetta et al.
patent: 5474774 (1995-12-01), Walker et al.
patent: 5525341 (1996-06-01), Walker et al.
patent: 5646178 (1997-07-01), Walker et al.
patent: 5650432 (1997-07-01), Walker et al.
patent: 1054899 (1991-10-01), None
patent: 3027933 (1981-02-01), None
patent: 3427014 (1986-01-01), None
patent: WO 90/13304 (1990-11-01), None
patent: WO 92/06695 (1992-04-01), None
patent: WO 95/26197 (1995-10-01), None
patent: WO 96/30033 (1996-10-01), None
patent: WO 99/12541 (1999-03-01), None
CRC Handbook of Fruit Set and Development: pp. 114, 115 and 117.*
Marwan, et al.; “Microbial Inhibitors of Cranberries”;Journal Food Science; vol. 51, No 4; 1986; pp. 1009-1013.*
Sobota; “Inhibition of Bacterial Adherence by Cranberry Juice: Potential Use for the Treatment of Urinary Tract Infections”;The Journal of Urology; vol. 131; 1984; pp. 1013-1016.*
Letter to the Editor Concerning Antiadhesion in Cranberry and Blueberry—New England Journal to Medicine, vol. 339 (15), 1085-1986. Oct. 8, 1998.
Fuleki, et al.; “Quantitative Methods for Anthocyanins. 1. Extraction and Determination of Total Anthocyanin in Crnberries”;Journal of Food Science; Vol. 33; 1968; pp. 72-77.
Fuleki, et al.; “Quantitative Methods for Anthocyanin
Mickelsen Jennifer N.
Mickelsen, Jr. Richard A.
Walker Edward B.
JLB, Inc.
Pattern Patricia
TraskBritt
Weber Jon P.
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