Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
1998-05-08
2002-09-10
Shippen, Michael L. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C514S720000
Reexamination Certificate
active
06448450
ABSTRACT:
FIELD OF THE INVENTION
The field of the invention is a diphenylethylene derivative and its use for treatment of diabetes.
BACKGROUND OF THE INVENTION
Extracts of the leaves, flowers, and gum of the tree
Pterocarpus marsupium
Roxb. (Leguminosae), also known as the Indian Kino Tree, have been used traditionally for the treatment of diarrhea, toothaches, fever and urinary and skin infections. Extracts of the bark have been long regarded as useful for the therapy of diabetes. Hypoglycemic activity of a naturally occurring pterostilbene, 3,5-dimethoxy-4′-hydroxy-trans-stilbene, isolated from the heartwood of pterocarpus marsupium as been reported by Manickam et al.,
J. Nat. Prod.,
1997, 60:609-610. However, this pterostilbene is water insoluble and has not been shown to be efficacious in the treatment of diabetes, particularly in instances where insulin is present but inactive. The cause of diabetes is yet unknown, although both genetics and environment appear to be factors. Insulin dependent (Type I) and non-insulin dependent (Type II) are the types of diabetes. Type I is an autonomic immune disease in which the responsible autoantigen is still unknown. Patients of Type I need to take insulin intravenously to survive. However, Type II diabetes, the more common form of the disease, is a metabolic disorder resulting from the body's inability to make a sufficient amount of insulin or to properly use the insulin that is produced within the body. Insulin secretion and insulin resistance are considered the major defects, however, the precise genetic factors involved in the mechanism remain unknown.
Patients with diabetes usually have one or more of the following defects: less production of insulin by the pancreas; over secretion of glucose by the liver; impairment of glucose uptake by the skeletal muscle; defects in glucose transporters; desensitation of insulin receptors; and defects in the metabolic breakdown of polysaccharides. Other than the intravenous application of insulin, there are four classes of oral hypoglycemic agents in use.
Approved
Mechanisms of
Class
Drugs
Action
Limitations
sulfur urea
4 (1st
acts on
dev. of
generation)
pancreas to
resistance
and
release more
2 (2nd
insulin
generation)
biguanides
metformin
reduces
liver
glucose
problems,
secretion by
lactic
liver;
acidosis
improves
insulin
sensitivity
alpha-
acarbose
interferes
only useful
glucosidase
with
at post-
inhibitor
digestive
pradiandio
process;
level
reduces
glucose
absorption
thiazolidine
troglipzone
reduces
“add-on”
-dione
insulin
with
resistancy
insulin; not
useful for
people with
heart and
liver
disease
As is apparent from the above table, each of the current agents available for use and treatment of diabetes has certain disadvantages. Accordingly, there is a continuing interest in the identification and development of new agents, particularly, water soluble agents which can be orally administered, for the use of treatment of diabetes.
Besides the pterostilbene discussed above, (−)-epicatechin, has also been isolated from pterocarpus marsupium by Sheehan et al.,
J. Nat. Prod.,
1983, 46:232, and has been reported as having a hypoglycemic effect. See also Chakravarthy et al.,
Life Sciences,
1981, 29:2043-2047. Other phenolic type compounds have been isolated from pterocarpus marsupium by Maurya et al.,
J. Nat. Prod.,
1984, 47:179-181; Jahromi et al.,
J. Nat. Prod.,
1993, 56:989-994; and Maurya et al.,
Heterocycles,
1982, 19:2103-2107.
SUMMARY OF THE INVENTION
A diphenylethylene is provided having the following formula I.
Pharmaceutical compositions containing the compound of the formula I are provided for treatment of diabetes comprising of therapeutically effective amount of the compound in a physiologically acceptable carrier.
A method of treating diabetes is also provided comprising the step of orally administering to a subject suffering from a diabetic condition a therapeutically effective amount of a compound of formula I.
REFERENCES:
patent: 2496968 (1950-02-01), Walton
patent: 4996237 (1991-02-01), Pettit
patent: 5430062 (1995-07-01), Cushman
patent: 5547983 (1996-08-01), Charpentier
patent: 5569786 (1996-10-01), Pettit
patent: 5886029 (1999-03-01), Dhaliwal
Chakravarthy et al., “The Prophylactic Action of (-)-Epicatechin Against Alloxan Induced Diabetes in Rats,”Life Science,vol.29, pp. 2043-2047, 1981.
Farbooniay et al., “Antihyperlipidemic Effect of Flavonoids from Pterocarpus Marsupium,”Journal of Natural Products,vol. 56, No. 7, pp. 989-994, Jul. 1993.
Manickam et al., “Antihyperglycemic Activity of Phenolics fromPterocarpus marsupium,”Journal of Natural Products,vol. 60, No. 6, pp. 609-610.
Maurya et al., “Marsupsin, A New Benzofuranone from Pterocarpus Marsupium Roxb.,”Heterocycles,vol. 19, No. 11, pp. 2103-2107, 1982.
Maurya et al., “Constituents of Pterocarpus Marsupium,”Journal of Natural Products,vol. 47, No. 1, pp. 179-181, Apr. 1983.
Sheehan et al., “A Constituent of Pterocarpus Marsupium, (-)-Epicatechin, As a Potential Antidiabetic Agent,”Journal of Natural Products,vol. 46, No. 2, pp. 232-234, 1983.
Chansouria Jai P.
Medicherla Satyanarayana
Nag Bishwajit
Ray Anil B.
Calyx Therapeutics Inc.
Pillsbury & Winthrop LLP
Shippen Michael L.
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