Anti-proliferative preparations

Details Anti-proliferative preparations Anti-proliferative preparations

1999-11-29

2002-01-29

Tate, Christopher R. (Department: 1651)

Drug, bio-affecting and body treating compositions

Plant material or plant extract of undetermined constitution...

Containing or obtained from narcissus

C424S773000, C424S775000, C424S776000

Reexamination Certificate

active

06342254

ABSTRACT:

FIELD OF THE INVENTION
The present invention concerns extracts of cells or tissue or their supernatants which can inhibit proliferation of cells or tissue. The invention also provides compositions comprising such extracts as well as pharmaceutical, cosmetic and agricultural uses of the compositions and extracts.
BACKGROUND OF THE INVENTION
Dormancy is a phenomena which is found in representatives of the plant kingdom as well as the animal kingdom.
The germination of various grains and seeds comprising the necessary propagation organs is delayed under certain circumstances and yet the grains or seeds are capable of germinating after various periods of time. The period of time in which germination of such seeds may be delayed varies and depends both on intrinsic properties of the seed as well as on the nature and extremity of the environmental conditions. Seeds have been shown to be in dormancy for a few days, a year, several years and even for more than several centuries (as was discovered lately in the case of some nympheaceae and seeds of trees of the Leguminosae family (Shen-Miller, J., et al.,
American Journal of Botany
. 82:1367-1380, 1995)).
In some cases, the capability to develop dormancy lies in the embryo envelopes. In such a case, the separation of the envelopes from the embryo, result in its immediate germination.
In other cases, chemical growth inhibitors capable of preventing germination are present in the embryo itself and thus even a bare embryo may remain dormant (such as in the case of Rosaceae plants such as Kerria, Peach, etc.).
In plants, a state of dormancy may be found in the whole plant or in one or more of its parts. Dormant plants are plants which have two main metabolic states in their growth cycle. In their dormant state, the plants' metabolism is extremely low, and the plant growth process is significantly inhibited although differentiation of certain cells may occur. In their active state, the plants' metabolism rate is higher, the cells divide and differentiate and there is significant growth of various parts of the plant. In some cases, the whole plant enters the dormant state. Such is the case in Narcissus plants in which during the dormant state the only remaining viable part is the bulb which is in its dormant state. In other cases, some parts of the plants may be active while other parts may be in dormancy such as, for example, is the case of apple trees.
Substances capable of inhibiting germination have also been shown to be present in the juice of fleshy fruits or in other plant organs which produce juice. Examples are tomatoes, grapes, kiwi, watermelon and grapefruit wherein pips present in the fruit do not germinate although their surroundings are suitable for germination due to the water within the fruit.
Several plant-derived substances having an effect on cell proliferation have been reported. For example, European Patent Application No. 0381514 describes compositions comprising both naturally derived as well as synthetically prepared sphingolipids which have growth inhibitory activity on various kinds of cells. Another well known plant-derived substance having an anti-mitotic effect on various kinds of human cells is the substance colchicine (Samson, F. E.,
A. Rev. Pharmac. Toxic
16:143 (1976)). The Narcissus alkaloid, pretazettine, was shown to have a cytotoxic effect on Rausher virus-carrier cells as well as anti-leukemic activity in leukemic mice although the predominant activity of the substance was shown to be an antiviral activity (Furusawa, E. et al.,
Chemotherapy
, 26:36-45, (1980) and Furusawa, E. et al.,
Proc. Soc. Exp. Biol. Med
. 152:186-191, (1976)).
Utex europaezis
seed extracts were shown to comprise a non glycoprotein lectin capable of reversibly inhibiting growth of certain lymphocytes as well as to inhibit the growth of various reticulo endothelial tumor cell lines (Pirofsky, B., et aL,
Vox-Sano
, 42:295-303, (1982) and Pirofsky, B., et al.,
J. Biol. Response Mod
., 2:175-185, (1983)). Root extract of
Panex ginseng
was shown to decrease DNA synthesis measured by [H
3
]-thymidine incorporation of V 79 Chinese hampster lung cells. Another substance, Narciclasine obtained from bulbs of various Narcissus varieties was shown, amongst other of its activities, to inhibit growth of wheat kemal radicals (Ceriotti, G., et al,
Tumors
53:359-371 (1967)). Bulbs of
Pancratium littoral
collected in Hawaii were found to contain a product designated pancratistatin capable of inhibiting growth of various neoplastic cell lines in vitro (Pettit, G. R., et al.,
J. Nat. Prod
., 49:995-1002 (1986)).
Against this, many plant extracts having an opposite effect on cells, i.e., capable of augmenting their proliferation were also described such as, for example, the methanolic extract from the root of
Scutellaria baicalensis
georgi were shown to significantly augment the cellular activity of fibroblasts (Chung, C.P., et al,
Planta-Med
, 61:150-153, (1995)). Gibberellin-like growth substances were found in six different plant species having bulbs (Staby, G. L.,
Hort. Science
, 399-400 (1970)). Several cytokinins which were found in roots that developed from Narcissus bulbs had an effect on bulb growth of the plants in which they were detected (Vanstaden, J. V.,
Pflanzenphysiol
., 86:323-30 (1978)).
The phenomena of dormancy may also be found in the animal kingdom, for example, in the small crustacean Artemia salina (Finamore and Clegg Ln: The Cell Cycle, Academic Press Ed., 249-278, 1969). The natural environment of this marine crustacea is usually briny ponds. After fertilization, the early stages of development of artemia involve the formation of a blastula which then becomes a gastrula. Under severe environmental conditions such as dehydration (drought), the gastrula is capable of forming a cyst wherein the whole organism enters a dormancy phase. The dormant artemia gastrula (commonly miscalled “artemia eggs”) are capable of remaining in their dormant state for many years. When the encysted gastrula are rehydrated, the various metabolic activities of the artemia are resumed and protein synthesis can be seen after about 10 minutes. However, DNA synthesis and cell division are absent until about after 60 hours (Le Gal, Y, In: Biochinie Marine, (Ed. Masson) p. 176, 1988).
Various plant derived compositions (such as retinoic acid U.S. Pat. No. 5,438,073) and &agr;-hydroxy acids (Ditre, C. M., et al.,
J. Am. Acad Dermatol
., 34:187-195, 1996)) as well as animal derived extracts have been proposed for use in the cosmetic field for stimulating the proliferation and renewal of epidermal cells. Such compositions were considered to be useful in the cosmetic field where it is accepted that the natural renewal process of epidermis is slowed down with aging. It is believed that removal of the outer surface with simultaneous stimulation of growth of new cells in the inner layers of the epidermis to divide and migrate to the outer surface, will result in skin renewal and in a younger skin appearance. However, it is also known and has been recently shown that the increase in cell division is a crucial factor in converting normal cells into premalignant or malignant cells (Ames, B. N. et al,
Environ. Health Perspect
101:35-44 (1993)).
It is also believed today that normal human and animal cells have a finite capacity to replicate. It has been shown that the number of mitotic events that cultured normal animal cells can undergo appear to be inversely related to the age of the donor from which they were obtained (Hayflick, L.,
Clin. Geriatr. Med
., 1:15-27, (1985)). It has also been shown that cell cultures obtained from patients with accelerated aging syndromes undergo less replications than cell cultures obtained from age matched control individuals.
GLOSSARY
The following is the meaning of some terms of which will be used in the text below:
Dormancy—a state in which there is a marked decrease in the metabolic rate of cells or tissues resulting in the inhibition of growth and proliferation of the cells or tissue.
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