Drug – bio-affecting and body treating compositions – Extract – body fluid – or cellular material of undetermined... – Digestive system
Reexamination Certificate
2000-08-15
2002-06-04
Carr, Deborah D. (Department: 1621)
Drug, bio-affecting and body treating compositions
Extract, body fluid, or cellular material of undetermined...
Digestive system
C424S548000, C424S551000, C426S805000, C514S558000, C514S559000, C514S560000, 55, 55
Reexamination Certificate
active
06399105
ABSTRACT:
FIELD OF THE INVENTION
This patent relates to the general field of therapeutic products and methods to inhibit certain disease states related to the general medical field of human and veterinary pharmacology wherein the activation of the lipoxygenase pathways contribute to the pathological condition. Agents which inhibit or modulate the 5-lipoxygenase or 12-lipoxygenase pathways are known to be useful in the medical arts. Agents with little or no toxicity that inhibit systemic or dermatological inflammations are useful in the healing arts. This patent also relates to the field of pigmented agents useful in the aquaculture industry, wherein pigmented ingredients must be incorporated into aquatic feeds in order to bring about a deposition of color either in the flesh of the animal, or on the skin or shell thereof.
More particularly, the present invention concerns certain novel lipids derived from the class Holothuridea, or sea cucumber, and especially, the
Cucumaria frondosa
variety found in Maine and the North Atlantic. Any species of sea cucumber parts will suffice for raw material from which to extract the compounds of the present invention. The oils of such sea cucumbers from any species can be used for pigmentation of aquatic species by incorporation into feeds, as well as for the treatment or amelioration of diseases in which products of lipoxygenase enzyme activity or the reaction of leukotrienes contribute to the pathological condition. That is, the novel lipids derived from any class or species of sea cucumber inhibit lipoxygenase enzymes and/or bind leukotriene receptors. Lipoxygenase enzymes are well known in the arachidonic acid cascade. These oils, designated RED OIL and GOLD OIL, can be used as-is for immunosuppressive purposes and also provide raw materials from which to derive ingredients of immunosuppressive drugs suitable to ameliorate immune responses due to organ transplant or autoimmune response in diseases such as lupus or rheumatoid arthritis. These oils or derivatives thereof from molecular distillation are suitable ‘as-is’ or may be further fractionated by means known to the arts and can be used to reduce, suppress, inhibit, or prevent unwanted immune responses, e.g., in humans or animals requiring immunosuppression. Examples of such situations include. but are not limited to, treatment or prevention of autoimmune diseases such as diabetes, lupus, and rheumatoid arthritis. Immunosuppression is also frequently needed in conjunction with organ transplants. Immunosuppressive agents can also be utilized when a human or animal has been, or may be, exposed to superantigens or other factors known to cause overstimulation of the immune system. The compounds of the subject invention are also useful as standards to assess the activity of other putative immunosuppressive agents. The subject invention further pertains to pharmaceutical compositions containing these compounds. These oils are also shown by the present invention to inhibit angiogenesis, as shown in the chick chorioallantoic membrane assay (Knighton et al., 1977). The pigmented oil, designated for purposes of this patent as RED OIL. has been shown to contain surprising amounts of the carotenoids, canthaxanthin and astaxanthin, and is suitable for adding to commercial fish feeds in order to bring color deposition to the flesh or skin of particular species in need of same.
BACKGROUND
The present invention relates to novel compounds, pharmaceutical compositions and methods of use for the treatment of diseases in which the 5- and 12-lipoxygenase activity contributes to the pathological condition. The present invention also relates to products derived from the lipid fractions of sea cucumber tissue which ameliorate immune responses and which can also be incorporated into aquatic diets for the purpose of imparting color to the flesh or skin of such fish or shrimp. Although there have been reports in the literature concerning marine lipids from certain fish in the treatment of various arthritis related diseases, sea cucumber lipids have never been included in any studies, nor is there any evidence that the inflammation inhibitory mechanisms known of vertebrate fishes in mammalian systems is relevant to this invention (DeLuca et al., 1995). It is also known that certain marine sponges and ascidians possess immunomodulatory or immunosuppressive activities, but there are no reports in the field of marine pharmacology that sea cucumber lipids have been discovered to possess any such inhibitory activities useful in the medical arts (Konig and Wright, 1995).
More particularly, the compounds defined below inhibit the 5-lipoxygenase pathway and the 12-lipoxygenase pathway in mammals. Lipoxygenase pathway products such as the leukotrienes B
4
, C
4
, D
4
and E
4
, 5-hydroxyeicosatetraenoic acid, 5-hydroperoxyeicosatetraenoic acid and 12-hydroxyeicosatetracnoic acid are related to the above described conditions. Specific conditions for use of the present novel lipoxygenase-inhibiting compounds, pharmaceutical compositions thereof and the novel method of use in accordance with the present invention include allergy; asthma; arthritis; skin disorders including psoriasis, a topic dermatitis and acne; inflammation-including inflammatory bowel diseases or pain; various cancers including prostate, lung, colorectal, and skin; and cardiovascular disorders including myocardial ischemia and infarction, angina, arrhythmias, stroke, migraine and atherosclerosis.
The compounds of the present invention are derived from the lipid fractions of sea cucumber of any species or sub-phyla; from the de-pigmented fraction of such lipid fraction; from the molecular distillation phases as are known to those skilled in the arts; or from the chromatographic column separations of same; from the epidermal. dermal, anterior, posterior, or intestinal mass including respiratory trees, gonads, cuverian tubules or polian vesicles of any sea cucumber.
Sea cucumbers of various species provide medically active fractions useful to die healing arts. U.S. Pat. No. 5.519,010 teaches that a de-polymerized polysaccharide is useful as an anti-coagulant. U.S. Pat. No. 5,770,205 by Collin teaches that sea cucumber tissues extracted by various methods possess anti-inflammatory activity useful in the human and veterinary medical arts. Glycosides from sea cucumber organs have been shown to contain anti-cancer agents (Miyamoto et al., 1990). None of the above describe a lipid from sea cucumber which inhibits any lipoxygenase pathway, nor inflammation, nor describes any utility of such sea cucumber-derived agents to inhibit pathological disease conditions in which lipoxygenase products, isomers, or metabolites contribute to such condition. Nor do any of the above patents present any art wherein such lipids provide an immunomodulatory activity in a mammal.
The present invention teaches that both the pigment-rich lipid materials and the de-pigmented lipid materials and the Light Phases recovered from molecular distillation of any of the pigmented or de-pigmented sea cucumber lipid materials are able to inhibit the 5-lipoxygenase enzyme activity in human neutrophils and the 12-lipoxygenase enzyme in human platelets.
There are currently many patents describing agents which purport to inhibit the leukotriene and 5-lipoxygenase and 12-lipoxygenase pathways in mammals. Some of these compounds are effective, and some have toxic side-effects or cannot be cost-effectively produced. It is an object of the present invention that the production of sea cucumber oils and their derivatives which can be incorporated into ointments, suppositories, and embodied into orally administered or injected medicines or into medicine administered by other means, provides a cost effective and readily available means to modulate the leukotriene pathway in mammals and thus will contribute to the therapeutic treatment of such diseases as cancer, psoriasis, atopic dermatitis, etc. in which leukotrienes, LTB
4
, 5-HETE and 12-HETE contribute to the pathological condition.
OBJECTS OF THE PRESENT INVENT
Carr Deborah D.
Rothwell Figg Ernst & Manbeck
LandOfFree
Sea cucumber carotenoid lipid fraction products and methods... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Sea cucumber carotenoid lipid fraction products and methods..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Sea cucumber carotenoid lipid fraction products and methods... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2981338