WO2010096925A1 - Homotaurine-supplemented and/or enriched edible material, methods of preparation an d uses - Google Patents

Abstract

The invention relates to methods, materials and compositions for administering homotaurine in a subject, preferably a human subject. The invention encompasses compositions and materials enriched/supplemented in homotaurine. Preferred compositions include nutraceutical, and food compositions for use in neuroprotection and for improving or preserving cognitive and/or memory function, as well as for the prevention and treatment of a disease or condition wherein amyloid-β amyloidogenic peptides or proteins are present.

Description

HOMOTAU RINE-SUPPLEMENTED AND/OR ENRICH ED EDIBLE MATERIAL, METHODS OF PREPARATION AND USES Field of the Invention

The invention relates to methods and compositions for delivering 3-amιno-1- propanesulfonic acid (homotaunne) in a subject, preferably a human subject The invention encompasses edible materials with homotaunne content higher than natural occurrence Preferred materials include homotauπne-supplemented and/or enriched plant, algal, fungal or animal compositions, for use in the preparation of compositions such as nutraceuticals, dietary supplements or food additives or ingredients The materials and compositions are also useful as nutraceuticals for maintaining brain cells health, for neuroprotection, for improving or preserving cognitive, memory and brain function, or for preventing or treating a disease or condition involving beta-amyloid deposition or neuronal cell toxicity

Background of the Invention

Homotaunne (3-amιno-1-propanesulfonιc acid) occurs naturally in various edible seaweeds and is known to be useful for protecting the brain structure associated with memory and learning, protecting memory function, sustaining brain cell health, maintaining verbal skills and comprehension ability, as well as supporting planning and execution skills

Homotaunne is naturally found in species of edible seaweed However, homotaunne content in seaweeds is low and variable, making it difficult to control the amounts of homotaunne ingested to obtain the optimal health benefit

It is desirable to obtain a composition with improved ease of administration, providing additional nutrients, such as vitamins, minerals, fibers, proteins, and/or polyunsaturated fats (e g DHA or EPA), and/or lessening gastrointestinal side effects

Summary of the Invention

The invention includes methods and compositions for delivering in a subject preferably a human subject, homotaunne, or acceptable salts thereof Homotaunne (3- amιno-1-propanesulfonιc acid) has the following structure

HOMOTAURINE

According to one aspect, the present invention relates to edible materials and compositions enriched or supplemented with hoimotauπne, i e containing a concentration of homotauπne higher than naturally occurring In one embodiment, the material before homotaurine enrichment or supplementation contains less than 10%, less than 5%, less than 2%, less than 1 %, less than O 5%, less than O 2%, less than O 1 %, less than O 01 %, less than 0 001% of homotaurine by weight of dried material In one embodiment the material before homotaurine enrichment or supplementation contains traces, negligible amounts, or no homotaurine or undetectable amounts of homotaurine by weight of dried material In one embodiment, the edible material to be enriched or supplemented (the absorbent material) in homotaurine is selected from plants, algae, fungi and animals, preferably plants or algae, preferably algae, most preferably brown green or red algae

In one aspect of the invention the edible material comprises a red seaweed of a genera selected from the group consisting of Chondrus, Eucheutna, Gigartina, Gracilaπa, Hypnea, Lithothamnion, Meristotheca Palmaria, Grateloupia, Rhodymenia, Acrosorium and Porphyra, preferably a red seaweed of a species selected from the group consisting of Porphyra (Nori or Laver), Grateloupia livida, Chondrus ocellatus Rhodymenia intricata, Rhodymenia palmata, and Acrosorium uncinatum In another aspect of the invention, the edible material comprises a brown seaweed of a genera selected from the group consisting of Alaria, Ascophyllum, Durvillaea, Eisenia, Fucus, Himanthalia, Hizikia, Laminaria, Macrocystis, Sargassum and Undana In another aspect of the invention, the edible material comprises a green seaweed of a genera selected from the group consisting of Caulerpa, Codium, Enteromorpha, Monostroma Cladophora and Ulva , preferably a seaweed of the species Cladophora densa In another aspect of the invention, the edible material comprises a seaweed of a genera selected from the group consisting of Spirulina and Chlorella

The present invention also relates to the process of supplementing and/or enriching edible absorbent material with homotaurine, said process comprising the step of absorbing a solution of homotaurine in at least one absorbent material, and optionally filtering and/or drying and/or powdering the enriched or supplemented material obtained In one embodiment, the edible absorbent material is derived from plants, algae, fungi or animals, or a mixture thereof In another embodiment the edible absorbent material comprises edible plants or algae, preferably algae, most preferably edible green brown or red algae In another embodiment, the supplemented and/or enriched edible material comprises about 0.2% to about 60%, about 0 5% to about 50%, about 1% to about 40%, about 1% to about 20%, about 1% to about 10%, about 10% to about 40%, about 10% to about 30%, or about 20% to about 40% of homotauhne by weight The present invention further relates to the process of: preparing homotauπne- enriched and/or supplemented seaweed materials comprising the step of absorbing homotaurine in or on the seaweed In one embodiment, the process comprises the steps of: providing dried seaweed, hydrating the dried seaweed in a solution containing homotaurine, preferably an aqueous solution, separating the seaweed from the solution, drying the enriched/supplemented seaweed and optionally grinding or powdering the enriched/supplemented seaweed material

In one aspect, the homotaurine-enriched and/or supplemented edible material is in a form suitable for direct consumption or administration. In another aspect, the homotauπne- enriched and/or supplemented edible material is in a powder form suitable for direct consumption or administration or for direct use as a condiment or food additive In another aspect, the homotaurine-enriched and/or supplemented edible material is in a form suitable for use in the preparation of compositions such as nutraceuticals, food additives or food preparations (foodstuffs) in combination with other ingredients or carriers. In yet another aspect, the homotaurine-enriched and/or supplemented edible material is in a powder form suitable for use in the preparation of compositions such as nutraceuticals, food additives or food preparations (foodstuffs) in combination with other ingredients or carriers.

In a further aspect, the invention includes compositions, such as nutraceutical compositions, food additives and foodstuffs, comprising a homotaurine-supplemented or enriched edible material in combination with an acceptable carrier. In one aspect, the composition is in a suitable form for direct oral administration, such as caplets, pills, and the like, or in a powder form to be added to food, drinks, and the like

Accordingly, the present invention equally encompasses the enriched/supplemented materials, as well as nutraceutical compositions and food additives and foodstuffs containing them, as well as methods for employing them in neuroprotection, improving or preserving cognitive and memory function.

In one aspect, the materials and compositions of the invention are useful for protecting memory function. In another aspect, the materials and compositions of the invention are useful for protecting the brain structure associated with memory and learning, for preserving memory, for sustaining brain cell health, for maintaining verbal skills and comprehension ability and to support planning and execution skills. The invention also relates to a method for providing neuroprotection to a subject comprising administering to the subject a nutraceutically effective amount of a composition or material of the invention, such that neuroprotection is provided to the subject. The invention further relates to a composition of the invention for use in the treatment or prevention of inflammation in the brain, neuronal cell toxicity, neuronal cell death or neuronal cell loss in a subject having a condition or disease in which Aβ amyloidogenic proteins or peptides are present, or being susceptible or predisposed to said condition or disease, including a disease or condition characterized by Aβ deposition, as well as in the treatment or prevention of diseases and conditions such as Alzheimer's disease, cerebral amyloid angiopathy, Down's syndrome, mild cognitive impairment, mild-to-moderate cognitive impairment, aging of the brain, age-associated cognitive impairment, and age-associated memory impairment

The invention also relates to a method for reducing side effects of homotaurine in a human subject (e.g., reducing or preventing gastrointestinal intolerance), which occurs when homotaurine is administered in an immediate release formulation to a human subject, wherein homotaurine is administered in the form of an homotaurine-enriched and/or supplemented edible material or composition comprising same, which yields or generates homotaurine after being administered to or consumed by said human subject.

In one aspect, the material or composition comprising the material releases homotaurine preferentially or at a higher rate in a less acidic environment Preferably, homotaurine is released preferentially or at a higher rate at a pH above about 4, preferably at a pH above about 5, preferably at a pH above about 6. Preferably, homotaurine is released from the material or composition comprising the material preferentially or at a higher rate at a pH of about 6.9 as compared to a pH of about 2.0 The invention also relates to a method of treating or preventing a disease or condition as detailed in the present application, wherein the bioavailability of homotaurine, AUC of homotaurine, brain levels of homotaurine, CSF levels of homotaurine, C_max of homotaurine, T_max of homotaurine, and/or bio-absorption of homotaurine is increased. In one embodiment, the level of homotaurine in the brain of said human subject is increased Additional objects, advantages and features of the present invention will become more apparent upon reading of the following non-restrictive description of preferred embodiments which are exemplary and should not be interpreted as limiting the scope of the invention Detailed Description of the Invention

/ Definitions

All technical and scientific terms used herein have the same meaning as commonly understood by one ordinary skilled in the art to which the invention pertains. For convenience, the meaning of certain terms and phrases used herein are provided below

To the extent the definitions of terms in the publications, patents, and patent applications incorporated herein by reference are contrary to the definitions set forth in this specification, the definitions in this specification control The section headings used herein are for organizational purposes only, and are not to be construed as limiting the subject matter disclosed.

It should be noted that, the singular forms "a", "an", and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to a composition containing "a carrier" includes a mixture of two or more carriers. It should also be noted that the term "or" is generally employed in its sense including "and/or" unless the content clearly dictates otherwise

The chemical structures herein are drawn according to the conventional standards known in the art. Thus, where an atom, such as a carbon atom, as drawn appears to have an unsatisfied valency, then that valency is assumed to be satisfied by a hydrogen atom even though that hydrogen atom is not necessarily explicitly drawn. Hydrogen atoms should be inferred to be part of the compound

As used herein, the terms "compound" and "homotaurine" and equivalent expressions refers to 3-amino-1-propanesulfonιc acid, its zwitterionic form (inner salt), and acceptable salts and solvates thereof The compound may be of natural source (extracted or purified from a natural source, e.g. a seaweed) or may be synthetic (e.g. prepared synthetically on site or provided by a commercial source). The term further includes natural extracts containing at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% of homotaurine in the dried extract. In general, the compound may be hydrated or solvated. The compound may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated herein and are intended to be within the scope of the present invention

A "nutraceutically acceptable salt", "acceptable salt" or "suitable salt" of a compound means a salt of a compound that is acceptable for human consumption. Desirable salts of a compound, for example, will retain or improve the biological and/or chemical and/or physical properties of the free acid of homotaurine as defined herein, and will not be biologically or otherwise undesirable Examples of acceptable salts are also described, for example, in Berge et al. , J Pharm Sci. 66, 1-19 (1977). Salts include base addition salts formed by the replacement of the acidic proton of the sulfonic acid of homotauπne by, for example, a metal ion, including, an alkali metal ion {e g. lithium, sodium, potassium), an alkaline earth ion {e.g. magnesium, calcium, barium), or other metal ions such as aluminum, zinc, iron and the like; or by an organic base such as ammonia, ethylamine, diethylamme, ethylenediamine, Λ/,Λ/'-dιbenzylethylenediamine, ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine, piperazine, chloroprocain, procain, quaternary ammoniums (e.g. L-carnitine, L-carnitine alkanoyl derivatives such as acetyl, propionyl and butyryl-L-carnitine, choline, choline derivatives such as acetylcholine, butyrylcholine, propionylcholine, other aliphatic esters of choline, fatty acid esters of choline such as eicosapentaenoyl (EPA), docosahexaenoyl (DHA), docosapentaenoyl (DPA), capryloyl, lauroyl, myristoyl, palmytoyl, stearoyl, oleoyl, ricinoleoyl, linoleoyl, alpha-linolenoyl, and arachidonoyl, phosphorylcholine, phosphatidylcholines, trimethylglycine, and the like), ammo acids (e.g. L-arginine, L-lysine, histidine, and the like), amine-containing or polyamine compounds (e.g putrescine, spermidine, spermine, galanthamine, dimethylaminoethanol, and the like), vitamins having a basic group (e.g. vitamins B1 (thiamine), B2 (riboflavin), B3 (niacin or nicotinic acid), B4 (adenine), B6 (pyridoxine), B12 (cobalamine), vitamin U (S-methylmethionine) or folic acid), alkaloids (e.g. huperzine A and tetrandnne), and the like

Acceptable salts may be prepared from the parent agent by conventional chemical methods. Generally, such salts are prepared by reacting the free base forms of the counterion with a stoichiometric amount of the acid form of homotaurine (or its zwitterion) in water or in an organic solvent, or in a mixture of the two. Salts may be prepared in situ, during the final isolation or purification of the agent or by separately reacting homotaurine in its free acid or zwitterion form with the desired corresponding base, and isolating the salt thus formed

All acid, salt, base, and other ionic and non-ionic forms of the compound are included in the described materials, compositions, preparations, methods and uses of the invention. For example, if homotaurine is shown as an acid herein, its salt and zwitterionic forms are also included Likewise, if homotaurine is shown as a salt, the acid and/or zwitterionic forms are also included

As used herein, the terms "enriched/supplemented", "enriched or supplemented", or "enriched and/or supplemented" and equivalent expressions refers to a material or composition comprising such material in which the content in homotaurine is higher than naturally occurring in the material. Prior to enrichment/supplementation, the material's content in homotaurine may be isolable, measurable, negligible, or undetectable, or the material may contain no homotaurine

"Abeta", "AB", or "β-amyloid", is defined as any peptide resulting from beta- secretase mediated cleavage of Beta Amyloid Precursor Protein (APP), including for examples peptides of 37, 38, 39, 40, 41 , 42, and 43 amino acids, and extending from the beta-secretase cleavage site to amino acids 37, 38, 39, 40, 41 , 42, or 43 It also includes N- terminal truncated species of above peptides, such as the pyroglutamic forms pE3-40, pE3- 42, pE3-43, pE1 1-42, pE1 1-43 and the like For convenience of nomenclature, "AB_1-42", may be referred to herein as "AB(1-42)" or simply as "AB₄₂" (and likewise for any other amyloid peptides discussed herein) As used herein, the terms "Abeta", "AB', "B-amyloid", "amyloid-B" are synonymous referring collectively to truncated and non-truncated peptide species of the sequence between β- and γ-cleavage sites of APP

The term "amyloid-β disease, disorder or condition" or "amyloid-β related disease, disorder or condition" may be used to designate any one of vascular dementia, early Alzheimer's disease, Alzheimer's disease (AD), including sporadic (non-hereditary) and familial (hereditary) forms, age-related cognitive decline, cerebral amyloid angiopathy (CAA), hereditary cerebral hemorrhage, senile dementia, Down's syndrome (DS), inclusion body myositis (IBM), age-related macular degeneration (ARMD), mιld-to-moderate cognitive impairment, mild cognitive impairment (MCI), and conditions associated with aging such age-associated memory impairment (AAMI)

As used herein the term "effective amount" or "nutraceutically effective amount" refers to the amount of enriched/supplemented material or composition or its content in homotaurine, upon single or multiple administration to or consumption by the subject, which provides the desired effect to the subject An effective amount can be readily determined by the use of known techniques and/or by observing results obtained under analogous circumstances In determining the effective amount administered, a number of factors are considered, including, but not limited to the size, age, and general health of the subject, the specific disease or condition involved, the degree, involvement, or severity of the disease or condition the response of the individual subject, the mode of administration, the bioavailability characteristics of the preparation administered, the use of concomitant medication, and other relevant circumstances The effective amount refers to an amount of the material, composition or food preparation or its content in homotaurine to obtain significant benefit to the subject, either by providing neuroprotection, protecting memory function, protecting the brain structure associated with memory and learning, by preserving memory, by sustaining brain cell health, by maintaining verbal skills and comprehension ability and/or by supporting planning and execution skills The term "lessening metabolism of homota urine (or related terms such as reduction, less, lowering, reducing, lowered, etc) refers to decreasing the degree or amount of first-pass metabolism in the Gl tract or liver of homotaurine by e.g., 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or even 100%, which decrease is with respect to the degree or amount of metabolism of homotaurine that occurs when the same equivalent molar dose of homotaurine is administered orally in water solution Preferably such % decreases are achieved also with respect to homotaurine administered orally in the formulation of Table 3 of US published application 2006/0079578, filed on April 12, 2005, which reference is incorporated by reference in its entirety for all purposes The term "reduction of side effects of homotaurine" refers to decreasing the amount of or severity of one or more side effects of homotaurine by, e.g., 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 99.9%, or even 100%, which decrease is with respect to the amount of or severity of a side effect of homotaurine that is exhibited when the same equivalent molar dose of homotaurine is administered orally in water solution or in an immediate release solid formulation (e g. lose-filled capsules) Examples of side effects include, without limitation, gastro-mtestinal intolerance, upset stomach, nausea, dizziness and vomiting. Preferably such % decreases are achieved also with respect to homotaurine administered orally in the formulations of Table 3 of US published application 2006/0079578, filed on April 12, 2005 More generally, the terms lessening etc., increasing etc., refer in context herein to the percentage changes, e.g., by 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 125%, etc., or even more, e.g., 2, or 4 fold, or even more

"Nutraceutically acceptable" or simply "acceptable" associated with a term such as salts, inert ingredients, carriers, excipients, additives, ingredients, etc., refers to salts, inert ingredients, carriers, excipients, additives, ingredients, etc , suitable for use in contact with the tissues of humans and animals without undue toxicity, incompatibility, instability, irritation, and the like, commensurate with a reasonable benefit/risk ratio. In general, the term includes what is commonly used and generally accepted as safe by the nutraceutical and the food industry. It preferably refers to salts, inert ingredients, carriers, excipients, additives, ingredients, etc , approved or approvable by a regulatory agency of the Federal or state government or listed in the U S Pharmacopoeia or other generally recognized pharmacopoeia or Food administration or have been generally used as a dietary or food ingredient in animals and more particularly in humans

"Acceptable vehicle" or "nutraceutically acceptable vehicle" and equivalent expressions refer to a diluent, adjuvant, excipient, or carrier with which a material is administered In general, the term "composition" and equivalent expressions refer to an enriched/supplemented edible material of the invention in a form ready for consumption or administration The term composition equally includes, for example, nutraceutical compositions, food additives and food preparations (foodstuffs). The terms "nutraceutical", "nutraceutical composition", "dietary supplement" or "dietary composition", "food supplement", "nutritional composition" or "nutritional supplement" and equivalent expressions refer to an enriched/supplemented edible material of the invention, optionally in combination with at least one nutraceutically acceptable vehicle, in a form suitable for administration of the material and compound therein to a subject, e.g. tablets, capsules, etc. The term "food additive" refers to an enriched/supplemented edible material of the invention in a form ready to be used in the preparation of foodstuffs, such as powders to be added in the process of making foods, or as a ready-to-use powder form to be added to prepared food, such as spices, condiments, herbs, herbal salt, etc. The terms "foodstuff¹, "food compositions" or "food preparations" refers to an enriched/supplemented edible material of the invention in a form that can be consumed, for example, eaten, drank, or ingested by a subject

"Preventing" or "prevention" refer at least to the reduction of likelihood of the risk of (or susceptibility to) acquiring a disease, disorder or condition (ι e., causing at least one of the clinical symptoms of the disease, disorder or condition not to develop, or slow down or delay onset, in a subject that may be exposed to or predisposed to the disease but does not yet experience or display symptoms of the disease).

"Treating" or "treatment" of any disease, disorder or condition refer, in some embodiments, to ameliorating the disease, disorder or condition (i.e., arresting or reducing the development of the disease or at least one of the clinical symptoms thereof). In certain embodiments "treating" or "treatment" refers to ameliorating at least one physical parameter, which may or may not be discernible by the subject. In certain embodiments, "treating" or "treatment" refers to inhibiting the disease, disorder or condition, either physically (e g , stabilization of a discernible symptom), physiologically (e g., stabilization of a physical parameter), or both. In certain embodiments, "treating" or "treatment" refers to delaying the onset of the disease, disorder or condition. The term "treating" refers to any indicia of success in the treatment or amelioration of an injury, pathology or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the subject; slowing in the rate of degeneration or decline, making the final point of degeneration less debilitating; improving a subject's physical or mental well-being; improving and/or preserving memory and cognitive functions; maintaining verbal skills and comprehension ability; maintaining or improving planning and execution skills; restoring and/or improving mental alertness and the ability to concentrate or, in some situations, preventing the onset of dementia. The treatment or amelioration of symptoms can be based on objective or subjective parameters; including the results of a physical examination, a psychiatric evaluation, or a cognition test such as CDR, MMSE, DAD, ADAS-Cog, or a subscale thereof (e.g. a subset of tests related to the memory aspect), or another test known in the art

Reference will now be made in detail to certain embodiments of materials, compositions and methods. The disclosed embodiments are not intended to be limiting of the invention

// Homotaurine-enήched and/or supplemented edible materials

The present invention relates to methods, materials, compositions and preparations for delivering in a subject, preferably a human subject, homotaurine, or salts thereof. The invention encompasses materials and compositions that will yield or generate homotaurine, either in vitro or in vivo. The present invention provides an edible composition comprising homotaurine at a concentration higher than naturally occurring. The edible composition comprises homotaurine absorbed onto an edible absorbent material. The absorbent material may be of a source selected from plants, algae, fungi and animals. Homotaurine is absorbed on the edible material either by hydrating the material with a homotauπne-contaimng solution or by mixing the material, dry or fresh, with homotauπne-containing powder and processing the resulting mixture such that homotaurine is absorbed on or in the edible material.

a) Edible absorbent material

The edible absorbent material to be used in the enrichment/supplementation comprises at least one edible material selected from plant, fungal, animals or algal material and/or mixtures thereof The edible absorbent material can be in any form, for example fresh, dried, chopped, powdered, and the like.

Examples of plant material suitable as absorbent material comprises, without limitation, grains and their bran, tuberous roots and other vegetables, fine herbs and spices, bean curds, tea leaves, and fruit materials. Examples of grains include, without limitation, rice, wheat, barley, rye, adlay, buckwheat, oat, millet, corn and the like, as well as bran from those grains. Examples of tuberous roots and other vegetables include, without limitation, potatoes, sweet potatoes, aroid, carrots, parsnips, beets, turnips, cauliflower, broccoli, cabbage, lettuce, and the like. Examples of tea leaves include, without limitation, fermented tea leaves (e g. black tea), half-fermented tea leaves (e.g Oolong tea), post-fermented tea leaves (e.g Pu-her tea), or unfermented tea leaves (e.g. green or white tea). Fruit materials include dried, stewed or fresh fruits as well as fruit peel or skin Examples of fruits include, without limitation, apples, pears, berries, grapes, citrus fruits, cherries, cranberries and the like Examples of dried fruits include, without limitation, raisins, craisins, apples berries, pineapples, bananas, and the like Nutrients content as well as beneficial properties associated with edible plants have long been established so it is not necessary to list them here

Examples of fungal material include edible mushrooms, for example whites (buttons or champignons de Paris), portabello and crimini (or baby portabello, portabellini), shiitake, maitake, hen-of-the-woods, oyster, enoki, and the like Such edible mushrooms may be dried or fresh Most species of mushrooms are high in fiber vitamins, such as vitamins of the B-group (niacin, thiamine and riboflavin), biotin, cobalamins, vitamin C and minerals such as iron selenium, potassium, and phosphorus

Non-limiting examples of animal absorbent material include fresh, dried, baked, cooked, or smoked meat products of cattle, ovine, porcine avian, fish or seafood origin Algal materials have long been used for healthcare and as dietary supplements especially in Asia Most seaweed species contain polyphenols, particularly phlorotannins which are free radical scavengers They also display a wide spectrum of carotenoids which have antioxidant properties When taken orally, seaweed are said to help compensate the body s deficiencies, stimulate general metabolism, strengthen natural defenses and boost energy Seaweeds are consumed as food in various forms raw as salad and vegetable, pickle with sauce or with vinegar relish or sweetened jellies and cooked for example, in soups Traditionally, seaweed has been used for traditional cosmetics and in herbal medicine for the treatment of cough, asthma hemorrhoid, boils, goitres stomach ailments, urinary diseases, and are believed to reduce the incidence of tumors, ulcers and headaches In addition to antioxidants seaweeds are a source of proteins and amino acids, carbohydrates, dietary fibers fatty acids (e g DHA, EPA) vitamins (e g , C, B1 , B2 B3 B6 and folic acid) pigments, macro and micro-elements (e g I, Ca Mg, K, Mn, P and Zn)

Examples of algae include brown, red and green algae Examples of genera of edible brown algae (pheophyceaes) include, without limitation, Alaria, Ascophyllum, Durvillaea, Eisenia, Fucus Himanthalia Hizikia, Lammaria (or Kelp or Saccharina japonica),

Macrocystis Sargassum and Undaria (e g undaria pinnatifida) Examples of genera of edible green algae (chlorophyceaes) include without limitation, Caulerpa, Codium Enteromorpha, Monostroma Cladophora (e g Cladophora densa) and Ulva Other algae also include species of the genera Spirulina and Chlorella (e g Chlorella vulgaris) Examples of genera of edible red algae (rhodophyceaes) include, without limitation Chondrus, Eucheuma, Gigartina, Gracilaria, Hypnea, Lithothamnion, Meristotheca, Palmaria Grateloupia, Rhodymenia Acrosonum and Porphyra Red algae have a 60% higher absorption rate than traditional brown seaweeds

Examples of algal species which can be used in the preparation of the composition of the invention include, without limitation Grateloupia livida, Chondrυs ocellatus, Rhodymenia intricate Rhodymenia (or Palmaria) palmata (also called dulse), Acrosonum uncinatum, and Cladophora densa

b) Methods of preparation of the enriched/supplemented material

The invention relates to processes for the preparation of homotauπne-enπched and/or supplemented edible material These processes include contacting an edible absorbent material with homotaurine or a salt thereof The absorbent material is as described in the previous section

The edible absorbent material to be contacted with homotaurine is for example fresh or dried by any food process drying method (e g lyophilized, heated, smoked, and the like) and may be whole diced, chopped sliced, powdered, pureed, and the like The edible absorbent material is contacted with homotaurine in a powder form, a solution form or any other suitable form The solution or powder form of homotaurine may also comprise other ingredients including, without limitation water and/or nutrients (e g vitamins, minerals, fatty acids (DHA, EPA, and the like), plant extracts (e g a ginkgo biloba extract, etc)), and the like

For example, dried seaweed is hydrated in a solution comprising between about 1 g and about 75 g of homotaurine per 100 ml_ of water, preferably between about 5g and about 5Og per 10OmL of water The seaweed absorbs part of the homotaurine from the solution within or proximate its cells The enriched/supplemented seaweed is then optionally dried with or without being previously rinsed with fresh water The drying process is accomplished using any food-processing technique known to the skilled in the art, e g through lyophilization, or heating with or without the use of vacuum In general, homotauπne- enπched and/or supplemented seaweed are prepared to have different levels of homotaurine by treatment of different dried seaweed with aqueous homotaurine solutions of different concentrations depending on the desired content The homotaurine content in the seaweed may vary from 0 5% to 50% of the final dry seaweed preferably from 1 % to 40% An example of a process to prepare enriched/supplement seaweed is illustrated in Example 1

The resulting enriched/supplemented edible material may be consumed as is or may be seasoned, or it may be formulated for use as a nutraceutical formulation, or may be used in the preparation of foodstuffs, for example, as a food additive Enriched/supplemented algae may also be obtained by growing algae in water containing homotaurine. The process of enriching or supplementing seaweeds in nutrients (e.g calcium etc), can be done, for example, as described in Japanese patent application 213864 (Harima chemicals).

/// Compositions comprising homotaurine-enπched/supplemented edible material

Homotaurine-enriched and/or supplemented edible material may be used in the preparation of compositions, including nutraceuticals, food additives and foodstuffs. Exemplary amounts of homotaurine to be consumed or administered in one dose include milligram or microgram amounts of homotaurine (in the material or composition) per kilogram of subject or sample weight (e.g., about 50 micrograms per kilogram to about 500 milligrams per kilogram, about 1 milligram per kilogram to about 100 milligrams per kilogram, about 1 milligram per kilogram to about 50 milligram per kilogram, about 1 milligram per kilogram to about 10 milligrams per kilogram, or about 3 milligrams per kilogram to about 5 milligrams per kilogram). Additional exemplary doses include doses of about 5 mg to about 500 mg, or about 25 mg to about 300 mg, or about 25 mg to about 200 mg, about 50 mg to about 150 mg, about 10 mg to about 100 mg, about 10 mg to about 50 mg, about 20 mg to about 75 mg, or in a dose of about 50 mg, about 100 mg, about 150 mg, about 200 mg or about 250 mg, and, preferably, daily or twice daily. For comparison, exemplary doses for homotaurine per se can include about 2-3 milligram of homotaurine per kilogram of subject (twice daily) or 4-6 milligram of homotaurine per kilogram of subject (daily).

a) Food additives and foodstuffs containing same

Since homotaurine is essentially odorless and tasteless, homotaurine-enriched and/or supplemented edible material can be used in food additives and foodstuffs for increasing the uptake of homotaurine and to obtain optimal health benefit

Examples of foodstuffs which can be supplemented with homotaurine by adding the enriched or supplemented edible material of the invention to its process include, without limitation, beverages (including dry beverage powder), dairy products (e g , cheese, milk, yogurt, ice cream, etc), bakeries and pastries (e.g , breads, tortillas, pita breads, rolls, cookies, crackers, pies, cakes, nutritional bars, and the like), cereals, noodles, meat products (e.g. sausages, jerked beef, etc), fish products, egg products, nut products, soup mixes, snack foods, salad dressings, sauces, sweets, hard or soft candies, jams or jellies, seasoning (e g fine herbs, herbal salt, etc), and the like For example, enriched/supplemented material may be added as a powder in food processing or may be used as is or formulated to be used as an additive by the consumer. Algae, for example, are already used in the processing of a wide variety of food products. The enriched and/or supplemented edible algae material as described herein may replace other seaweeds in any known food process involving them.

Foodstuffs also include food for animals, such as companion pet food.

b) Nutraceutical formulations

The edible homotaurine-enriched and/or supplemented material of the invention may also be formulated into nutraceutical compositions prior to administration using techniques and procedures well known in the art. Accordingly, in another embodiment, the present invention relates to compositions comprising effective amounts of an edible homotaurine enriched/supplemented material as described herein and an acceptable vehicle, as well as methods of using and manufacturing such compositions.

The nutraceutical compositions are formulated for oral administration. Suitable acceptable vehicles include, without limitation, any non-immunogenic carrier or diluent suitable for oral administration routes.

Nutraceutical compositions of the present invention include those suitable for oral administration. The nutraceuticals may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. Methods of preparing these nutraceuticals include the step of bringing a material of the present invention into association with an acceptable vehicle (e g an inert diluent or an assimilable edible carrier) and, optionally, one or more accessory ingredients In general, the nutraceuticals are prepared by uniformly and intimately bringing a material of the present invention into association with finely divided solid carriers and then, if necessary, shaping the product. The amount of the material in such useful compositions is such that a suitable dosage will be obtained

Formulations of the invention suitable for oral administration may be in the form of capsules (e g hard or soft shell gelatin capsule), cachets, pills, tablets, lozenges, powders, granules, pellets, dragees, e.g. , coated (e.g., films or enteric coatings) or uncoated, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia), each containing a predetermined amount of a material of the present invention as an active ingredient.

In solid dosage forms of the invention for oral administration the material is, for example mixed with one or more nutraceutically acceptable carriers (subject to each country laws and regulations), such as sodium citrate or dicalcium phosphate, or any of the following: fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, or silicic acid, binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose or acacia, humectants, such as glycerol; disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, solution retarding agents such as paraffin, absorption accelerators such as quaternary ammonium compounds, wetting agents, such as, for example, cetyl alcohol and glycerol monostearate, absorbents, such as kaolin and bentonite clay, lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof, and coloring agents In the case of capsules tablets and pills, the nutraceutical compositions may also comprise buffering agents Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like Chewable tablets or else contain one or more components such as sweeteners, flavoring agents and colorants as disclosed above

Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like Other compositions useful for attaining systemic delivery of the subject agents include sublingual and buccal dosage forms Such compositions typically comprise one or more of soluble filler substances such as sucrose, sorbitol and mannitol, and binders such as acacia, microcrystalline cellulose, carboxymethyl cellulose and hydroxypropyl methyl cellulose Glidants, lubricants sweeteners, colorants, antioxidants and flavoring agents disclosed above may also be included Under ordinary conditions of storage and use, these preparations may contain a preservative to prevent the growth of microorganisms

Moreover, in certain embodiments pellets can be formulated to (a) provide for instant or rapid release of the homotaurine-enπched or supplemented material (/ e , no coating or a non-enteric film only), (b) be coated, e g , to provide for sustained release over time, or (c) be coated with an enteric coating to delay release until the nutraceutical has reached the intestinal region Examples of coatings include pH or time-dependent coatings, such that the material is released in the vicinity of a desired location, or at various times to extend the desired action Such dosage forms typically include, but are not limited to, one or more of cellulose acetate phthalate, polyvinylacetate phthalate, hydroxypropyl methyl cellulose phthalate ethyl cellulose, waxes, and shellac

The nutraceutical composition of the invention may be packaged as part of a kit, optionally including a container (e g packaging, a box, a vial, etc) The kit may be commercially used according to the methods described herein and may include instructions for use in a method of the invention IV Subiect populations

The term "subject" includes living organisms susceptible to neuronal cell death or neuronal cell loss, memory impairment, loss in verbal skills and comprehension ability, loss in planning and execution skills, etc, living organisms in need of neuroprotection or living organisms in which Aβ-amyloid-related diseases or conditions can occur. Examples of subjects include humans, chickens, ducks, Peking ducks, geese, non-human primates, deer, cows, rabbits, sheep, goats, dogs, cats, mice, rats, and transgenic species thereof The term "subject" preferably includes animals susceptible to states characterized by neuronal cell death, e g mammals, e.g. primates, e g humans The animal can be an animal model for a disease, disorder or condition. In preferred embodiments, the subject is a mammal, more preferably a human subject.

The term "human subject" also includes humans susceptible to benefit from homotaurine administration as well as other nutrient(s) present in the material, including those susceptible to or diagnosed as having an amyloid-β related disease and/or suffering from a neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, etc. The term human subject equally includes human subjects susceptible to neurodegeneration, neuronal cell loss, or neuronal cell death related or not to amyloid-β deposition, including an aging human subject. The term human subject further equally includes human subjects susceptible to memory impairment, loss in verbal skills and comprehension ability, loss in planning and execution skills, etc.

In certain embodiments of the invention, the human subject is susceptible to benefit from the methods of the invention, and is selected based on this need A subject in need includes subjects that have been identified as having a disease, disorder or condition related to β-amyloid deposition, have a symptom of such a disease or disorder, or are at risk of such a disease or disorder, and would be expected, based on diagnosis, e g , medical diagnosis, to benefit from treatment (e.g., curing, healing, preventing, alleviating, relieving, altering, remedying, ameliorating, improving, or affecting the disease or disorder, the symptom of the disease or disorder, or the risk of the disease or disorder)

For example, the human subject may be a human over 30 years old, human over 40 years old, a human over 50 years old, a human over 60 years old, a human over 70 years old, a human over 80 years old, a human over 85 years old, a human over 90 years old, or a human over 95 years old The subject may be a female human, including a postmenopausal female human, who may be on hormone (estrogen) replacement therapy The subject may also be a male human. In another embodiment, the subject is under 40 years old. Individuals having or being predisposed to memory or cognitive impairment, age- associated memory impairment or mild cognitive impairment, or forms of dementia, can be identified, for example, by the Clinical Dementia Rating (CDR) scale Mini-mental State Examination (MMSE) Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS- Cog) or any other test known in the art, as discussed herein Baseline scores on suitable metrics including the MMSE and the ADAS together with other metrics designed to evaluate a more normal population can be used to find an at risk population Another method for identifying an at risk group utilizes an assay for neural thread protein in the urine, see, e g , Munzar et al , Neurology and Clinical Neurophysiology, VoI 2002, No 1 Patients with high risk for Alzheimer's Disease can also be selected from a population by screening for early signs of memory loss or other difficulties associated with pre-Alzheimer's symptomatology, a family history of Alzheimer's Disease, patients with Mild Cognitive Impairment (MCI), genetic risk factors age, sex and other features found to predict high-risk for Alzheimer's Disease

The term "prevention" or "preventing" is also used to describe the administration of a material or composition of the invention to a subject who is at risk of (or susceptible to) such a disease or condition Subjects amenable to treatment for prevention of the disease or condition include individuals at risk of the disease or condition but not showing symptoms, as well as patients presently showing symptoms Virtually anyone is at risk of developing a condition related to Amyloid-β, or neurodegeneration if he or she lives long enough Therefore, the present methods can be administered prophylactically to the general population without any assessment of the risk of the subject patient The present methods are also useful for individuals who do have a known risk of Alzheimer's disease Such individuals include those having relatives who have experienced this disease, and those whose risk is determined by analysis of genetic or biochemical markers, including brain plaques diagnosed by imaging methods, e g , MRI, PET, SPECT etc Examples of such imaging methods are discussed in Burggren et al Current Topics in Medicinal Chemistry, vol 2002, no 2, pp 385-393, and Sair et al , Neuroradiology, vol 46, pp 93-104 (2002) Alzheimer's disease predisposing factors identified or proposed in the scientific literature include, among others, a genotype predisposing a subject to Alzheimer's disease, environmental factors predisposing a subject to Alzheimer's disease past history of infection by viral and bacterial agents predisposing a subject to Alzheimer's disease, and vascular factors predisposing a subject to Alzheimer's disease Genetic markers of risk toward Alzheimer's disease include mutations in the APP gene, particularly mutations at position 717 and positions 670 and 671 referred to as the Hardy and Swedish mutations respectively (see Hardy et al , TINS 20, 154-158 (1997)) Other markers of risk are mutations in the presenilm genes, PS1 and PS2, and ApoE4, family history of AD, hypercholesterolemia or atherosclerosis The subject may be shown to be at risk by a diagnostic brain imaging technique, for example, one that measures brain activity, plaque deposition, or brain atrophy The human subject may also be shown to be at risk by a cognitive test such as Clinical Dementia Rating ("CDR"), Alzheimer's disease Assessment Scale-Cognition ("ADAS-Cog") Disability Assessment for Dementia ("DAD") or Mini-Mental State Examination ("MMSE") and/or by a subscale of any of the above test (e.g. a subset of tests related to memory function or cognitive function) or any other cognition or memory test known in the art.

In another embodiment, the human subject exhibits no symptoms of Alzheimer's disease. In another embodiment, the subject is at least 40 years of age and exhibits no symptoms of Alzheimer's disease. In another embodiment, the human subject is at least 50 years of age and exhibits no symptoms of Alzheimer's disease.

V. Methods of use of the materials and compositions of the invention Another aspect of the invention pertains to a method for inhibiting neuronal cell death by administering an effective amount of a homotaurine enriched/supplemented material or composition of the present invention. In yet another aspect, the invention pertains to a method for providing neuroprotection to a subject having an Aβ-amyloid related disease or condition which includes the step of administering to (or consuming by) a subject, an effective amount of a material or composition of the present invention, such that neuroprotection is provided. As used herein, the term "neuroprotection" includes protection of neuronal cells of a subject from cell death that may result in initiation of processes such as, but not limited to: the destabilization of the cytoskeleton; DNA fragmentation; the activation of hydrolytic enzymes, such as phospholipase A2; activation of caspases, calcium- activated proteases and/or calcium-activated endonucleases; inflammation mediated by macrophages; calcium influx into a cell; membrane potential changes in a cell; the disruption of cell junctions leading to decreased or absent cell-cell communication; and the activation of expression of genes involved in cell death.

According to a preferred embodiment, the materials and compositions of the present invention are used for one or more of the following: to protect memory function, to protect the brain structure associated with memory and learning, to sustain brain cells health, to maintain verbal skills and comprehension ability, to support planning and execution skills, to treat or prevent an amyloid-β related disease or condition, to regulate production of or levels of amyloid β (Aβ) peptides, and to prevent, reduce, or inhibit amyloid deposition in a subject The materials and compositions of the invention may act to ameliorate the course of a disease or condition using any of the following mechanisms (this list is meant to be illustrative and not limiting): protecting neurons from induced neuronal toxicity, slowing the rate of β-amyloid fibril formation or deposition; lessening the degree of β-amyloid deposition; inhibiting, reducing, or preventing amyloid fibril formation; inhibiting neurodegeneration or cellular toxicity induced by β-amyloid; inhibiting amyloid induced inflammation in the brain; enhancing the clearance of β-amyloid from the brain; enhancing degradation of Aβ in the brain, or favoring clearance of amyloid protein prior to its organization in fibrils, and decreasing the ratio of Aβ42 Aβ40 in the CSF or plasma In another embodiment, the invention pertains to a method for improving or preserving cognition and/or memory function in a subject The method includes administering an effective amount of a material or composition of the invention, such that the subject's cognition and/or memory function is improved or preserved The subject's cognition can be tested using methods known in the art such as "CDR' , "MMSE", "DAD" and "ADAS-Cog", or a subscale thereof (e g a subset of tests measuring memory or cognition related aspects) Improvement or protection of cognition or memory is present within the context of the present invention if there is a measurable difference between the performances of subjects treated using the methods of the invention as compared to members of a placebo group historical control, or a group using a non-enriched/supplemented equivalent material, or between subsequent tests given to the same subject The invention also pertains to a method for treating, slowing or stopping a β-amyloid related disease or condition associated with cognitive or memory impairment, by administering to a subject an effective amount of a material or composition of the invention, wherein the annual deterioration of the subject's cognition as measured by any of the foregoing mentioned test is improved or stabilized

By using the methods and compositions of the present invention the levels of amyloid β peptides in a subject's plasma or cerebrospinal fluid (CSF) could be significantly reduced from levels prior to treatment from about 10 to about 100 percent, or even about 50 to about 100 percent, e g 15, 25, 40, 60, 70, 75, 80, 90, 95 or 99% Accordingly, in certain embodiments, the human subject can have an elevated level of amyloid Aβ₄₀ and Aβ₄₂ peptide in the blood and/or CSF prior to a treatment according to the present methods, e g Aβ₄₀ levels of greater than about 10 pg/ml_, or greater than about 20 pg/mL, or greater than about 35 pg/mL, or even greater than about 40 pg/mL and Aβ₄₂ levels 30 pg/mL to about 200 pg/mL, or even to about 500 pg/mL Similarly, according to some embodiments, the methods and compounds of the present invention help reduce the size and/or number of Aβ plaques or Aβ deposits in the brain from about 10 to about 100 percent, or even about 50 to about 100 percent e g , 15, 25, 40 60, 70, 75, 80, 90, 95 or 99%, when compared to levels prior to treatment Also, by using the methods of the invention, the healthy cognitive and memory functions may be enhanced stabilized, improved, or decline may be prevented, as well as general well-being of the individual

In one embodiment, the composιtιon(s) of the invention is administered at a nutraceutically effective dosage for the prevention or treatment of age-associated memory impairment, mild cognitive impairment, mιld-to-moderate cognitive impairment, brain aging, or memory loss A ' nutraceutically effective" dosage stabilizes cognitive and/or memory functions or prevents a further decrease in cognitive and/or memory function (/ e , preventing, slowing, or stopping progression)

It is to be understood that wherever values and ranges are provided herein, e g , in ages of subject populations, dosages, and blood levels, all values and ranges encompassed by these values and ranges, are meant to be encompassed within the scope of the present invention Moreover, all values in these values and ranges may also be the upper or lower limits of a range

Vl Combination therapy In certain embodiments, the materials and compositions according to the invention can be used concomitantly with at least one therapeutic agent or at least one additional nutraceutical agent The compositions according to the invention and the at least one other agent(s) can act additively or, in certain embodiments, synergistically In certain embodiments the compositions of the invention can be administered concurrently with the administration of the other agent In certain embodiments, the compositions of the invention can be administered prior or subsequent to administration of the other agent The at least one other agent can be effective for treating the same or different disease, disorder, or condition

Methods of the present invention include administration of one or more materials or compositions of the present invention and one or more therapeutic or one or more other nutraceutical agents provided that the combined administration does not inhibit the efficacy of any of the active ingredients and/or does not produce adverse combination effects

In certain embodiments, compositions of the present invention can be administered concurrently with the administration of at least one therapeutic or another nutraceutical agent, which can be part of the same composition as, or in a different composition from, that containing the materials of the present invention In certain embodiments, the combination therapy comprises alternating between administering a composition of the present invention and a composition comprising at least one therapeutic or another nutraceutical agent, e g , to minimize adverse side effects associated with a particular agent When a material or composition of the present invention is administered concurrently with another agent that potentially can produce adverse side effects including, but not limited to, toxicity, the therapeutic agent can advantageously be administered at a dose that falls below the threshold at which the adverse side effect is elicited

In certain embodiments, a composition can further comprise substances to enhance, modulate and/or control release, bioavailability, efficacy, potency, stability, and the like For example, to enhance nutraceutic effect of homotaurine, the composition can be coadministered with one or more active agents to increase the absorption or diffusion of homotauπne from the gastrointestinal tract, or to inhibit degradation thereof in the systemic circulation. In certain embodiments, a material or composition of the present invention can be co-administered with active agents having a pharmacological effect that enhance the health benefits of homotauπne. In certain embodiments, materials or compositions of the present invention include, or can be administered to a subject together with, a therapeutic drug that may be available over-the-counter or by prescription. US patent application No. 2005/0031651 (incorporated herein by reference) provide a long but non-exhaustive list of "therapeutic drugs" that can be useful, in combination, according to the invention. Examples of therapeutic drugs to be used with the compositions of the present invention are useful in the prevention or treatment of Alzheimer's Disease or its symptoms, including but not limited to cholinesterase inhibitors, e.g. donepezil (Aricept™), rivastigmine (Exelon™), galanthamine (Reminyl™), NMDA receptor antagonists, e.g. memantine (Namenda™), and others, e.g. R-flurbiprofen (Flurizan™). The compositions according to the invention can also be combined with vaccines and antibodies for the prevention or treatment of AD. The composition can also be combined with other natural products, nutrients and supplements, including, without limitation, vitamins and minerals, polyunsaturated fatty acids of the Omega group (e g omega 3, 6 and/or 9), galanthamine (also as a nutraceutical), gotu kola, dimethylaminoethanol, and extracts of Ginkgo biloba.

VII Standard methods for testing the compositions and materials of the invention.

The materials and compositions according to the invention can be further analyzed, tested or validated using a variety of in vitro or in vivo assays to confirm their safety, bioavailability, neuroprotection, their ability to deliver homotaurine etc. Assays for assessing these parameters and activity are widely described in the literature and are part of the general knowledge and expertise of the skilled in the art

a) Neuroprotection

Biological assays can be conducted to assess whether a composition has a protective effect against neuronal injury, stress or induced toxicity. Examples of biological assays include "morphological changes" (e g plasma membrane blebbing, cell shape change, loss of substrate adhesion properties, etc), "altered membrane permeability" (e g using vital dyes (e.g., propidium iodide and trypan blue), see also, e. g., Haugland, 1996

Handbook of Fluorescent Probes and Research Chemicals, 6th ed., Molecular Probes, OR), "dysfunction of mitochondrial membrane potential" (see, e.g., Haugland, 1996 Handbook of

Fluorescent Probes and Research Chemicals, 6th ed., Molecular Probes, OR, pp 266-274 and 589- 594, Kamo et al. (1979) J Membrane Biol. 49:105, Quinn (1976) The Molecular Biology of Cell Membranes, University Park Press, Baltimore, Md., pp 200-217, and PCT publication WO 00/19200 to Dykens et al), "caspase activation" (see, e g , Ellerby et al (1997) J. Neurosci. 17:6165; Kluck, et al. (1997) Science 275: 1132, Nicholson et al. (1995) Nature 376:37; Rosen and Casciola- Rosen (1997) J. Cell Biochem. 64 50; U.S. Pat. No. 5,976,822; Mahajan, et al. (1999) Chem. Biol. 6:401-9; and Xu, et al. (1998) Nucl Acids Res. 26:2034-5), "cytochrome C release" (see, e.g., Liu et al. (1996) Cell 86: 147), "assays for cell lysis" (see, e g PCT publication WO 00/70082), "ischemic model systems" (see, e.g., Aarts et al , Science 298:846-850, 2002; Longa, E. Z. et al (1989) Stroke 20:84; Belayev, L., et al (1996) Stroke 27:1616; Bederson, J. B. et al. (1986) Stroke 17.472, and De Ryck, M et al. (1989) Stroke 20 1383), "MTT cytotoxicity assay" (e.g., using the 3-(4,5-dιmethylthιazol-2- yl)-2,5-dιphenyl tetrazohum bromide (MTT) assay (Trevigen, Gaithersburg, Md.)), "trypan blue cell viability measurement" (see e.g. Yao et al., Brain Res., 889, 181-190 (2001 )), and "Determination of Cellular ATP Levels" (e.g. using the ATPLite-M® luminescence assay (Packard BioSciences Co.), and the ATP concentrations are measured on a TopCount NXT® counter (Packard BioSciences Co.))

b) Gastrointestinal absorption

The compositions according to the invention can be further analyzed, tested or validated for their ability to get homotauπne absorbed by the gut and/or intestine if so desired

Intestinal permeability and transport of homotaurine may be estimated using a variety of in vitro, in situ, as well as in vivo models (Balimane et al. (2000) J Pharmacol Toxicol Methods 44:385-401 ; Hidalgo I. (2001) Curr Top Med Chem 1 :385-401 , Hillgreen K, Kato A and Borchardt R. (1995) 15:83-109)

For instance, parallel artificial membrane permeability (PAMPA) assay and cell- based systems such as Caco-2 and Mardin-Darby canine kidney (MDCK) cells are the most frequently used in vitro models.

An in situ study such as an intestinal perfusion could also be performed to assess homotaurine absorption. Typically, a whole animal absorption study (pharmacokinetic study) will be performed in parallel with the in vitro and/or in situ studies to assess intestinal permeability In general, absorption in animals is believed to be a good predictor of absorption in humans.

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures, embodiments, claims, and examples described herein. Such equivalents are considered to be within the scope of this invention and covered by the claims appended hereto. The contents of all references, issued patents, and published patent applications cited throughout this application are hereby incorporated by reference. The invention is further illustrated by the following examples, which should not be construed as further limiting.

EXAMPLES

Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, concentrations, properties, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about." At the very least, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques Accordingly, unless indicated to the contrary, the numerical parameters set forth in the present specification and attached claims are approximations that may vary depending upon the properties sought to be obtained. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the embodiments are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contain certain errors resulting from variations in experiments, testing measurements, statistical analyses and such.

The present invention also relates to novel compositions and the preparation thereof. The following detailed examples describe how to prepare the various compositions and/or perform the various processes of the invention and are to be construed as merely illustrative, and not limitations of the preceding disclosure in any way whatsoever. Those skilled in the art will promptly recognize appropriate variations from the procedures both as to solvents, proportions, components, and as to conditions and techniques. In some cases, the components may be commercially available

Example 1:

Accordingly, the following example is presented to illustrate how homotauπne- enriched/supplemented materials according to the invention are prepared

Preparation ofhomotaurine-enriched/supplemented algae

Non-crushed, non-washed commercial dry alga (laver, Porphyra) was placed in an aqueous solution of homotaurine (HT to water; from 0:1 to 0.5: 1 , wt /vol., see Table 1) The volume (ml.) of water used was 15 times the weight (g) of dry alga starting material The mixture was kept at room temperature for 4 h with occasional stirring, without breaking the leaves The excess aqueous solution was removed (drained) The re-hydrated alga was rinsed twice briefly by dipping into cold water (about 50 times volume (ml_) of water to the initial weight (g) of the alga), drained thoroughly by spreading in a mesh-bottom container, air- dried at room temperature for 2 days, and dried under vacuum at 40 ⁰C until a constant weight was obtained (about 40 h, recording the final weight). Results from exemplary experiments are given in Table 1.

Table 1. Treatment of commercial laver³ with HT in aqueous solution

a. A product of Haizhilin, a brandname from a Chinese company b Starting weight of dry alga. c. Homotaurine content in g in the volume of water used for hydration of the dry alga d. Weight obtained after drying of the homotaurine-enπched/supplemented alga e Weight change for homotauπne-treated laver was based on the final weight from blank; the weight-gain was mainly due to the absorption of homotaurine by the laver.

Example 2:

Accordingly, the following example is presented to illustrate how homotaurine release from homotaurine-enriched/supplemented materials can be measured. The goal is to determine the rate of homotaurine release in different media, so as to mimic further processing conditions as well as gastrointestinal release.

Homotauήne-release from homotaurine-enriched/supplemented algae An amount of 5 g of the homotauπne-enriched/supplemented laver from example 1 (Table 1, experiment no 2) was placed in pH-adjusted (with HCI) water (300 mL). The mixture was stirred slowly. Aliquot of liquid were withdrawn at different time points, and diluted with water to 1000 times of dilution, followed by further dilution with equal volume of acetonitrile, and then analyzed for its homotaurine content using LC-MS. The results obtained for pH 6.9 and 2.0 after 5, 10 and 15 minutes are shown in Table 2.

Table 2. Homotaurine release from homotaurine-enriched/supplemented laver

^* The concentration and the amount were apparent value obtained from a standard curve obtained using an aqueous homotaurine solution It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims.

Claims

1 A homotauπne-enπched or supplemented edible material, comprising an absorbent material in combination with homotauπne, or a suitable salt thereof

2 The material of claim 1 , wherein said absorbent material is selected from plants, algae, fungi and animal products

3 The material of claims 1 or 2, wherein said absorbent material comprises plants or algae

The material of claim 3, wherein said absorbent material comprises algae

5 The material of claim 4, wherein said absorbent comprises a red, green or brown alga

6 The material of claim 5, wherein said algae comprises red seaweed

7 The material of claim 6, wherein said red seaweed comprises a seaweed of a genera selected from the group consisting of Chondrus, Eucheuma, Gigartina, Gracilaria,

Hypnea Lithothamnion, Meπstotheca, Palmaπa, Grateloupia Rhodymenia, Acrosoπum and Porphyra

8 The material of claim 7, wherein said red seaweed comprises a seaweed of a species selected from the group consisting of Grateloupia livida, Chondrus ocellatus,

Rhodymenia intricate, Rhodymenia palmata, and Acrosoπum uncinatum

9 The material of claim 5, wherein said algae comprises brown seaweed

10 The material of claim 9, wherein said brown seaweed comprises a seaweed of a genera selected from the group consisting of Alaria, Ascophyllum, Durvillaea, Eisenia, Fucus, Himanthalia, Hizikia Laminaria, Macrocystis, Sargassum and Undana

1 1 The material of claim 5, wherein said algae comprises green seaweed

12. The material of claim 11 , wherein said green seaweed comprises a seaweed of a genera selected from the group consisting of Caulerpa, Codium, Enteromorpha, Monostroma, Cladophora and UIv a

13. The material of claim 12, wherein said green seaweed is a seaweed of the species Cladophora densa

14. The material of claim 4, wherein said alga comprises an alga of a genera selected from the group consisting of Spirulina and Chlorella.

15. The material of any one of claims 1 to 14, wherein said material comprises from about 0 2% to about 60% (w/w) of homotauπne in the material.

16. The material of claim 15, wherein said material comprises from about 0.5% to about 50% (w/w) of homotaurine in the material

17. The material of claim 16, wherein said material comprises from about 1% to about 40% (w/w) of homotaurine in the material

18. A composition comprising a homotaurine-enπched or supplemented edible material according to any one of claim 1 to 17 and an acceptable carrier

19. A nutraceutical composition comprising a homotaurine-enriched or supplemented edible material according to any one of claim 1 to 17

20. A food additive comprising a homotaurine-enriched or supplemented edible material according to any one of claim 1 to 17

21. A foodstuff comprising a homotaurine-enriched or supplemented edible material according to any one of claim 1 to 17.

22 Use of the homotaurine-enriched or supplemented edible material according to any one of claim 1 to 17, for providing neuroprotection

23 The use of claim 22, wherein against said neuroprotection is for protecting neuronal cells from toxicity induced by Amyloid-β amyloidogenic proteins or peptides.

24. The use of claim 23, wherein said proteins or peptides are soluble Amyloid-β.

25. Use of the homotauπne-enriched or supplemented edible material according to any one of claim 1 to 17, for improving or preserving cognitive and/or memory function.

26. Use of the homotaurine-enriched or supplemented edible material according to any one of claim 1 to 17, for protecting the brain structure associated with memory and learning.

27. Use of the homotaurine-enriched or supplemented edible material according to any one of claim 1 to 17, for sustaining brain cells health.

28. Use of the homotaurine-enriched or supplemented edible material according to any one of claim 1 to 17, for maintaining verbal skills and comprehension ability.

29. Use of the homotaurine-enriched or supplemented edible material according to any one of claim 1 to 17, for supporting planning and execution skills

30. Use of homotaurine-enriched or supplemented edible material according to any one of claim 1 to 17, for treating or preventing a disease or condition in which Amyloid-β proteins or peptides are present.