JP2002020403A - Novel polysaccharide inducible for apoptosis and use thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a natural substance-derived polysaccharide which is useful for the prevention and medical treatment for diseases having a relation with an apoptosis induction and which has non- or extremely low toxicity to normal cells. SOLUTION: The apoptosis-inducible polysaccharide and a composition containing the polysaccharide inducible selectively for an apoptosis to abnormal cells, undesirable to a living body, results from a water-extract from seaweeds. Furthermore, this invention has also relations to the medicinal compositions and food products containing the above polysaccharide or the above composition.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel polysaccharide capable of selectively inducing apoptosis in abnormal cells that are not desirable for a living body such as cancer cells (hereinafter, sometimes simply referred to as “apoptosis-inducing polysaccharide”), Fractions of the seaweed aqueous extract containing the polysaccharide, pharmaceutical compositions containing them as active ingredients, particularly for diseases in which apoptosis induction is effective (for example, autoimmune diseases such as cancer, colorectal polyposis, rheumatism, and viral infections) It relates to a pharmaceutical composition for prevention and treatment. The present invention also relates to a health food comprising the polysaccharide or the polysaccharide-containing composition.

[0002]

2. Description of the Related Art Cell death controlled by a gene called apoptosis is caused by morphological changes in the ontogeny of higher animals, establishment of a nervous system network, maintenance of endocrine system homeostasis in mature individuals, and immune system. It plays an important role in basic life phenomena such as the establishment of diversity and specificity. Apoptosis is deeply involved not only in such physiological phenomena but also in the development of various disease states such as cancer, viral infections such as AIDS, neurological diseases such as Alzheimer's disease, and autoimmune diseases such as rheumatoid arthritis. Things are becoming increasingly apparent. For such diseases involving apoptosis, compounds that induce apoptosis selectively in the pathogenic cells and have little toxicity to normal cells are being actively searched for. Such promising compounds have been screened. However, at present it has not been linked to the establishment of treatment and prevention methods using such compounds.

[0003]

Accordingly, an object of the present invention is to provide a novel compound which has a selective apoptosis-inducing ability for pathogenic cells such as cancer cells and virus-infected cells and has a wide safety margin for living organisms. Another object of the present invention is to provide a medicament for effective and safe prevention and treatment of various diseases caused by the above-mentioned pathogenic cells, by screening from natural products and using the compound. Another object of the present invention is to provide a health food comprising the novel compound.

[0004]

DISCLOSURE OF THE INVENTION The present inventors have widely pursued a search for a compound having an apoptosis-inducing activity and almost no toxicity from natural products in a study for artificially controlling apoptosis. . The results of research in this field have revealed that a special structure of a natural polysaccharide has apoptosis-inducing ability. In the present invention,
The present inventors have focused on seaweeds such as mekabu, kelp, mozuku, and funori, and have attempted to obtain a polysaccharide having a desired apoptosis-inducing ability from these seaweeds. as a result,
It has been found that a substance that induces apoptosis selectively in a water extract of seaweed with respect to pathogenic cells of a disease involving apoptosis such as cancer cells exists. Next, the present inventors fractionate and purify the substance by ultrafiltration and carry out structural analysis to reveal that the active ingredient is a novel polysaccharide having a different constituent sugar composition from the conventionally known polysaccharide. I made it.
Furthermore, the present inventors have confirmed that the novel polysaccharide can selectively induce apoptosis in cancer cells even in vivo in cancer-bearing animal experiments and exert an antitumor effect, thereby completing the present invention. Reached.

That is, the present invention provides one or more fractions obtained by fractionating a water extract of seaweed on the basis of a difference in molecular weight, and selectively apoptosis to abnormal cells which are not desirable for a living body. A composition comprising a polysaccharide that induces In a preferred embodiment, the composition has a molecular weight of 5,000 to 100,0.
00, more preferably a molecular weight of 50,000
~ 100,000 fractions. In such a fraction, the following saccharide composition: (1) a molar ratio of galactose, fucose, mannose of 1: 0.4 ± 0.1: 0.3 ± 0.05 (2) glucuronic acid 0.6 to 1 galactose
Included are apoptosis-inducing polysaccharides of the invention having a molar ratio of 1.0.

The apoptosis-inducing polysaccharide of the present invention and a seaweed-derived composition containing the polysaccharide can induce apoptosis selectively on abnormal cells that are undesirable for the living body, and thus prevent diseases caused by these cells. And is effective for treatment. Therefore, the present invention also comprises a pharmaceutically effective amount of an apoptosis-inducing polysaccharide or a seaweed-derived composition containing the polysaccharide, such as cancer, autoimmune disease, neurological disease, viral infection, radiation exposure disorder and the like. Provided is a pharmaceutical composition for preventing and treating diseases.

The apoptosis-inducing polysaccharide and the seaweed-derived composition containing the polysaccharide of the present invention are edible extracts from seaweed and fractionated and purified products thereof, or equivalents thereof, so that they can be safely edible. It can be used as a liposome and can achieve the preventive effect of the above-mentioned diseases by oral ingestion on a daily basis. Therefore, the present invention also provides a food product comprising the apoptosis-inducing polysaccharide of the present invention or a seaweed-derived composition containing the polysaccharide.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The "apoptosis-inducing polysaccharide" of the present invention is capable of selectively inducing apoptosis in abnormal cells that are not desirable for a living body, and has the following properties: (1) molecular weight: 5, (2) The molar ratio of galactose, fucose and mannose is 1: 0.4 ± 0.1: 0.3 ± 0.05. (3) Glucuronic acid is added to galactose at 0 .6 ~
There is no particular limitation as long as it has a molar ratio of 1.0, but preferably the following properties: (4) Gas under certain conditions (the details of the conditions are described in Example 5 below) In chromatography, retention time 1
It shows peaks at 1.9 minutes and 13.1 minutes, and contains the substance corresponding to the former in a molar ratio of 200 ± 50 to galactose 1 and the substance corresponding to the latter in a molar ratio of 10 ± 5 to galactose 1 ( 5) It further contains a sulfate group in a molar ratio of 0.9 to 1.5 with respect to the neutral sugar 1.

The “apoptosis-inducing polysaccharide” of the present invention may be of any origin. For example, seaweeds, preferably seaweeds belonging to red algae or brown algae, more preferably seaweeds, kelpaceae and mozukuaceae. And seaweeds belonging to the family Noriaceae, particularly preferably from seaweed, most preferably from seaweed (a site where thick and short pleats gather near the roots set on the rocks of seaweed).

In the present invention, "abnormal cells undesired in living organisms" refers to abnormal cells that cause a disease in which apoptosis develops or is greatly involved in its suppression, such as cancer cells in cancer and autoreactions in autoimmune diseases. Sexual cells, virally infected cells in viral infections,
Examples include abnormal nerve cells in a neurological disease and radiation-exposed cells in a radiation-exposed disorder. Preferably, the "abnormal cells undesired for the living body" are cancer cells, and more preferably, breast cancer cells, glioma cells, and the like.

[0011] More preferably, the apoptosis-inducing polysaccharide of the present invention has a molecular weight of 50,000 to 100,000.

The apoptosis-inducing polysaccharide of the present invention can be prepared by the following method using seaweeds such as seaweed (especially mekabu), kelp, mozuku, and funori as raw materials. First, the dried seaweed is finely pulverized using a pulverizer or the like, an appropriate amount of water is added to the pulverized product, and the mixture is sufficiently mixed, and then left at 4 to 30 ° C, preferably 4 to 10 ° C for 15 to 25 hours. And extract. After removing the precipitate by centrifugation or the like, the supernatant is passed one or several times through a 100 to 0.45 μm nylon mesh or filter paper (while gradually reducing the pore size as necessary). The obtained filtrate is subjected to ultrafiltration, and fractionated into, for example, fractions having a molecular weight of 100,000 to 100,000 to 50,000, 50,000 to 5,000 and 5,000 or less, thereby obtaining the above-mentioned molecular weight and sugar. An apoptosis-inducing polysaccharide having a composition can be obtained. The obtained fraction can be used and stored as a stock solution, diluted or concentrated, or dried or lyophilized, depending on the use.

[0013] The present invention also provides one or more fractions obtained by fractionating a water extract of seaweed based on a difference in molecular weight, and selectively apoptosis to abnormal cells that are undesirable for a living body. There is provided a composition comprising a triggering polysaccharide. That is, the fractionated purified product of the seaweed aqueous extract obtained by the above method is not only a fraction of the molecular weight of 100,000 to 50,000 and 50,000 to 5,000 containing the apoptosis-inducing polysaccharide of the present invention, Fractions having a molecular weight of 100,000 or more and fractions having a molecular weight of 5,000 or less also have apoptosis-inducing ability.
The saccharide composition of the polysaccharide contained in the fraction having a molecular weight of 100,000 or more is close to the saccharide composition in the unextracted aqueous extract of seaweed, and is considered to be the most abundant of the seaweed polysaccharide. On the other hand, the saccharide composition of the polysaccharide contained in the fraction having a molecular weight of 5,000 or less is similar to the saccharide composition of the polysaccharide contained in the fraction having a molecular weight of 50,000 to 5,000. In the present invention, the “polysaccharide” refers to a saccharide formed by dehydration bonding of at least 10 molecules of monosaccharides (including derivatives such as sugar alcohols and uronic acids). Therefore, the “apoptosis-inducing polysaccharide-containing composition derived from a seaweed water extract” of the present invention must be a fraction containing a molecular weight at least containing a polysaccharide as defined above.

The “apoptosis-inducing polysaccharide-containing composition derived from a seaweed water extract” of the present invention may be derived from any seaweed, but is preferably a seaweed belonging to a red algae or brown algae, more preferably a seaweed. Laminariaceae, Oataceae,
It is derived from seaweed belonging to Funori family and the like, particularly preferably from seaweed, and most preferably from seaweed.

The “composition containing apoptosis-inducing polysaccharide derived from a seaweed water extract” of the present invention is preferably derived from a fraction containing the apoptosis-inducing polysaccharide of the present invention, and therefore has a molecular weight of 5,000 to 100,000. ,
More preferably, it is derived from a fraction having a molecular weight of 50,000 to 100,000.

The present invention also provides a pharmaceutical composition containing the "apoptosis-inducing polysaccharide" of the present invention or the "apoptosis-inducing polysaccharide-containing composition derived from a seaweed water extract" of the present invention in a pharmaceutically effective amount. I do. Since the “apoptosis-inducing polysaccharide” of the present invention or the “apoptosis-inducing polysaccharide-containing composition derived from a seaweed water extract” of the present invention can induce apoptosis selectively in abnormal cells that are undesirable for a living body, The pharmaceutical composition can be used for preventing and treating diseases caused by the abnormal cells. Examples of such diseases include cancers such as breast cancer and glioma, leukemia, colon polyposis, autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, inflammatory diseases such as ulcerative colitis and Sjogren's syndrome, Huntington's disease, Neurological diseases such as Alzheimer's disease, Parkinson's disease, Down's syndrome, amyotrophic lateral sclerosis, HIV, HBV, HCV, adenovirus, poxvirus, herpes virus, papovavirus and other viral infections, and radiation of several Gy or more Exposure disorders and the like. Preferably, it is a pharmaceutical composition for preventing and treating cancer, particularly breast cancer, glioma and the like.

The “apoptosis-inducing polysaccharide” of the present invention or the “apoptosis-inducing polysaccharide-containing composition derived from seaweed water extract” of the present invention may contain, if necessary, a pharmaceutically acceptable carrier (eg, an excipient, Diluent, etc.) and can be appropriately mixed with the necessary components such as liquid preparations, powders, granules, tablets, capsules, syrups, injections, aerosols, etc. It can be administered orally.

Examples of the pharmaceutically acceptable carrier include:
Excipients such as sucrose, starch, mannitol, sorbitol, lactose, glucose, cellulose, talc, calcium phosphate, calcium carbonate, cellulose, methylcellulose, hydroxypropylcellulose, polypropylpyrrolidone, gelatin, gum arabic, polyethylene glycol, sucrose , A binder such as starch, starch, carboxymethylcellulose, hydroxypropyl starch,
Disintegrants such as sodium-glycol-starch, sodium bicarbonate, calcium phosphate, calcium citrate, magnesium stearate, aerosil, talc,
Lubricants such as sodium lauryl sulfate, citric acid, menthol, glycyrrhizin ammonium salt, glycine, aromatic powders such as orange powder, preservatives such as sodium benzoate, sodium bisulfite, methylparaben, propylparaben, citric acid, sodium citrate, Stabilizers such as acetic acid,
Methylcellulose, polyvinylpyrrolidone, suspending agents such as aluminum stearate, dispersants such as surfactants,
Examples include, but are not limited to, water, physiological saline, diluents such as orange juice, cocoa butter, polyethylene glycol, and base wax such as white kerosene.

Preferably, the formulation of the present invention is an oral or injectable formulation. Formulations suitable for oral administration dissolve an effective amount of "apoptosis-inducing polysaccharide" or "apoptosis-inducing polysaccharide-containing composition derived from seaweed water extract" in a diluent such as water, saline, or orange juice. Solution, capsule, sachet or tablet containing an effective amount of the substance as a solid or granule, suspension of an effective amount of the substance in a suitable dispersion medium, effective amount of the substance And an emulsion obtained by dispersing and emulsifying a solution in which is dissolved in an appropriate dispersion medium.

Formulations suitable for parenteral administration include aqueous and non-aqueous isotonic sterile injection solutions, which include antioxidants, buffers, bacteriostats, isotonic agents and the like. May be included. Aqueous and non-aqueous aseptic suspensions may also be mentioned, which may contain suspending agents, solubilizers, thickeners, stabilizers, preservatives and the like. The preparation of the present invention
A unit dose or a plurality of doses can be enclosed in a container like an ampoule or a vial. In addition, an effective amount of “apoptosis-inducing polysaccharide” or “composition containing apoptosis-inducing polysaccharide derived from seaweed water extract” and a pharmaceutically acceptable carrier are freeze-dried (freeze-dried), and an appropriate sterile It may be stored in a state in which it may be dissolved or suspended in a vehicle.

The dose of the pharmaceutical composition of the present invention is determined by the effective amount of the apoptosis-inducing polysaccharide as an active ingredient, the cytotoxicity of the substance, the type of disease, the progress of the disease, the drug receptivity of the administration subject, the body weight, Depending on the age and the like, for example, in the case of oral administration, the amount of polysaccharide as an active ingredient is usually 1 to 1,0.
00 mg / kg of body weight, and this amount can be administered once or several times a day.

The “apoptosis-inducing polysaccharide” and “composition containing apoptosis-inducing polysaccharide derived from seaweed water extract” of the present invention are those which have been conventionally safely taken as food or equivalents thereof. LD compared to quantity
It is a substance with an extremely high ₅₀ value and a wide safety margin. (Here, “equivalents” are obtained from non-edible seaweeds or raw materials other than seaweed, but substantially equivalent to those obtained from edible seaweed as substances. The same thing). Therefore, the “apoptosis-inducing polysaccharide” and the “apoptosis-inducing polysaccharide-containing composition derived from a seaweed water extract” of the present invention can be used not only as a medicament but also alone or together with an acceptable food additive. It can also be used as food such as food. Acceptable food additives include commonly used preservatives, colorants, flavors, stabilizers and the like.
In addition, it can be mixed with other nutrients such as sugars, proteins, lipids, amino acids, vitamins, iron, calcium, magnesium, and dietary fiber to obtain a multifunctional nutritional food.

[0023]

The present invention will be described in more detail with reference to the following examples, which are merely illustrative and do not limit the scope of the present invention in any way.

Example 1 Preparation of Mekabu Water Extract Freeze-Dried Powder (Mekabu Polysaccharide) Mekabu (Sanriku dried mekabu) was crushed for 1 minute at 15,000 rpm using a blender crusher to obtain Mekabu powder. Was. Next, 1 g of water was added to 10 g of Mekabu powder.
L was added, mixed well, and allowed to stand at 4 ° C. for 24 hours.
The precipitate was removed by high-speed centrifugation (3,000 rpm, 5 minutes), and the supernatant was recovered. The solution was passed through a nylon mesh 70 μm and 45 μm once each. Further Wh
After passing once through an atman GD / X (0.45 μm) filter, fractions having a molecular weight of 100,000 or less were collected by ultrafiltration, and lyophilized to a powder (mekabu polysaccharide).

Example 2 Apoptosis-Inducing Activity of Mekabu Polysaccharide on Cancer Cell Culture A 9,10-dimethylbenzanthracene (DMBA) -induced rat breast cancer cell culture was cultured in a 60 mm Petri dish at 5 × 10 5
⁵ plated so that the cells / ml, CO ₂ - incubator, 37 ° C., was cultured overnight at 5% CO ₂ -95% air atmosphere, was added to the medium above sporophyll polysaccharide at various concentrations, further Culture was performed. Collect the cells suspended in the medium and remove the remaining cells adhered to the Petri dish to trypsin.
Collected by / EDTA treatment and combined. The collected cells are washed with PBS (-), and RNase (1 mg / ml)
Processing was performed at 37 ° C. for 40 minutes with 40 μl / sample. PB
After washing twice with S (-), propidium iodide (25 μl)
(g / ml) and stained on ice for 30 minutes with 100 μl / sample. The cells were passed through a 70 μm nylon mesh once, and the DNA fragmentation rate of the cells was quantified and evaluated using a flow cytometer (Bechman Coulter E picsXL-2). Table 1 shows the results.

[0026]

[Table 1]

Mekabu polysaccharide was found to have the ability to induce apoptosis in a rat breast cancer cell line in a concentration and time dependent manner.

Example 3 Cell Selectivity of Mekabu Polysaccharide's Apoptosis Inducing Ability Two human breast cancer cell cultures (T47D and MDA-M
B231) and a normal human mammary gland cell line (MCF-10
The apoptosis-inducing ability of Mekabu polysaccharide (0.48 mg / ml) with respect to A) was examined in the same manner as in Example 2. Table 2 shows the results.

[0029]

[Table 2]

It was found that the Mekabu polysaccharide induces apoptosis in breast cancer cells but does not show apoptosis-inducing ability in normal breast cells.

Example 4 Comparison of Mekabu Polysaccharide and 5-Fluorouracil (5-FU) Apoptosis-Inducing Ability Mekabu polysaccharide (0.48 mg / ml) was compared with 5-FU (2 and 5-FU) which is most frequently used for the treatment of human breast cancer. 20 μg / m
The apoptosis-inducing ability of 1) against human breast cancer cell culture (T47D) was compared and examined. Table 3 shows the results.

[0032]

[Table 3]

As a result of comparison in each optimum concentration range,
Mekabu polysaccharide was found to have slightly stronger apoptotic ability than 5-FU. 5-FU is highly cytotoxic and cannot be used at higher concentrations.

Example 5 Fractionation of Mekabu Polysaccharide by Ultrafiltration and Analysis of Sugar Composition of Fractionated Purified Product Mekabu polysaccharide solution was subjected to ultrafiltration by a molecular weight of 100,000 or more (I), 100,000-50,000 (II), 550,000 (III) and 550,000 or less (IV). Using unseparated mekabu polysaccharide and fucoidan extracted from the same as control,
Comparative analysis of the sugar composition of each fractionated purified product was performed. Each of the fractions crystallized with ethanol was dissolved in reference water to prepare a sample. The analysis of constituent sugars is performed by the method of Reinhold [Reinhold, V.
N. (1972) Methods in Enzymolozy, 25B, 244-249]. The conditions of gas chromatography are as follows.

Gas chromatograph: Shimadzu GC14A Column: Capillary column (Shimadzu CBJ15, 0.32 mm ×
30 mm) Heating conditions: Starting temperature 180 ° C to 250 ° C at 5 ° C / min Carrier gas: Nitrogen gas Detector: Hydrogen flame ion detector Quantification: Shimadzu Integrator C-R6A Chromatopack

Neutral sugars can be determined by the phenol-sulfuric acid method [Duboi
s, M., Gilles, KA et al. (1956) Anal.Chem., 2
8, 350] using galactose as a standard.
For the determination of sulfate groups, the chondroitin sulfate C was used as a standard substance and the rhodisonic acid method [Terho, TT and Hartial
a, K. (1971) Anal. Biochem., 41, 471].
The results are shown in Tables 4 and 5.

[0037]

[Table 4]

[0038]

[Table 5]

Neutral sugars include fucose, galactose and mannose. If galactose is standard (1.0) without separation, the ratio of fucose to mannose is 1: 0.6, but that in fractions II, III, IV is 0.4 ± 0.1: 0.3 ± 0.05. The molar ratio of glucuronic acid is 0.1 with respect to 1 galactose in the unfractionated fraction, whereas the fractions of fractions II, III and IV are all as high as 1 to 0.6. Unidentified peaks X and Y with high contents were present in fractions II, III and IV. Retention time in gas chromatography (X: 11.9 minutes, Y: 1
3.1 minutes), it is likely that these are mannitol-like and inositol-like sugar alcohols. Therefore, the saccharide composition of the present polysaccharide is different from that of mekabufucoidan.

On the other hand, sulfuric acid (group) which is a feature of fucoidan
Is very low at about 1/50 of fucoidan in fractions II, III and IV, and is also characteristically different from mekabu fucoidan. The molar ratio of sulfate groups to neutral sugars of Mekabu polysaccharide was
V is about 1 (0.9 to 1.5), whereas Mekabufukoidan is about 2.

Example 6 Apoptosis Inducing Activity of Each Mekabu Polysaccharide Fraction The concentration of the sample was 0.48 mg / ml, and the treatment time was 96.
Apoptosis-inducing ability of human breast cancer cell lines (T47D, MDA-MB231, MCF-7) was evaluated in the same manner as in Example 2. The results are shown in FIG. Apoptosis-inducing ability is observed in all fractions, but higher apoptosis-inducing activity is recovered in fractions having a molecular weight of 100,000 or less than in unseparated fractions. 0.5 times higher effect.

Example 7 In Vivo Inhibitory Effect of Mekabu Polysaccharide on Carcinogenesis Forty-eight 8-week-old Sprague-Danley rats were intragastrically administered once with DMBA dissolved in olive oil at 20 mg / individual / 1 ml olive oil. One week later, the whole was arbitrarily divided into four groups (n = 12). Mekabu polysaccharide was placed in a 400 ml water bottle, and the stock solution (6 mg / ml) was taken (M-
A) A two-fold diluted solution (3 mg / ml) intake group (MB),
Free water was orally administered (administered) using water as a four-fold diluted solution (1.5 mg / ml) intake group (MC) and a control group (cont) using water. Water bottles are cleaned every two days,
After replacement, the intake was measured each time, and the intake was calculated every week. The weight change of each rat, the number of tumors in which breast cancer occurred by palpation, and the diameters of all tumors were measured every week for 32 weeks after DMBA administration. At the end of the experiment at week 32, blood was collected, the whole breast tumor was excised, and various organs were excised, and the weight and diameter of the breast tumor were measured.

The results are shown in FIGS. No difference in body weight change or intake was observed in each group, suggesting the safety of long-term intake of mekabu polysaccharide. While the control group had a breast cancer incidence of 100% at 13 weeks after DMBA administration,
The MA group was 100% at week 23, the MB group was 83.3% at week 32, and the MC group was 25% at week 32 at the end of the experiment.
In each case, a significantly higher carcinogenesis inhibitory effect was observed as compared with the control group (FIG. 2). In the comparison of the number of mammary tumors, the control group averaged 7.2 in the comparison at 32 weeks at the end of the experiment, whereas MA and M-
In the B and MC groups, 2.2, 1.1 and 0.3, respectively, significantly suppressed the occurrence of mammary tumors (FIG. 3). From the above results, it was revealed that Mekabu polysaccharide has an effect of suppressing the occurrence of breast cancer and the growth of breast cancer in the DMBA-induced breast cancer rat experimental system.

Example 8 Formulation Example Fraction II (molecular weight 1) of the aqueous extract of Mekabu obtained in Example 5
50,000 to 50,000), and dried to obtain a powder.
200 g of lactose is added to 00 g and mixed.
20% was added and kneaded. The kneaded product was granulated by a granulator, and then dried and tableted.

Example 9 Food Production Example (1) Production of Mekabu Candy Fraction II (molecular weight 1) of the water extract of Mekabu obtained in Example 5
0000-50,000), dried and powdered, using a conventional method,
Mekabu candy having the composition shown in Table 6 was produced.

[0046]

[Table 6]

Example 10 Food Production Example (2) Production of Mekabu Nutritional Capsules Mekabu water extract obtained in the same manner as in Example 1 (however,
After drying and pulverizing the powder (not subjected to ultrafiltration), capsules having the composition shown in Table 7 (tear-shaped soft capsules based on the gelatin formulation shown in Table 8) were produced.

[0048]

[Table 7]

[0049]

[Table 8]

[0050]

EFFECT OF THE INVENTION The apoptosis-inducing polysaccharide and the composition containing the apoptosis-inducing polysaccharide derived from seaweed water extract of the present invention can induce apoptosis selectively against abnormal cells that are undesirable for the living body. Is effective in preventing and treating diseases caused by In addition, the composition containing apoptosis-inducing polysaccharide and the apoptosis-inducing polysaccharide derived from the seaweed water extract has a very wide safety margin and can be taken orally on a daily basis. It is also useful as a material for foodstuffs such as food.

[Brief description of the drawings]

FIG. 1 is a graph showing the apoptosis-inducing activity of each fractionated purified product of Mekabu water extract against various human breast cancer cell cultures.

FIG. 2 is a graph showing changes over time in the incidence of breast cancer in a group of rats administered with various concentrations of mekabu polysaccharide and a group of rats not administered.

FIG. 3 is a graph showing the change over time in the average number of breast cancer tumors per rat in a group of rats administered with various concentrations of mekabu polysaccharide and a group of rats not administered.

FIG. 4 is a graph showing the average period until the onset of breast cancer in a rat group to which various concentrations of mekabu polysaccharide were administered and a rat group to which no concentration was administered.

FIG. 5 is a graph showing the average tumor weight at 32 weeks in a group of rats to which various concentrations of mekabu polysaccharide were administered and a group of rats to which no concentration was administered.

FIG. 6 is a graph showing the average tumor surface area at 32 weeks in a group of rats to which various concentrations of mekabu polysaccharide were administered and a group of rats to which no concentration was administered.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 37/00 A61P 37/00 43/00 105 43/00 105 (72) Inventor Akemi Hayakawa Kasugai City, Aichi Prefecture Ishiodai 1-1 Town Ishiodai 16-2 (72) Inventor Tomoyuki Yamada 2nd-23rd Nakano-cho, Kasugai-shi, Aichi 19F term (reference) 4C088 AA12 AA13 AA14 BA09 BA12 BA26 BA32 CA17 NA14 ZA01 ZB08 ZB21 ZB26 ZB33 ZC80 4C090 AA01 AA09 AA10 BA61 BB13 BB14 BB15 BB22 BB52 BC04 BC05 BC06 BD37 CA10 CA16 DA23 DA27

Claims (12)

[Claims] 1. A polysaccharide that selectively induces apoptosis of abnormal cells that are undesirable for a living body, comprising at least one fraction obtained by fractionating an aqueous extract of seaweed based on a difference in molecular weight. A composition comprising: 2. The composition according to claim 1, wherein the seaweed belongs to red algae or brown algae. 3. The composition according to claim 1, wherein the seaweed belongs to a family selected from the group consisting of the lycaenidae, the kelp family, the mozuku family and the fungi family. 4. An abnormal cell that is undesirable for a living body,
The composition according to any one of claims 1 to 3, wherein the composition is selected from the group consisting of cancer cells, autoreactive cells, abnormal nerve cells, virus-infected cells, and radiation-exposed cells. 5. A pharmaceutical composition comprising a pharmaceutically effective amount of a composition according to any one of claims 1 to 4, wherein
A pharmaceutical composition for the prevention and treatment of a disease selected from the group consisting of cancer, autoimmune disease, neurological disease, viral infection and radiation exposure disorder. 6. A food product comprising the composition according to claim 1. 7. A polysaccharide having the following properties and selectively inducing apoptosis to abnormal cells that are not desirable for a living body. (1) Molecular weight: 5,000-100,000 (2) Molar ratio of galactose, fucose, mannose is 1: 0.4 ± 0.1: 0.3 ± 0.05 (3) Glucuronic acid From 0.6 to galactose 1
Contains at a molar ratio of 1.0 8. A polymer having a molecular weight of 50,000 to 100,000.
The polysaccharide according to claim 7, which is 9. The polysaccharide according to claim 7, which is derived from seaweed. 10. The abnormal cell according to any one of claims 7 to 9, wherein the abnormal cell undesirable to the living body is selected from the group consisting of a cancer cell, an autoreactive cell, an abnormal nerve cell, a virus-infected cell and a radiation-exposed cell. Polysaccharide. 11. A pharmaceutical composition comprising the polysaccharide according to claim 7 as an active ingredient, selected from the group consisting of cancer, autoimmune diseases, neurological diseases, viral infections and radiation exposure disorders. A pharmaceutical composition for the prevention and treatment of a disease to be caused. A food product comprising the polysaccharide according to any one of claims 7 to 10.