JPWO2013080265A1 - Stabilization of S-adenosylmethionine by acidic sodium metaphosphate - Google Patents

Abstract

Providing a new method for the stabilization of S-adenosylmethionine. The present invention provides a food-drinking composition comprising S-adenosylmethionine and acidic sodium metaphosphate. The present invention also provides a method for producing a stable S-adenosylmethionine, which comprises a step of adding sodium acid metaphosphate to a composition containing the S-adenosylmethionine. The present invention further provides a method for stabilizing S-adenosylmethionine comprising the step of adding acidic sodium metaphosphate to a composition comprising said S-adenosylmethionine.

Description

  The present invention relates to the stabilization of S-adenosylmethionine with acidic sodium metaphosphate. The present invention particularly relates to a food-drinking composition comprising S-adenosylmethionine and acidic sodium metaphosphate. The invention also relates to a process for the production of stabilized S-adenosylmethionine.

  S-adenosylmethionine is present throughout the body and is a physiologically involved in many biological reactions as a methyl donor or enzyme activator in the synthesis and metabolism of hormones, neurotransmitters, phospholipids, and proteins. A compound. S-adenosylmethionine is metabolized by three metabolic pathways: methyl group transfer, sulfur group transfer, and aminopropyl group transfer.

  S-adenosylmethionine is reported to have useful effects on liver disorders such as cirrhosis, depression, arthritis, osteoarthritis, cartilage protection, Alzheimer's disease, peripheral neuropathy caused by HIV infection, or myelopathy. ing.

  However, since S-adenosylmethionine is a chemically unstable substance and rapidly decomposes even at room temperature, it is a major obstacle when used as a pharmaceutical or a supplement. So far, stabilization with a polyanion (for example, sodium hexametaphosphate) (Patent Document 1), stabilization with a phosphate compound (Patent Document 2), S-adenosylmethionine salts such as sulfate and p-toluenesulfonate Is suspended in an alcohol solvent (Patent Document 3), and is stabilized by an organic carboxylic acid and / or a compound having a chelate-forming ability (Patent Document 4), stabilized by phytic acid and cyclodextrin ( Patent document 5) has been reported.

JP-A-61-189293 JP 2007-197346 A JP 2008-13509 A JP 2005-229812 A Japanese Patent No. 4,598,846

  The inventors have unexpectedly discovered that by using acidic sodium metaphosphate, significant stabilization of S-adenosylmethionine is achieved compared to the previously known stabilization by sodium metaphosphate. The present invention has been completed. It has not been known in the past that superior stabilization of S-adenosylmethionine is achieved by using acidic sodium metaphosphate as compared to using sodium metaphosphate. Furthermore, as described in Examples 1 and 2 below, when sodium metaphosphate was used for stabilizing S-adenosylmethionine under acidic conditions, no significant stabilizing effect was observed. Considering these facts, it is unexpected that a remarkable stabilization effect can be obtained by using acidic sodium metaphosphate instead of sodium metaphosphate.

  In one aspect, the present invention provides a food-drinking composition comprising S-adenosylmethionine and acidic sodium metaphosphate.

  In one embodiment, the composition of the present invention contains the acidic sodium metaphosphate at a concentration of 2.5 times or more the S-adenosylmethionine.

  In another embodiment, the composition of the present invention comprises the sodium acid metaphosphate at a concentration of 2.5 to 10 times that of the S-adenosylmethionine.

  In another embodiment, the composition of the present invention comprises the sodium acid metaphosphate at a concentration of 2.5 to 7.5 times that of the S-adenosylmethionine.

  In another embodiment, the composition of the present invention comprises the sodium acid metaphosphate at a concentration of 5 to 7.5 times the S-adenosylmethionine.

  In another aspect, the present invention provides a pharmaceutical composition comprising S-adenosylmethionine and acidic sodium metaphosphate.

  In one embodiment, the pharmaceutical composition of the present invention contains the acidic sodium metaphosphate at a concentration of 2.5 times or more the S-adenosylmethionine.

  In another embodiment, the pharmaceutical composition of the present invention comprises the acidic sodium metaphosphate at a concentration of 2.5 to 10 times that of the S-adenosylmethionine.

  In another embodiment, the pharmaceutical composition of the present invention contains the acidic sodium metaphosphate at a concentration of 2.5 to 7.5 times that of the S-adenosylmethionine.

  In another embodiment, the pharmaceutical composition of the present invention comprises the acidic sodium metaphosphate at a concentration of 5 to 7.5 times the S-adenosylmethionine.

  In another embodiment, the pharmaceutical composition of the invention is for the treatment of depression or arthritis.

  In another aspect, the present invention provides a method for producing a stable S-adenosylmethionine, which comprises a step of adding sodium acid metaphosphate to a composition containing the S-adenosylmethionine. provide.

  In one embodiment, in the method, the acidic sodium metaphosphate is added at a concentration of 2.5 times or more the S-adenosylmethionine.

  In another embodiment, in the method, the acidic sodium metaphosphate is added at a concentration of 2.5 to 10 times that of the S-adenosylmethionine.

  In another embodiment, in the method, the acidic sodium metaphosphate is added at a concentration of 2.5 to 7.5 times the S-adenosylmethionine.

  In another embodiment, in the method, the acidic sodium metaphosphate is added at a concentration of 5 to 7.5 times the S-adenosylmethionine.

  In another embodiment, the production method of the present invention further includes a step of drying a mixture containing the S-adenosylmethionine and the acidic sodium metaphosphate.

  In another aspect, the present invention provides a method for stabilizing S-adenosylmethionine comprising the step of adding sodium acid metaphosphate to a composition comprising the S-adenosylmethionine. .

  In one embodiment, in the method, the acidic sodium metaphosphate is added at a concentration of 2.5 times or more the S-adenosylmethionine.

  In another embodiment, in the method, the acidic sodium metaphosphate is added at a concentration of 2.5 to 10 times that of the S-adenosylmethionine.

  In another embodiment, in the method, the acidic sodium metaphosphate is added at a concentration of 2.5 to 7.5 times the S-adenosylmethionine.

  In another embodiment, in the method, the acidic sodium metaphosphate is added at a concentration of 5 to 7.5 times the S-adenosylmethionine.

  A novel method for stabilizing S-adenosylmethionine is provided. According to the present invention, S-adenosylmethionine having excellent efficacy as a health food, a pharmaceutical composition, a dietary supplement, and the like can be supplied to consumers in a more stable state.

FIG. 1 shows sodium pyrophosphate, sodium polyphosphate, sodium metaphosphate, sodium pyrophosphate under acidic conditions, sodium polyphosphate under acidic conditions, and sodium metaphosphate under acidic conditions as stabilizers. -It is a graph which shows the residual degree (%) of S-adenosyl methionine with respect to the number of days in an acceleration test machine at the time of adding to adenosyl methionine. The vertical axis represents the residual rate (%) of S-adenosylmethionine, and the horizontal axis represents the number of days (days) in the acceleration tester. FIG. 2 shows an acceleration test machine in which 10-fold, 7.5-fold, 5-fold and 2.5-fold amounts of acidic sodium metaphosphate were added to S-adenosylmethionine as a stabilizer, respectively. It is a graph which shows the residual degree (%) of S-adenosyl methionine with respect to the number of days. The vertical axis represents the residual rate (%) of S-adenosylmethionine, and the horizontal axis represents the number of days (days) in the acceleration tester. FIG. 3 shows “A. Sodium acidic hexametaphosphate manufactured by Rin Kagaku Co., Ltd. (Toyama, Japan)”, “B. New Fcillin Sun F manufactured by F.C. Chemicals Co., Ltd. (Osaka, Japan)”, “C. Organo” “Polylinsan 1-G” manufactured by Foodtech Co., Ltd. (Saitama, Japan), “D. Mascorin F-2 manufactured by Taiyo Chemical Industries, Ltd. (Tokyo, Japan)”, “E. Taihei Chemical Industrial Co., Ltd. (Japan, “Osaka) Ultraporin”, “F. Tallinsan U (registered trademark)” manufactured by Ueno Pharmaceutical Co., Ltd. (Osaka, Japan), “G. Ultrapolyphos manufactured by Polyphos Chemical Laboratory (Osaka, Japan)” , "H. Organofoodtech Co., Ltd. (Saitama, Japan)" and "I. (Comparative example) Yoneyama Chemical Co., Ltd. (Osaka, Japan) sodium metaphosphate" as stabilizers. As that It is a graph which shows the residual degree (%) of S-adenosyl methionine with respect to the number of days in an acceleration test machine when it adds to each S-adenosyl methionine. The vertical axis represents the residual rate (%) of S-adenosylmethionine, and the horizontal axis represents the number of days (days) in the acceleration tester. FIG. 4 shows the acidity of “A. Phosphorus Chemical Industry Co., Ltd. (Toyama, Japan), acid sodium hexametaphosphate, lot (11.05.21)”, “B. Phosphorus Chemical Industry Co., Ltd. (Toyama, Japan). "Sodium hexametaphosphate, lot (11.08.2)", "C. Lot (1) of Muscorin F-2 manufactured by Taiyo Chemical Co., Ltd. (Tokyo, Japan)", and "D. Taiyo Chemical Co., Ltd. ( Residual degree of S-adenosylmethionine with respect to the number of days in the acceleration test machine when “Lot (2) of Muscorin F-2 manufactured by Tokyo, Japan” was added as a stabilizer to S-adenosylmethionine, respectively ( %). The vertical axis represents the residual rate (%) of S-adenosylmethionine, and the horizontal axis represents the number of days (days) in the acceleration tester.

  The invention will now be described, by way of example, with reference to the accompanying drawings, where appropriate. Throughout this specification, it should be understood that the singular forms also include the plural concept unless specifically stated otherwise. In addition, it is to be understood that the terms used in the present specification are used in the meaning normally used in the art unless otherwise specified. Thus, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.

  The embodiments provided below are provided for a better understanding of the present invention, and the scope of the present invention should not be limited to the following description. It will be apparent to those skilled in the art that appropriate modifications can be made within the scope of the present invention with reference to the description in the present specification.

  The present invention provides a food-drinking composition and a pharmaceutical composition comprising S-adenosylmethionine and acidic sodium metaphosphate. In the case of using acidic sodium metaphosphate, it has not been conventionally known that excellent stabilization of S-adenosylmethionine is achieved compared to the case of using sodium metaphosphate. Furthermore, as described in Examples 1 and 2 below, when sodium metaphosphate was used for stabilizing S-adenosylmethionine under acidic conditions, no significant stabilizing effect was observed. Considering these facts, it is unexpected that a remarkable stabilization effect can be obtained by using acidic sodium metaphosphate instead of sodium metaphosphate.

(Definition)
In the present specification, “S-adenosylmethionine” is a substance having an average molecular weight of 399.447, also referred to as “AdoMet”. The chemical formula of S-adenosylmethionine is as follows.

In the present specification, “acidic sodium metaphosphate” is also referred to as acidic sodium hexametaphosphate, which is a polymer acidic condensed phosphorus obtained by melting a reaction product of phosphoric acid and less than an equimolar alkali and dehydrating and condensing it. An acid salt mixture of the general formula {Na _x H _y (PO ₃ ) _{x + y} } _n (x is an arbitrary number of 1 or more, y is an arbitrary number of 1 or more, and n is an arbitrary number of 2 or more The pH of which is 2.2 or less. Examples of the acidic sodium metaphosphate in the present invention include, but are not limited to, acidic sodium metaphosphate for food additives, acidic sodium metaphosphate for quasi-drug raw materials, and / or industrial acidic sodium metaphosphate.

  In this specification, the pH of acidic sodium metaphosphate refers to the pH in a 1 w / v% solution of acidic sodium metaphosphate. The pH measurement can be performed by any method known in the art.

The acidic sodium metaphosphate of the present invention can be defined as follows.
- content: those present product (acidic sodium metaphosphate) dried comprises 60.0% ～83.0% as phosphorus pentoxide _{(P 2 O 5 = 141.94)} .
-Property: This product is a white fibrous crystal or powder or a piece or lump on non-white glass.
-Confirmation test (1) This product exhibits a sodium salt reaction.
・ Purity test (1) Liquid colorless, slightly turbid (powder 1.0 g, water 20 ml)
(2) Chloride Less than 0.21% as Cl (powder 0.10 g, comparative solution 0.01 N hydrochloric acid 0.60 ml)
(3) Normal Phosphate When 1.0 g of powder of this product is weighed and 2-3 drops of silver nitrate solution (1 → 50) is added, no significant yellow color is exhibited. “1 → 50” means that 1 mL of a silver nitrate solution (0.1 mol / L) is diluted to 50 mL.
(4) less 0.048% as the sulphate SO _4.
(5) Heavy metal Pb is 20 μg or less.
(6) Arsenic As ₂ O ₃ is 4.0 μg / g or less.
-Loss on drying 5.0% or less.

  The above standards are defined in the section of sodium metaphosphate in the 8th edition of the Food Additives Official Document.

  In the present specification, when the concentration of a specific substance is indicated, the “concentration of X-fold amount of S-adenosylmethionine” refers to the concentration (w / v) of S-adenosylmethionine in a certain composition. , Meaning that the concentration (w / v) of that particular substance is X times. For example, in a composition, when “sodium acid metaphosphate is contained at a concentration 5 times that of S-adenosylmethionine”, the acid sodium metaphosphate is 5 times the concentration (w / v) of S-adenosylmethionine. In the composition (w / v).

  In this specification, the “degree of polymerization” of acidic sodium metaphosphate refers to the average degree of polymerization (number average degree of polymerization) per molecule of acidic sodium metaphosphate.

  In the present specification, “stabilization” of S-adenosylmethionine refers to an effect of suppressing the degradation of unstable S-adenosylmethionine. More specifically, “stabilization” of S-adenosylmethionine in the present specification means that the residual amount of S-adenosylmethionine increases significantly after a certain period of time as compared to untreated ones. Say.

  In this specification, “a composition for eating and drinking” refers to a composition used for eating and drinking, and examples thereof include, but are not limited to, health foods, dietary supplements, and supplements. The edible composition of the present invention refers to any product containing stabilized S-adenosylmethionine. The composition for eating and drinking of the present invention is typically S-adenosylmethionine for liver disorders such as cirrhosis, depression, arthritis, osteoarthritis, cartilage protection, Alzheimer's disease, peripheral neuropathy caused by HIV infection or myelopathy. Displayed useful effects for sale. The food and drink composition of the present invention may be a food and drink supplement.

  The “health food” or “nutritional supplement” in the present invention refers to a food containing a component necessary for the body, or a component useful for maintaining / promoting health and having a physiological function. In the present invention, this component is S-adenosylmethionine, but other examples include vitamins, minerals, amino acids, coenzyme Q10, L-carnitine, brewer's yeast, ginseng extract and the like. In the present invention, the terms “nutritional supplement” and “health food” are used interchangeably and are not particularly strictly distinguished.

  In the present specification, the “food supplement” refers to any substance that can be added to any food or drink and can impart desirable characteristics to the food or drink. The food and drink supplement of the present invention refers to any product containing stabilized S-adenosylmethionine. Preferred properties of the food and drink supplement of the present invention include, for example, effects on liver disorders such as cirrhosis, depression, arthritis, osteoarthritis, cartilage protection, Alzheimer's disease, peripheral neuropathy caused by HIV infection, or myelopathy. However, it is not limited to these.

(Description of Preferred Embodiment)
The description of the preferred embodiment is described below, but it should be understood that this embodiment is an illustration of the present invention and that the scope of the present invention is not limited to such a preferred embodiment. It should be understood that those skilled in the art can easily make modifications, changes and the like within the scope of the present invention with reference to the following preferred embodiments.

The composition of the present invention has a longer period of time (eg, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, compared to a composition comprising conventional S-adenosylmethionine. About 60% or more, about 65% or more, about 70% or more, about 75% or more, about 80% or more, about 85% of S-adenosylmethionine immediately after preparation. More than about 90%, more than about 95%, or about 100% of S-adenosylmethionine. In a preferred embodiment, the composition of the present invention comprises about 80% or more of S-adenosylmethionine as prepared immediately after about 30 days in an accelerated tester, preferably about 40% in an accelerated tester. About 80% or more of S-adenosylmethionine immediately after preparation, more preferably about 80% or more of S-adenosylmethionine immediately after preparation in about 60 days in an accelerated tester. -Contains adenosylmethionine.

  The composition of the present invention may be a powder obtained by drying a mixture comprising S-adenosylmethionine and acidic sodium metaphosphate. This drying can be performed, for example, by freeze drying or spray drying. For example, drying in the present invention can be accomplished by lyophilization for about 3 days or longer. Drying in the present invention can also be accomplished by spray drying until a desired amount of powdering is achieved at an inlet temperature of 120-230 ° C and an outlet temperature of 100 ° C-70 ° C.

  The composition for eating and drinking of the present invention has a useful effect on liver disorders such as cirrhosis, depression, arthritis, osteoarthritis, cartilage protection, Alzheimer's disease, peripheral neuropathy caused by HIV infection or myelopathy. Can do. The composition for eating and drinking of the present invention can be a food and drink supplement.

(Eating and drinking composition of the present invention)
The composition of the present invention may be a composition for eating and drinking (including nutritional supplements and health foods).

  The dietary composition of the present invention includes health foods (specific health foods, functional nutritional foods), nutritional supplements (supplements), food additives, food supplements, and the like. Typically, the composition for eating and drinking of the present invention is a powder obtained by drying a mixture of S-adenosylmethionine and acidic sodium metaphosphate. The composition for eating and drinking of the present invention may include a yeast that produces S-adenosylmethionine. The powdered food and beverage composition of the present invention may be ingested by being added to other foods as a food additive or food supplement, or the powdered food and beverage composition of the present invention itself is a health food or It may be taken alone as a dietary supplement (supplement) or the like. The composition of the present invention may be processed into pellets, tablets, granules, etc. together with excipients such as dextrin, lactose, starch and the like, fragrances, pigments, etc., as necessary, and coated with gelatin or the like to be processed into capsules. May be. The compositions of the present invention are particularly suitable for use as health foods or dietary supplements. Typically, the edible composition of the present invention comprises about 3 g or more S-adenosylmethionine per 100 g.

  The amount of S-adenosylmethionine in the composition for eating and drinking according to the present invention is difficult to define uniformly depending on the type and condition of the food, but is 10 to 5000 mg / meal, preferably S-adenosylmethionine content. 100-1000 mg / meal and about 10-100% (preferably 30-100%, more preferably 50-100%, even more preferably 80-100%) in the case of supplements, beverages or general foods Etc., it may be about 0.01% or less.

  The composition for eating and drinking of the present invention is blended with excipients or additives usually used in foods, tablets, tablets, pills, granules, powders, powders, capsules, wettable powders, emulsions, liquids. , Extract, or elixir. Common excipients used in food include syrup, gum arabic, sucrose, lactose, powdered reduced maltose, cellulose sugar, mannitol, maltitol, dextran, starches, gelatin, sorbit, tragacanth, polyvinylpyrrolidone Agents; sucrose fatty acid esters, glycerin fatty acid esters, magnesium stearate, calcium stearate, talc, polyethylene glycol, etc .; disintegrants such as potato starch; wetting agents such as sodium lauryl sulfate. Examples of additives include fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, and the like.

(Pharmaceutical composition of the present invention)
The composition of the present invention may be a pharmaceutical composition (including veterinary drugs).

  The pharmaceutical preparation of the composition of the present invention (hereinafter referred to as the pharmaceutical composition of the present invention) may be an oral administration preparation or a parenteral administration preparation. The pharmaceutical composition of the present invention may be a solid preparation or a liquid preparation.

  Examples of solid preparations include powders, granules, tablets, tablets, pills, capsules, chewable agents, and the like, and examples of liquid preparations include emulsions, solutions, syrups and the like. The pharmaceutical composition of the present invention comprises about 3 g or more S-adenosylmethionine per 100 g.

  A solid preparation can be prepared by blending a pharmaceutically acceptable carrier or additive with S-adenosylmethionine of the present invention and sodium acid metaphosphate as active ingredients. For example, excipients such as sucrose, lactose, glucose, starch, mannitol; binders such as gum arabic, gelatin, crystalline cellulose, hydroxypropylcellulose, methylcellulose; disintegrants such as carmellose, starch; anhydrous citric acid Stabilizers such as sodium laurate, glycerol, and the like can be formulated for the formulation of the pharmaceutical composition of the present invention. Furthermore, the pharmaceutical composition of the present invention may be coated or encapsulated with gelatin, sucrose, gum arabic, carnauba wax and the like.

  A liquid formulation can be prepared by, for example, dissolving or dispersing the active ingredients S-adenosylmethionine of the present invention and acidic sodium metaphosphate in water, ethanol, glycerin, syrup, or a mixture thereof. The pharmaceutical composition of the present invention may further contain additives such as sweeteners, preservatives, demulcents, lubricants, diluents, buffers, or coloring agents.

  The parenteral preparation may be any parenteral preparation known to those skilled in the art. Examples of parenteral preparations for the pharmaceutical composition of the present invention include, but are not limited to, creams, sprays, gels, ointments, salves and the like. Pharmaceutical compositions comprising S-adenosylmethionine of the present invention and acidic sodium metaphosphate can also be injected directly into bandages, gauze, or patches (eg, soaked and dried), which are then topically applied. Can be applied.

  Techniques for formulating and administering pharmaceutical compositions of the present invention can be found, for example, in REMINGTON'S PHARMACEUTICAL SCIENCES (Mack Publishing Co., Easton, Pa.).

  Effective amounts and methods of administration of the pharmaceutical compositions of the invention can vary depending on the method of administration, the condition being treated and the severity of the condition being treated. The ordinary physician or veterinarian can readily determine the effective amount and method of administration of the pharmaceutical composition of the present invention.

(Acid sodium metaphosphate)
Sodium metaphosphate is a general term for a condensed phosphate obtained by melting an equimolar reaction product of phosphoric acid (for example, P ₂ O ₅ ) and an alkali (for example, caustic soda or sodium carbonate) at a high temperature and subjecting it to dehydration condensation. In terms of molecular structure, it is not a single substance but a mixture of neutral condensed phosphates containing cyclic structures and long-chain structures.

In contrast, acidic sodium metaphosphate is obtained by melting a reaction product of phosphoric acid (for example, P ₂ O ₅ ) and less than an equivalent amount of alkali (for example, caustic soda or sodium carbonate) and dehydrating and condensing it. It is a mixture of acidic condensed phosphates of macromolecules, and different compositions can be obtained depending on the production conditions such as the molar ratio of raw materials and reaction temperature. It is characterized in that it contains a network that is not found in sex metaphosphate.

Both the sodium metaphosphate and acidic sodium metaphosphate can be produced by changing the charging ratio of phosphoric acid (for example, P ₂ O ₅ ) and alkali (for example, caustic soda or sodium carbonate), Such manufacturing methods are well known to those skilled in the art.
Both sodium metaphosphate and acidic sodium metaphosphate are food additives used as water retention agents or sequestering agents. Acidic sodium metaphosphate is often used when it is desired to make the final product more acidic, but no other difference in use and effectiveness in these two additives has been known.

In this specification, acidic sodium metaphosphate is represented by the formula: {Na _x H _y (PO ₃ ) _{x + y} } _n (x is an arbitrary number of 1 or more, y is an arbitrary number of 1 or more, and n is It is an arbitrary number of 2 or more).

  In an embodiment of the present invention, the pH of the acidic sodium metaphosphate used in the present invention is 2.2 or less.

In an embodiment of the present invention, the acidic sodium metaphosphate used in the present invention is represented by the formula: {Na _x H _y (PO ₃ ) _{x + y} } _n , where x and y are each a pH of acidic sodium metaphosphate. The number is 2.2 or less.

  In an embodiment of the present invention, the number average polymerization degree of acidic sodium metaphosphate used in the present invention is an arbitrary number of 2 or more, more preferably 10 to 300, still more preferably 10 to 23, typically. Is 14.

  Acidic sodium metaphosphate is manufactured and sold by a number of manufacturers. Commercially available acidic sodium metaphosphates include sodium acidic hexametaphosphate manufactured by Phosphorus Chemical Co., Ltd. (Toyama, Japan), New Fcillin Sun F manufactured by FC Chemical Co., Ltd. (Osaka, Japan), Organo Food Tech Co., Ltd. (Polylinsan 1-G manufactured by Saitama, Japan), Muscorin F-2 manufactured by Taiyo Chemical Co., Ltd. (Tokyo, Japan), Ultraporin manufactured by Taihei Chemical Industrial Co., Ltd. (Osaka, Japan), Ueno Pharmaceutical Co., Ltd. ( Examples include, but are not limited to, Tallinsan U (registered trademark) manufactured by Osaka, Japan and Ultrapolyphos manufactured by Polyphos Chemical Laboratory Co., Ltd. (Osaka, Japan).

(Pharmaceutical composition containing S-adenosylmethionine)
S-adenosylmethionine is well known to have a variety of pharmaceutical uses. For example, S-adenosylmethionine alleviates liver damage (eg, reduces mortality due to cirrhosis) (eg, Lieber CS. Role of S-adenosyl-L-methionine in the treatment of liver diseases. J Hepatol). 1999; 30: 1155-9; Williams R, Lieber CS. The role of SAMe in the treatment of liver disease. Drugs 1990; 40 (suppl): 1-2, Mato JM, eJaF. S-Adenosylationine in alcoholic liver cirrhosis: a random Ized, placebo-controlled, double-blind, multicenter clinical trial. See J Hepatol 1999; 30: 1081-9, etc.), have a therapeutic effect on depression (eg, Janicak PG, M , Et al.S-Adenosylmethionine: a literature review and premier report.Ala J Med Sci 1988; 25: 306-13; in liv . Er dysfunction and affective disorders in relation to its physiological role in cell metabolism Drugs 1989; 38:.. 389-416; Bressa GM S-Adenosyl-L-methionine (SAMe) as antidepressant: meta-analysis of clinical studies Acta Neurol Scand 1994; 154: 7-14, etc.) and useful for the treatment of arthritis (see, for example, Bradley JD, Flosser D, Katz BP, et al. A-randomized, double-blind, placebo-controlled triof of intravenous loading with S-adenosyltherthene te te te r a te s a te s a ti s e s ed a s ti s e n a ti s e n a ti s e n a ti s e n a s (i) s ａｄ ｂ ｂ ｂ ｂ. J Rheumatol 1994; 21: 905-11; Padova C.I. S-Adenosylationine in the treatment of osteoarthritis: review of the clinical studies. Am J Med 1987; 83: 60-5), can improve Alzheimer's disease (eg, Morison, L.D., Smith, D.D., and Kish, S.J., Brain S). -Adenoylmethionine levels are gradually developed in Alzheimer's disease. See J. Neurochem., 67, 1328-1331 (1996), may improve peripheral neuropathy or myelopathy due to HIV infection, eg N , Trimble KC, Mulcahy F, Scott JM, Weir DG, Evidence of brain methyltransferase inhibition and earl . Brain involvement in HIV-positive patients Lancet, 337, 935-939, (1991);. Suretees R, Hyland K, Smith I., Central nervous system methyl-group metabolism in children with neurological complications of HIV infection Lancet, 335, 619-621, (1990); Castagna A, Le Grazie C, Accordini A, Giulidri P, Cavalli G, Bottiglieri T, Lazzarin A., Crebrospinal fluid S-adden. Ethionine (SAMe) and glutation contentions in HIV effect: see, for example, of of parental treatment with SAMe., Neurology, 45, 1678-1683 (1995).

  In this specification, depression typically refers to psychotic depression.

(Production of the composition of the present invention)
In a preferred embodiment, the composition of the present invention is produced by culturing yeast having the ability to produce S-adenosylmethionine, producing S-adenosylmethionine, and adding acidic sodium metaphosphate to the yeast culture medium. Is done. This yeast is preferably the yeast Saccharomyces cerevisiae K-7 strain (Sake Yeast Association No. 7). The addition of acidic sodium metaphosphate to the yeast culture medium may be performed during the culture of the yeast or may be performed after the culture. Preferably, after the yeast is cultured to produce S-adenosylmethionine, the culture solution is removed to obtain a concentrated yeast cell concentrate, and acidic sodium metaphosphate is added to the concentrated solution. This yeast cell concentrate is obtained by centrifuging the culture (for example, 8,000 rpm), removing the supernatant, collecting the cells, and adding an appropriate amount of the supernatant removed to the collected cells, It can be prepared by preparing a bacterial cell concentrate.

  In another embodiment, the composition of the present invention purifies S-adenosylmethionine produced by or produced in yeast as described above and against the purified S-adenosylmethionine. Alternatively, it may be produced by adding acidic sodium metaphosphate to chemically synthesized S-adenosylmethionine. Methods for purifying S-adenosylmethionine are well known in the art. Purification of S-adenosylmethionine in the present invention can be accomplished by any method that increases the concentration of S-adenosylmethionine. As an example, the purification of S-adenosylmethionine in the present invention can be achieved by concentrating and crystallizing an extract obtained by freezing and thawing yeast cells that produced S-adenosylmethionine. obtain. Concentration of the S-adenosylmethionine extract can be performed by methods well known to those skilled in the art that can achieve enrichment of S-adenosylmethionine. Examples of the concentration method include, but are not limited to, a combination of adsorption by a synthetic resin or cation exchange resin and concentration by reverse dialysis. Adsorbents that can be used for concentration of S-adenosylmethionine include, but are not limited to, synthetic resins (eg, synthetic resin Sepabeads SP-200 (Mitsubishi Chemical Corporation, Tokyo, Japan)). Examples of ion exchange resins that can be used for the concentration of S-adenosylmethionine include weakly acidic cation exchange resins (for example, Amberlite IRC-50 (Organo Corporation, Tokyo, Japan)). It is not limited. Reverse dialysis for concentration of S-adenosylmethionine includes dialysis using a reverse osmosis membrane (for example, reverse osmosis Reverse Osmosis (RO): product name Romenbra (Toray Industries, Inc., Tokyo, Japan)). It is not limited to this. Crystallization of the S-adenosylmethionine concentrate can be performed by using, for example, an acetone-methanol solvent, but is not limited thereto.

  In certain embodiments, after adding acidic sodium metaphosphate to a concentrate containing yeast that produced S-adenosylmethionine, the mixture may be dried. Examples of the drying method include, but are not limited to, freeze drying, spray drying, and reduced pressure drying. As the drying method in the present invention, freeze-drying is preferred. In certain embodiments, the mixture can be dried at −80 ° C. overnight and lyophilized for 72 h.

  The carbon source used when culturing the yeast is not particularly limited as long as the yeast can assimilate, for example, carbohydrates such as glucose, sucrose, starch, and molasses, alcohols such as ethanol, acetic acid, etc. The organic acid is mentioned. The nitrogen source is not particularly limited as long as the yeast to be used can assimilate, and includes, for example, inorganic nitrogen compounds such as ammonia, nitric acid, urea, or organic nitrogen compounds such as yeast extract and malt extract. Can be mentioned. Moreover, as inorganic salts, salts of phosphoric acid, potassium, sodium, magnesium, calcium, iron, zinc, manganese, cobalt, copper, molybdenum and the like can be used. Furthermore, methionine, adenine, and adenosylribonucleoside constituting the skeleton of S-adenosylmethionine can be added and cultured.

  The culture of the S-adenosylmethionine-producing yeast in the present invention can be carried out under either anaerobic conditions or aerobic conditions, but aerobic conditions are preferable in order to proliferate yeast cells efficiently. The culture temperature of the S-adenosylmethionine-producing yeast in the present invention is an arbitrary temperature within the range in which the yeast can grow, but the culture is preferably in the range of 15 to 40 ° C, and more preferably in the range of 25 to 35 ° C. . The pH during the culture of the S-adenosylmethionine-producing yeast in the present invention is an arbitrary pH within the range in which the yeast can grow, but the culture in the range of pH 3.5 to 8.0 is preferred, and the pH is 4.0 to 4.0. A range of 6.5 is more preferred. In addition, the culture method and culture conditions for S-adenosylmethionine-producing yeast in the present invention can be appropriately determined by those skilled in the art according to general yeast culture methods or culture conditions. In a specific embodiment, the yeast is used in a 5 L jar fermenter (feed medium amount: 3 L), a culture temperature of 28 ° C., a stirring speed of 500 rpm, a culture time of 36 to 48 h, an aeration rate of 0.5 VVM, a medium composition (w / 100 mL): cultured under conditions of 5% glucose, 0.75% yeast extract, 2.0% peptone, and 0.15% methionine.

  References such as scientific literature, patents and patent applications cited herein are hereby incorporated by reference in their entirety to the same extent as if each was specifically described.

  The present invention has been described with reference to the preferred embodiments for easy understanding. In the following, the present invention will be described based on examples, but the above description and the following examples are provided only for the purpose of illustration, not for the purpose of limiting the present invention. Accordingly, the scope of the present invention is not limited to the embodiments or examples specifically described in this specification, but is limited only by the scope of the claims.

(Example 1. Examination of stabilization effect of various phosphate compounds and influence of acid treatment)
In this example, the stabilizing effect of sodium polyphosphate and sodium metaphosphate, which are phosphoric acid compounds conventionally known to stabilize S-adenosylmethionine, was confirmed.

Using yeast Saccharomyces cerevisiae K-7 strain (Sake Yeast Association No. 7), 5 L jar fermenter (feeding medium amount: 3 L), culture temperature 28 ° C., stirring speed 500 rpm, culture time 36-48 h, aeration rate 0. 5 VVM, medium composition (w / 100 mL): cultured with glucose 5%, yeast extract 0.75%, peptone 2.0%, methionine 0.15%. The culture was centrifuged (8,000 rpm), the supernatant was removed, and the cells were collected. An appropriate amount of the supernatant liquid removed from the recovered cells was added to prepare a cell concentrate. The concentration of S-adenosylmethionine in the concentrate was measured and sodium pyrophosphate (Na ₄ P ₂ O ₇ : tetrasodium pyrophosphate (crystal / anhydrous) manufactured by Taiyo Chemical Industries, Tokyo, Japan), polyphosphorus Sodium phosphate (Na ₅ P ₃ O ₁₀ : sodium tripolyphosphate manufactured by Taiyo Chemical Co., Ltd., Tokyo, Japan) and sodium metaphosphate ((NaPO ₃ ) _n : Taiyo Chemical Co., Ltd. (Tokyo, Japan) (Sodium hexametaphosphate) was added to the cell concentrate so as to be 4 times the amount of S-adenosylmethionine. The prepared sample was frozen at −80 ° C. overnight. Lyophilization was performed for 72 hours to prepare yeast powder. The yeast powder was packed in an aluminum pouch and stored in an acceleration tester (Advantec, model THE051FA) (40 ° C., humidity 75%). One day storage of the accelerated testing machine under these conditions corresponds to six days of room temperature storage. The yeast powder was sampled regularly and S-adenosylmethionine was extracted using perchloric acid. Specifically, 1 mL of 10% perchloric acid was added to 0.02 g of yeast powder, extraction was performed for 1 hour, and the supernatant (extract) was collected by centrifugation (10,000 rpm, 10 minutes). For the measurement of S-adenosylmethionine, UPLC (Waters, model TUV) was used, and the extract was analyzed by a gradient of 0.1% formic acid + 5 mM sodium nonanesulfonate and acetonitrile. The column used was UK-C18 (Intact Corporation (Tokyo, Japan); 4.6 × 250 mm, 3 μm). The results are shown in Table 1 below. Note that the results are shown as relative values, with the value at the time of preparation of each sample being 100%.

  Table 1. Stabilization effect by various phosphate compounds

  As shown in Table 1, compared to S-adenosylmethionine without addition of a stabilizer, in S-adenosylmethionine to which sodium pyrophosphate, sodium polyphosphate or sodium metaphosphate was added as a stabilizer, Some improvement in stability was observed. However, since this improvement in stability is considered insufficient, a more efficient stabilization method was investigated.

  The composition containing the above S-adenosylmethionine and sodium pyrophosphate, sodium polyphosphate, or sodium metaphosphate exhibits alkalinity. In order to investigate the effect of pH on the stabilization of S-adenosylmethionine, stabilization of S-adenosylmethionine with sodium pyrophosphate, sodium polyphosphate or sodium metaphosphate was carried out under acidic conditions. We verified the degree of. The acid treatment was performed by adding various phosphoric acid compounds in 4 times the amount of S-adenosylmethionine and then adjusting the pH to 1 with 78% sulfuric acid.

Specifically, using a yeast Saccharomyces cerevisiae K-7 strain (Sake Yeast Association No. 7), a 5 L jar fermenter (feeding medium amount: 3 L), a culture temperature of 28 ° C., a stirring speed of 500 rpm, and a culture time of 36 to 48 h. Aeration rate 0.5 VVM, medium composition (w / 100 mL): Glucose 5%, yeast extract 0.75%, peptone 2.0%, methionine 0.15%. The culture was centrifuged (8,000 rpm), the supernatant was removed, and the cells were collected. An appropriate amount of the supernatant liquid removed from the recovered cells was added to prepare a cell concentrate. The concentration of S-adenosylmethionine in the concentrate was measured and sodium pyrophosphate (Na ₄ P ₂ O ₇ : tetrasodium pyrophosphate (crystal / anhydrous) manufactured by Taiyo Chemical Industries, Tokyo, Japan), polyphosphorus Sodium phosphate (Na ₅ P ₃ O ₁₀ : sodium tripolyphosphate manufactured by Taiyo Chemical Co., Ltd., Tokyo, Japan) and sodium metaphosphate ((NaPO ₃ ) _n : Taiyo Chemical Co., Ltd. (Tokyo, Japan) (Sodium hexametaphosphate) was added to the cell concentrate so as to be 4 times the amount of S-adenosylmethionine. 78% sulfuric acid was added to each sample, and the pH was adjusted to pH 1. The prepared sample was frozen at −80 ° C. overnight. Lyophilization was performed for 72 hours to prepare yeast powder. This yeast powder was packed in an aluminum pouch and stored in an accelerated tester (Advantec, model THE051FA) (40 ° C., humidity 75%). One day storage of the accelerated testing machine under these conditions corresponds to six days of room temperature storage. The yeast powder was sampled regularly and S-adenosylmethionine was extracted using perchloric acid. Specifically, 1 mL of 10% perchloric acid was added to 0.02 g of yeast powder, extraction was performed for 1 hour, and the supernatant (extract) was collected by centrifugation (10,000 rpm, 10 minutes). For the measurement of S-adenosylmethionine, UPLC (Waters, model TUV) was used, and the extract was analyzed by a gradient of 0.1% formic acid + 5 mM sodium nonanesulfonate and acetonitrile. The results are shown in Table 2 below. Note that the results are shown as relative values, with the value at the time of preparation of each sample being 100%.

  Table 2. Stabilization effect of various phosphate compounds under acidic conditions

  The results of Table 1 and Table 2 are summarized in FIG.

  From the above results, sodium pyrophosphate, sodium polyphosphate, and sodium metaphosphate provide a certain stabilizing effect compared to no addition, but they are insufficient and due to these substances under acidic conditions It was demonstrated that no significant improvement in stability was observed with stabilization.

(Example 2. Stabilization of S-adenosylmethionine by sodium acid metaphosphate)
In this example, the stabilizing effect of S-adenosylmethionine by acidic sodium metaphosphate was examined.

Using yeast Saccharomyces cerevisiae K-7 strain (Sake Yeast Association No. 7), 5 L jar fermenter (feeding medium amount: 3 L), culture temperature 28 ° C., stirring speed 500 rpm, culture time 36-48 h, aeration rate 0. 5 VVM, medium composition (w / 100 mL): cultured with glucose 5%, yeast extract 0.75%, peptone 2.0%, methionine 0.15%. The culture was centrifuged (8,000 rpm), the supernatant was removed, and the cells were collected. An appropriate amount of the supernatant liquid removed from the recovered cells was added to prepare a cell concentrate. The concentration of S-adenosylmethionine in the concentrated solution was measured, and acid sodium metaphosphate ({Na _x H _y (PO ₃ ) _{x + y} } _n (acid sodium hexametaphosphate manufactured by Phosphor Chemical Co., Ltd., Toyama, Japan)) , S-adenosylmethionine 2.5 times, 5 times, 7.5 times, and 10 times the amount were added to the cell concentrate. The yeast powder was packed in an aluminum pouch and stored in an accelerated tester (Advantec, model THE051FA) (40 ° C., 75% humidity). One day of storage of the accelerated test machine under these conditions corresponds to 6 days of storage at room temperature, sampling yeast powder regularly and extracting S-adenosylmethionine using perchloric acid. Specifically, 1 mL of 10% perchloric acid was added to 0.02 g of yeast powder, extraction was performed for 1 hour, and the supernatant (extract) was collected by centrifugation (10,000 rpm, 10 minutes). For the measurement of S-adenosylmethionine, UPLC (Waters, model TUV) was used, and the extract was analyzed by a gradient with 0.1% formic acid + 5 mM sodium nonanesulfonate and acetonitrile, and the results are shown in Table 3 below. The results are shown in Fig. 2. Note that the results are shown as relative values, with the value at the time of preparation of each sample being 100%.

  Table 3. Stabilization effect by sodium acid metaphosphate

  Surprisingly, unexpectedly significant stabilization of S-adenosylmethionine was achieved with acidic sodium metaphosphate. This stabilizing effect is observed at all tested concentrations of 2.5-fold to 10-fold, with more stabilization being achieved at concentrations of 2.5-fold to 7.5-fold, especially 5-fold. Significant stabilization was achieved at ˜7.5 times the concentration. In view of the results of Example 1 which showed that no significant stabilization was achieved by the addition of sodium metaphosphate or by addition of sodium metaphosphate under acidic conditions, the acidic metaphosphate demonstrated in Table 3 The remarkable stabilization of S-adenosylmethionine by sodium is completely unexpected.

  Moreover, since storage of the accelerated test machine 1 day under the above conditions corresponds to 6 days of normal temperature storage, from the results of Table 3, when S-adenosylmethionine added with acidic sodium metaphosphate was stored at normal temperature, It can be seen that about 75 to 90% remains stable even after about one year. This is useful in the application of S-adenosylmethionine to food and drink, nutritional supplement, pharmaceutical, herbal medicine or veterinary medicine.

(Example 3. S-adenosylmethionine stabilization effect by various acidic sodium metaphosphate products)
In this example, the difference in S-adenosylmethionine stabilizing effect was examined for various acidic sodium metaphosphate products from different manufacturers.

  Using yeast Saccharomyces cerevisiae K-7 strain (Sake Yeast Association No. 7), 5 L jar fermenter (feeding medium amount: 3 L), culture temperature 28 ° C., stirring speed 500 rpm, culture time 36-48 h, aeration rate 0. 5 VVM, medium composition (w / 100 mL): cultured with glucose 5%, yeast extract 0.75%, peptone 2.0%, methionine 0.15%. The culture was centrifuged (8,000 rpm), the supernatant was removed, and the cells were collected. An appropriate amount of the supernatant liquid removed from the recovered cells was added to prepare a cell concentrate. The concentration of S-adenosylmethionine in the concentrate was measured, and sodium hexametaphosphate manufactured by Phosphorus Chemical Industries (Toyama, Japan), New Fcillin Sun F, Organofood manufactured by FC Chemical (Osaka, Japan) Polyrinsan 1-G manufactured by Tech Co., Ltd. (Saitama, Japan), Muscorin F-2 manufactured by Taiyo Chemical Co., Ltd. (Tokyo, Japan), Ultraporin manufactured by Taihei Chemical Industrial Co., Ltd. (Osaka, Japan), Ueno Pharmaceutical Tallinsan U (registered trademark) manufactured by Osaka Co., Ltd. (Osaka, Japan) or Ultrapolyphos produced by Polyphos Chemical Laboratory Co., Ltd. (Osaka, Japan) is used so that the amount is 4 times that of S-adenosylmethionine. Added to body concentrate. In addition, as a comparative example, sodium metaphosphate (polyphosphate sun 5-B manufactured by Organo Food Tech Co., Ltd. (Saitama, Japan) and sodium metaphosphate manufactured by Yoneyama Chemical Co., Ltd. (Osaka, Japan)) each in 4 times the amount. It added to the microbial cell concentrate so that it might become. The prepared sample was frozen at −80 ° C. overnight. Lyophilization was performed for 72 hours to prepare yeast powder. This yeast powder was packed in an aluminum pouch and stored in an accelerated tester (Advantec, model THE051FA) (40 ° C., humidity 75%). One day storage of the accelerated testing machine under these conditions corresponds to six days of room temperature storage. The yeast powder was sampled regularly and S-adenosylmethionine was extracted using perchloric acid. Specifically, 1 mL of 10% perchloric acid was added to 0.02 g of yeast powder, extraction was performed for 1 hour, and the supernatant (extract) was collected by centrifugation (10,000 rpm, 10 minutes). For the measurement of S-adenosylmethionine, UPLC (Waters, model TUV) was used, and the extract was analyzed by a gradient of 0.1% formic acid + 5 mM sodium nonanesulfonate and acetonitrile. The results for each product are shown in Table 4 below and FIG. The correspondence between each item in the table below and the product is as follows.

A. Acid sodium hexametaphosphate manufactured by Phosphorus Chemical Industries, Ltd. (Toyama, Japan) New Fsilin Sun F manufactured by FSC Ltd. (Osaka, Japan)
C. Polylinsan 1-G manufactured by Organo Food Tech Co., Ltd. (Saitama, Japan)
D. Muscorin F-2 manufactured by Taiyo Chemical Industries (Tokyo, Japan)
E. Ultraporin manufactured by Taihei Chemical Industry Co., Ltd. (Osaka, Japan) Talinsan U (registered trademark) manufactured by Ueno Pharmaceutical Co., Ltd. (Osaka, Japan)
G. Ultra Polyphos H.P. manufactured by Polyphos Chemical Laboratory Co., Ltd. (Osaka, Japan) (Comparative example) Polyphosphorus 5-B manufactured by Organo Foodtech Co., Ltd. (Saitama, Japan)
I. (Comparative Example) Sodium metaphosphate manufactured by Yoneyama Chemical Co., Ltd. (Osaka, Japan) Note that the results are shown as relative values with the value at the time of preparation of each sample as 100%.

  Table 4. Stabilization of S-adenosylmethionine by various acidic sodium metaphosphate products

  It has been shown that excellent stabilization of S-adenosylmethionine is achieved by various acidic sodium metaphosphate products, although there are some variations from product to product.

(Example 4. Difference in S-adenosylmethionine stabilizing effect between lots of acidic sodium metaphosphate product)
In this example, the difference in stabilizing effect of S-adenosylmethionine among lots of acidic sodium metaphosphate products was examined.

  Using yeast Saccharomyces cerevisiae K-7 strain (Sake Yeast Association No. 7), 5 L jar fermenter (feeding medium amount: 3 L), culture temperature 28 ° C., stirring speed 500 rpm, culture time 36-48 h, aeration rate 0. 5 VVM, medium composition (w / 100 mL): cultured with glucose 5%, yeast extract 0.75%, peptone 2.0%, methionine 0.15%. The culture was centrifuged (8,000 rpm), the supernatant was removed, and the cells were collected. An appropriate amount of the supernatant liquid removed from the recovered cells was added to prepare a cell concentrate. The concentration of S-adenosylmethionine in the concentrate was measured, and sodium acid hexametaphosphate, lot “11.05.21” or “11.08.21” manufactured by Rin Kagaku Kogyo Co., Ltd. (Toyama, Japan) Lot “1” or “2” of Mascoline F-2 manufactured by Chemical Industry Co., Ltd. (Tokyo, Japan) was added to the bacterial cell concentrate so as to be 4 times the amount of S-adenosylmethionine. Four prepared samples were frozen overnight at -80 ° C. Lyophilization was performed for 72 hours to prepare yeast powder. This yeast powder was packed in an aluminum pouch and stored in an accelerated tester (Advantec, model THE051FA) (40 ° C., humidity 75%). One day storage of the accelerated testing machine under these conditions corresponds to six days of room temperature storage. The yeast powder was sampled regularly and S-adenosylmethionine was extracted using perchloric acid. Specifically, 1 mL of 10% perchloric acid was added to 0.02 g of yeast powder, extraction was performed for 1 hour, and the supernatant (extract) was collected by centrifugation (10,000 rpm, 10 minutes). For the measurement of S-adenosylmethionine, UPLC (Waters, model TUV) was used, and the extract was analyzed by a gradient of 0.1% formic acid + 5 mM sodium nonanesulfonate and acetonitrile. The results are shown in Table 5 below and FIG. The correspondence between each item in the table below and the product is as follows.

A. Acidic sodium hexametaphosphate, lot “11.05.21” manufactured by Phosphorus Chemical Industries, Ltd. (Toyama, Japan)
B. Sodium acid hexametaphosphate, lot "11.08.2", manufactured by Phosphorus Chemical Industries, Ltd. (Toyama, Japan)
C. Lot "1" of Muscorin F-2 manufactured by Taiyo Chemical Co., Ltd. (Tokyo, Japan)
D. Lot “2” of Muscorin F-2 manufactured by Taiyo Chemical Co., Ltd. (Tokyo, Japan)
Note that the results are shown as relative values with the value at the time of preparation of each sample as 100%.

  Table 5. Differences in S-adenosylmethionine stabilization effect between lots of acidic sodium metaphosphate products

  As is apparent from the results, no significant difference in S-adenosylmethionine stabilizing effect was found between lots of each product.

  As mentioned above, although this invention has been illustrated using preferable embodiment of this invention, this invention should not be limited and limited to this embodiment. It is understood that the scope of the present invention should be construed only by the claims. It is understood that those skilled in the art can implement an equivalent range based on the description of the present invention and the common general technical knowledge from the description of specific preferred embodiments of the present invention.

Claims (22)

A composition for eating and drinking comprising S-adenosylmethionine and sodium acid metaphosphate. The composition according to claim 1, comprising the acidic sodium metaphosphate at a concentration of 2.5 times or more the S-adenosylmethionine. The composition according to claim 1, comprising the acidic sodium metaphosphate in a concentration of 2.5 to 10 times that of the S-adenosylmethionine. The composition according to claim 1, comprising the acidic sodium metaphosphate in a concentration of 2.5 to 7.5 times that of the S-adenosylmethionine. The composition according to claim 1, comprising the acidic sodium metaphosphate in a concentration of 5 to 7.5 times the S-adenosylmethionine. A pharmaceutical composition comprising S-adenosylmethionine and acidic sodium metaphosphate. The pharmaceutical composition according to claim 6, comprising the acidic sodium metaphosphate in a concentration of 2.5 times or more the S-adenosylmethionine. The pharmaceutical composition according to claim 6, comprising the acidic sodium metaphosphate at a concentration of 2.5 to 10 times that of the S-adenosylmethionine. The pharmaceutical composition according to claim 6, comprising the acidic sodium metaphosphate at a concentration of 2.5 to 7.5 times that of the S-adenosylmethionine. The pharmaceutical composition according to claim 6, comprising the acidic sodium metaphosphate at a concentration of 5 to 7.5 times the S-adenosylmethionine. 7. A pharmaceutical composition according to claim 6 for the treatment of depression or arthritis. A method for producing a stable S-adenosylmethionine, comprising a step of adding sodium acid metaphosphate to a composition containing the S-adenosylmethionine. The production method according to claim 12, wherein the acidic sodium metaphosphate is added at a concentration of 2.5 times or more the S-adenosylmethionine. The production method according to claim 12, wherein the acidic sodium metaphosphate is added at a concentration of 2.5 to 10 times the amount of the S-adenosylmethionine. The production method according to claim 12, wherein the acidic sodium metaphosphate is added at a concentration of 2.5 to 7.5 times that of the S-adenosylmethionine. The production method according to claim 12, wherein the acidic sodium metaphosphate is added at a concentration of 5 to 7.5 times the S-adenosylmethionine. The manufacturing method of Claim 12 which further includes the process of drying the mixture containing the said S-adenosyl methionine and the said acidic sodium metaphosphate. A method for stabilizing S-adenosylmethionine, comprising the step of adding sodium acid metaphosphate to a composition comprising the S-adenosylmethionine. The method according to claim 18, wherein the acidic sodium metaphosphate is added at a concentration of 2.5 times or more the S-adenosylmethionine. The method according to claim 18, wherein the acidic sodium metaphosphate is added at a concentration of 2.5 to 10 times that of the S-adenosylmethionine. The method according to claim 18, wherein the acidic sodium metaphosphate is added at a concentration of 2.5 to 7.5 times that of the S-adenosylmethionine. The method according to claim 18, wherein the acidic sodium metaphosphate is added at a concentration of 5 to 7.5 times the S-adenosylmethionine.